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Nov 2016

Vol: 06 Issue: 03(12-28)

International Journal of Pharmaceutical Erudition

www.pharmaerudition.org Nov. 2016, 6(3), 12-28 12 | P a g e

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Review Article

Novel Drug Delivery System and Its Uses in the Treatment of Acne

Kiran Sirvi*, Pradeep K. Goyal , Bhupendra Vyas

B.N. Institute of pharmaceutical sciences, Udaipur (Rajasthan) 313001 India

Acne is a common inflammatory skin disease which affects the pilosebaceous units of the skin. It can havesevere psychological effects and can leave the patient with severe skin scarring. There are four well-recognized pathological factors responsible for acne which is also the target for acne therapy. In thisreview, different treatment options are discussed, including topical (i.e., retinoids, and antibiotics) andsystemic (i.e., retinoid, antibiotics, and hormonal) treatments. Since the general public has been shown anincreasing interest in more natural and generally safer treatment options, the use of complementary andalternative medicines (CAM) for treating acne was also discussed. The use of physical therapies such ascome done extraction, cryoslush therapy, cryotherapy, electrocauterization, intralesional corticosteroids andoptical treatments are also mentioned. Acne has been extensively researched with regards to the diseasemechanism as well as treatment options. However, due to the increasing resistance of Propioni bacteriumacnes towards the available antibiotics, there is a need for new treatment methods. Additionally, the lack ofnecessary evidence on the efficacy of CAM therapies makes it necessary for researchers to investigatethese treatment options further.

Keywords: Novel drug delivery system, Acne, Retinoids ,Tretinion, Adapalene and Benzoyl peroxide.

INTRODUCTIONAcne is a medical condition describing blockedskin pores that result in lesions. For a variety ofreasons that aren’t entirely understood, skinpores can become plugged with sebum, thenatural oil produced by skins sebaceous glands.Once plugged, dead cells and bacteria becometrapped in the pore, resulting in the lesionscommon to acne. The most common lesions arecalled ‘comedones’. Comedones come in twobasic varieties, ‘white heads’ and ‘black heads’. A

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white head is a plugged pore that has begun tobulge outward from the skin due to bacteria,dead skin cells, and other contaminants thathave become trapped inside.[1] The bulging domeshape often takes on a white appearance. Blackheads are simply comedones that have becomeopened, revealing the dark follicle plug within.Acne comedones are often referred to aspimplesor zits. Microcomedones are a lesscommon form of acne lesion, sometimes referredto as papules. These are basically smallcomedones that form from localized cellular

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reactions to the processes that cause acne.[2]

That usually occur in clusters and are sometimestoo small to see, but can be felt as a series oflittle bumps along the skin surface. In moresevere forms of acne, pustules, nodules andcysts can form. A pustule is like a normalcomedone, but larger due to a higher amount ofdead white cells, or pus, trapped inside theplugged sebaceous follicle. Nodules are a moresevere form of papules, extending deeper intothe skin tissue and resulting in large raisedlegions that are usually inflamed, and painful totouch. Cysts are very large fluid filled sacs thatcan result from pustules or nodules. Thoughnone of these forms of acne are dangerous or lifethreatening, they can leave scars and aresometimes very disfiguring. What causes theplugged pores that result in acne is a questionthat scientists and doctors still haven’t been ableto completely agree upon. Today, most theoriesseem to point to a combination of factors thatinclude genetics, hormone changes, and stress.For years it was believed that diet was a strongcomponent to acne, but most evidence todaysuggests that hormones and stress are morelikely to be the culprits.

CAUSE OF ACNEAcne develops as a result of blockages infollicles hyperkeratinization and formation of aplug of keratin and sebum (a microcomedo) is

the earliest change. Enlargement of sebaceousglands and an increase in sebum productionoccur with increased androgen (DHEA-S)production at adrenaeche. The micrcomedo mayenlarge to form an open comedone (blackhead)or close comedone (whitehead).[3] Whitehead arethe direct result of sebaceous gland becomingclogged with sebum ,a naturally occurring oil, anddead skin cells. In these condition the naturallylargely commensal bacteria propionobacteriumacnes can cause inflammation , leading toinflammatory lesion (papules, infected pustules,or nodules) in the dermis around themicrocomedo or comedone, which results inredness and may result in scarring or hyper-pigmentation.

Genetically- There is a much greater chancefor the children to have acne if their parents hadacne in their teenage years, as the genes carryinformation from the parents to children. Thisform of acne cannot be avoided until and unlessthe advancement of medical sciences leads tothe deletion of the culprit genes.

Hormonal- There is production of theandrogen hormones during the adulthood yearsand this hormone activates the stimulation of theoil producing glands in the skin and this leads tothe clogging of the pores and in turn results in thecausation of pimples and blackheads.

Stress- This is not a proven fact whether the




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stress causes the initiation and formation ofacne lesions, but this can surely aggravate theacne pimples and can also aggravate anycondition of the skin that you are suffering from

Diet- It is not surely known that the diet cancause the formation of acne pimples as is thecase with stress, but there are some experts whobelieve that the allergies to certain foods cancause the trigger of the acne problem in anindividual.

TREATMENTThe main goal of acne treatment is to control andtreat existing acne lesions, prevent permanentscarring as far as possible, limit the duration ofthe disorder and to minimize morbidity. Thepatient should be informed on the aims involvedin preventing new acne lesions while allowing theexisting ones to heal. Patients should also bemade aware that it may take 3–6 weeks until animprovement can be observed. [4] Individualpatient factors must be taken into account whendetermining a regimen for the treatment of acne.Some of these factors are the current medicalcondition, disease state, severity of the lesions,endocrine history and the preferred treatment ofthe patient.

Topical TreatmentTopical products have the advantage of beingapplied to the affected area directly; thus

decreasing systemic absorption and increasingthe exposure of the pilo-sebaceous units to thetreatment.[4] However, a major side effect oftopically applied anti-acne products is skinirritation. Preparations for topical application areavailable as various formulations, includingcreams, gels, lotions, solutions and washes.Topical therapy is based on the type and severityof acne. Mild acne is often treated with topicalretinoids, or a variety of diverse treatments suchas azelaic acid, salicylic acid and benzoylperoxide. Mild to moderate inflammatory acnecan be treated with topical anti-inflammatoryagents as well as topical antibiotics . Thedifferent topical anti-acne drugs target differentpathophysiological factors and a few of thecommon topical treatments will be discussedbelow.RetinoidsTopical retinoids can be used as mono therapy forinflammatory acne, in combination with moresevere forms of acne or as a maintenancetreatment. They generally control the formation ofmicrocomedones, reduce the formation of lesionsand existing comedones, decrease sebumproduction and normalize desquamation of theepithelium. They target the microcomedones andsuppress comedone formation. They may alsoshow anti-inflammatory properties. Gollnick andKrautheim gave the following suggestions on the




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use of topical retinoid: (1) the use of topicalretinoid is vital for maintenance treatment; (2)retinoids can repair the scarring andhyperpigmentation of the skin; (3) this class ofdrugs should be first choice of treatment for mostof the acne types; and (4) when combined withtopical antimicrobials it is more effective ininflammatory acne. A common side effect duringthe first few weeks of topical retinoid treatment isa flare up of acne. This should, however, clear asthe patient continues with the treatment . Onlysome of the most common topical retinoids (i.e.,tretinoin, adapalene and tazarotene) used in acnetreatment will be discussed.

TretinoinTretinoin is a form of vitamin A. It is a standardcomedolytic agent used in acne treatment toregularize desquamation of the epithelium, whichprevents blockage of pilosebaceous units. It alsoseems to have anti-inflammatory properties. Ithas been a topical treatment for acne for overthree decades.

AdapaleneAdapalene is a synthetic retinoid analogue whichis most commonly used as a first line topicalretinoid treatment for Acne vulgaris. It normalizesthe cell differentiation of the follicular epitheliumand prevents comedone formation. It also showsanti-inflammatory action on the acne lesions.Tazarotene

Tazarotene is a synthetic acetylenic pro-drugwhich is converted to tazarotenic acid inkeratinocytes. It is one of the newer retinoidsused for acne treatment. It affects thekeratinocyte differentiation and proliferation in theepithelial tissue and may also show anti-inflammatory properties . It is regarded as asecond line treatment after no response wasobserved after previous tretinoin or adapalenetreatment, as it may cause skin irritation in acnepatients.

Other RetinoidsOther retinoids used for topical treatment of acneinclude isotretinoin, retinoyl _-glucuronide andmotretinide. However, according to Zaenglein ,these topical retinoid formulations areunavailable in the USA, although they arecommonly used in the European Union. Of thesethree retinoids, only isotretinoin is available as atopical formulation in South Africa.

AntibioticsTopical antibiotics are generally used for mild tomoderate inflammatory acne. They have activityagainst P. acnes, and therefore act on thesurface of the skin to reduce the stimulus forinflammation of the lesions . Due to certain sideeffects and lesser effectiveness of topicalchloramphenicol and tetracyclines, these drugsare less frequently used.The most popular topicalantibiotics used in acne treatment are




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erythromycin and clindamycin, but, in recentyears, the continuous use of these antibiotics hasled to the increasing development of resistanceagainst P. acnes strains. Therefore, it isrecommended that mono therapy with topicalantibiotics are used for only a short time period(12 weeks) and that the antibiotics should becombined with benzoyl peroxide, zinc or retinoidsto prevent bacterial resistance . The use of oraland topical antibiotics in combination to treatacne should be avoided.

ErythromycinErythromycin is a macrolide antibiotic thatattaches to the 50S ribosomal unit of bacteriumand prevents translocation, which is necessaryfor protein synthesis of the bacteria . It is activeagainst P. acnes and reduces the colony on thesurface of the skin and within follicles. It hasbeen regarded as a very effective topicalantibiotic in acne therapy, but recently it wasdiscovered that erythromycin is up to 60%resistant to P. acnes which makes it lessdesirable. This has led to interest in the futuredevelopment of other topical antibiotics.

ClindamycinClindamycin is classified as a lincosamideantibiotic. It is a semi-synthetic derivative of theantimicrobial agent, lincomycin. Clindamycinattaches to the 50S ribosomal subunit andinhibits protein synthesis of the bacteria and as

with erythromycin; it also inhibits P. acnes on thesurface of the skin .Diverse TreatmentsOther topical treatments used for acne, such asfor example chemical peels, benzoyl peroxide,dapsone, etc. will be discussed in the followingsection.Salicylic AcidSalicylic acid is known as a keratolytic agentwhose mechanisms of action is to dissolve theintercellular cement which holds the cells of theepithelium together. It has a minor antiinflammatory effect, enhances penetration ofcertain substances and at low concentrations it isfungistatic and bacteriostatic. Salicylic acid isfound in a number of over-the-counter productsfor acne treatment.

Chemical Peeling with Hydroxy AcidsChemical peels involve facial resurfacingwhereby removal of the epidermis stimulates re-epithelization and skin rejuvenation . Chemicalpeeling also appears to reducehyperpigmentation and superficial scarring of theskin. This therapy can be divided into differentgroups according to its penetration depth anddestruction. Alpha-hydroxy acids (i.e., glycolicacid and lactic acid) and beta-hydroxy acids (i.e.,salicylic acid) are the most common chemicalsused in chemical peels. A much higherconcentration of salicylic acid (20%–30%) is




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present in chemical peels than found in dailyacne cleansers. There exist little evidence/datathat peels are relatively safe to use. Therefore, itshould be regarded as a complementarytreatment rather than a first-line treatment.

Benzoyl PeroxideBenzoyl peroxide is a topical disinfectant,originally employed as a peeling agent fortreating acne. It possesses diverse properties,making it both a comedolytic and an antibacterialagent, with no effect on sebum production.Benzoyl peroxide has proven bactericidal activityagainst P. Acnes by releasing free radicaloxygen, which degrades the bacterial proteins.Bershad stated that in addition to its successfultreatment of inflammatory acne, benzoyl peroxideAlso decreases the Insoluble benzoyl

Soluble benzoyl peroxide (Novel drug) .

Benzoyl peroxide cream

number of comedones on the skin. Benzoylperoxide is an important treatment for mild tomoderate acne and, although it can be used asmonotherapy for a period of 6–8 weeks, is oftencombined with topical antibiotics in order toreduce the resistance of the P. acnes speciesand to increase the efficacy of treatment .Gollnick and Krautheim suggested that benzoylperoxide is best combined with topical retinoids.However, it has been found that all retinoids(except for adapalene) are unstable whencombined with benzoyl peroxide and shouldtherefore be applied separately . The main sideeffects of benzoyl peroxide include burning,dryness, erythema, peeling or stinging .

Azelaic AcidAzelaic acid is a natural dicarboxylic acid thatinhibits protein synthesis of the P. acnesspecies. It is an effective agent because it hasbacteriostatic, anti-inflammatory, antioxidant andanti-keratinizing properties. Thusfar, no bacterialresistance of P. acnes exists with azelaic acid. Ithas also been suggested that when azelaic acidis used in conjunction with clindamycin, benzoylperoxide or _-hydroxy acids it will be moreeffective. Sulfur In the past, sulfur was frequentlyused in preparations for acne. This active has,however, become unpopular due to its bad odor.Sulfur is a chemical that has demonstrated tohave mild keratolytic and bacteriostatic




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properties. Sulfur is reduced to hydrogen sulfideinside the keratinocytes which is said to breakdown keratin in the skin. According to Akhavanand Bershad, sulfur also has activity against P.acnes.

NiacinamideNiacinamide is an active amide of vitamin B3 andis composed of niacin (also known as nicotinicacid) and its amide. It may also be referred to asnicotinamide .Its mechanism of action can beexplained as the inhibition of sebocytesecretions, resulting in less sebum productionwhich reduces the oiliness of the skin. It also hasanti-inflammatory properties which have provedto be beneficial in pustular as well as papularacne. Topical application of a 4% niacinamidehas led to significant improvements to acne allover the world .

Topical CorticosteroidsTopical corticosteroids can be used in certainconditions, as for example to treat veryinflammatory acne. The treatment period should,however, be short and proof of their efficiencyshould still be determined.

TriclosanTriclosan is an antibacterial agent (antiseptic)which can be used to treat acne . It wasdetermined that bacterial populations did notdevelop resistance to triclosan under clinical

conditions . No adverse effects are anticipatedwhen triclosan containing products are used asrecommended.

Sodium SulfacetamideThis agent belongs to the sulfonamideantibacterial group. It is bacteriostatic byinhibiting deoxyribonucleic acid (DNA)-synthesisthrough competitive antagonism of para-aminobenzoic acid (PABA). Sodiumsulfacetamide has activity against a number ofgram-positive and gram-negative agents, but isgenerally only used when other topical agentscannot be tolerated by patients .

DapsoneDapsone possesses antibacterial and anti-inflammatory activity, although its precisemechanism of action against acne is stillunknown. However, it has recently beensuggested that dapsone’s mechanism of action inthe treatment of acne may be due toantimicrobial and anti-inflammatory effects.Dapsone gel (5%) can be used to reduceinflammatory as well as non-inflammatory acnelesions. This agent’s lower cost makes it morefavorable for use in developing countries;however, it is not recommended as first-linetherapy.

Systemic TreatmentOral systemic treatment is required when acne is




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resistant to topical treatment or if it manifests asnodular lesions or leaves scarring. It is thepreferred choice in the treatment of inflammatorylesions. Systemic treatment may also be requiredto prevent social embarrassment andpsychological impairment in people sufferingfrom acne. The most common systemictreatment includes isotretinoin, oral antibioticsand hormonal agents .

RetinoidsIsotretinoin is a systemic retinoid and derivativeof vitamin A. It is currently being used as a firstline treatment for severe nodular or inflammatoryacne and is the only known medication which hasthe potential for the suppression of acne in thelong term. It can also benefit patients with mild tomoderate cases of acne that have provedresistant to topical or other oral agents in thepast. It is also considered as a first line treatmentin severe acne of the face and trunk, acne thatcauses scarring and acne that causespsychological complications .Currently, isotretinoin is the only drug availablewhich has an effect on all four pathogenic factorsof acne . Isotretinoin causes de-differentiation ofthe sebaceous gland, decreasing the sebumproduction which will lead to a change in theecosystem of the cutaneous bacterial flora,ultimately reducing P. acnes colonization in thefollicles. It also causes the shedding of the

keratinocytes. Isotretinoin treatment is normallyover a course of 16–24 weeks. It is necessary toclosely monitor patients who use isotretinoinbecause of its harmful side-effects .

AntibioticsOral antibiotics are generally indicated formoderate to severe inflammatory acne, acne thatshows resistance to previous topical treatment orfor acne that covers a large surface area of thebody. Acne is often treated with oral antibioticssuch as macrolides (erythromycin, clindamycin,azithromycin and roxithromycin),fluoroquinolones (levofloxacin), tetracyclines(doxycycline, minocycline and lymecycline) andco-trimoxazole . These antimicrobial agentsinhibit the growth of P. acnes and the synthesisof inflammatory mediators released from P.acnes. The success of the antibiotic treatment isbased on the ability of the agent to reach the lipidenvironment of the pilosebaceous follicles in thedermis, which is the area where P. acnescolonize. Tetracyclines are very popular becausethey are effective and inexpensive. Doxycyclineand minocycline are preferred because theycause less gastrointestinal irritation, and they aremore lipid soluble, penetrating the pilosebaceousfollicle more efficiently. The tetracycline familyexhibits both anti-inflammatory as well asantibacterial properties. Additionally, lessresistance in P. acnes have been reported with




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the tetracyclines than the macrolides . Not manystudies have been performed to determine theefficacy of azithromycin in the treatment of acne,whereas clindamycin (topical) and erythromycin(topical and oral) have been well recognized asacne treatments. Erythromycin and clindamycinhave little anti-inflammatory activity and mainlywork by reducing the levels of P. acnes. Sincethese antibiotics are used repetitively at lowdoses for extended periods of time during acnetreatment, increasing resistance has developedovertime which has resulted in limited use ofthese agents. To reduce resistance and improvethe efficacy, oral antibiotics should be combinedwith topical benzoyl peroxide or retinoids.Additionally, the duration of treatment should notexceed 12 weeks when feasible. It has also beensuggested that if a patient is a good candidate fortreatment with isotretinoin, long-term antibiotictreatment is unfeasible .

HormonalSebaceous glands are androgen dependent andtherefore the effect of androgen on sebaceousglands can be treated with hormone therapy.Hormonal treatment can be used as analternative for adolescent and adult females.These hormones are most commonly given in theform of oral contraceptive pills. The contraceptivehormones reduce the sebum production that isinitially induced by androgen. It increases the

synthesis of sex hormone-binding globulin whichin turn decreases biologically active freetestosterone in the female body. Although allcontraceptives can be used to treat hormonerelated acne, progestins are usually preferredbecause they possess no androgen activity . Oralcontraceptives can be used alone or incombination with other therapies to treat acne inWomen. The treatment period of acne withhormonal anti-androgens must be at least for 12months and oftentimes even longer as thefavorable effect of hormonal agents will only bevisible after 3–6 months of treatment.Spironolactone is an alternative drug which canalso be combined with oral contraceptives in thetreatment of hormone related acne. Itsmechanism is based on the fact that it is anandrogen receptor blocker. It is especiallyeffective for patients with inflammatory acne .

Diverse TreatmentsOther oral treatments that can possibly be usedas adjunctive acne therapy include zinc sulfate,ibuprofen (due to its anti-inflammatory effect) andclofazimine. Systemic corticosteroids can beused for initial treatment of inflammatorymanifestations (Acne fulminans). It can also beused to manage aggravation of acne whentreating with systemic isotretinoin . It has beenrecommended that severe inflammatory Acnevulgaris, Acne fulminans and Pyoderma facials




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be treated with oral prednisone (0.5–1.0 mg/kgdaily) for a period of 4–6 weeks, after which thedosage can be decreased graduall.

Complementary and Alternative Medicines(CAM)More efficient and safer treatment options areneeded for the treatment of acne . NumerousCAM therapies have been noted and/orpromoted for use as acne treatment and aregenerally regarded as safe. Botanical therapieshave the added benefit of possessing severalmodes of action due their composition consistingout of a range of possible active components. Ithas been proposed that CAM therapies influencethe androgenicity, increased sebum activity,infection, inflammation and hyperkeratinizationassociated with acne. However, in most casesevidence for their use is inadequate and oneshould still be wary of the possible harm and sideeffects these plant-derived products can lead to.Some researchers are of the opinion thatbotanicals may lessen resistance when used asalternatives to or in combination with antibiotics.This should, however, still be verified with clinicalstudies. Various articles list all the possibleplant/herbal remedies for acne. Some of theseingredients do however have some anti-inflammatory, moisturizing and soothingproperties. Therefore, theoretically, theseingredients should be able to help relieve some

of the drying effects caused by the more vigorousacne therapies and the erythema associated withinflammatory acne. The absence of clinical dataon the efficacy of these complimentary remediesis of big concern and need to be addressed byfuture research. For the purpose of this article,only a few of the major CAM therapies will bediscussed in detail. There is, however, a strongpossibility that the range of CAM therapies beingused by acne patients is much larger than theseries of treatments mentioned in this review.Basil OilAdvocated topically applied basil essential oils forthe treatment of acne include Ocimum sanctum,Ocimum basilicum and Ocimum gratissimum .Since ancient time, Thai basil oils such as O.basilicum L. (sweet basil) and O. sanctum L.(holy basil) have been used as traditionalmedicine to treat ringworm and insect bites .Studies showed that topical application of apreparation containing O. gratissimum oil in acetomacrogol blend base were more efficient andreduced lesion counts faster than a 10% benzoylperoxide lotion . A study on Thai basil oilsshowed that O. basilicum and O. sanctumshowed promise to be used for acne treatmentas they exhibited antimicrobial activity against P.acnes. The formulations containing O. basilicumshowed a higher anti-P. acnes activity than theO. Sanctum containing formulation .




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Copaiba OilCopaiba oil-resin has traditionally been used asan antiseptic, anti-inflammatory and healingagent. Da Silva et al. conducted a double-blindplacebo controlled clinical trial in which thecopaiba oil was prepared into a topical gel todetermine its activity against Acne vulgaris. After21 days of treatment, the copaiba oil gel stoppedthe outbreak of new pustules, healed pre-existentpustules and reduced the area of erythema. Theauthors concluded that copaiba oil may be usedin the treatment of mild acne, although largerstudies are necessary to confirm.

Green TeaGreen tea possesses anti-inflammatory, anti-oxidant, antimicrobial and antimutagenicproperties which can be ascribed to its highcontent of polyphenols, including catechins(flavan-3-ols). The main catechins found in greentea include epigallocatechin-3-gallate (EGCG),epigallocatechin (EGC), epicatechin-3-gallate(ECG) and epicatechin (EC) of which EGCG isthe most abundant polyphenol found in green teaPolyphenon-60 from green tea is a mixture ofpolyphenolic compounds . Topical application ofpolyphenon-60 in patients with mild-to-moderateacne (in vivo testing) decreased the averageamount of open-comedos and pustules.However, polyphenon-60 showed noimprovement on closed-comedos. In vitro studies

to determine the underlying mechanism by whichpolyphenon-60 has this therapeutic effect onacne showed that this compound suppresses theinflammation process . Yoon et al. conducted invitro studies in which it was determined thatEGCG directly targets three pathologicalprocesses of acne as it has sebo-suppressiveeffects, it inhibits the growth of P. acnes and ithas anti-inflammatory effects. They also foundthat EGCG may reverse the modifiedkeratinization of follicular keratinocytesassociated with acne. These results werefollowed by a double-blinded, split-face clinicaltrial which showed that the mean inflammatoryand non-inflammatory lesion counts significantlydecreased after eight weeks of treatment with anEGCG solution when compared to the baselinevalues. Results obtained from a double-blind,placebo-controlled, randomized clinical trialshowed that when green tea extract was givenorally it was found to be effective against acnelesions in mild-to-moderate acne cases.Compared to the control, the green tea extractsignificantly decreased the inflamed and totallesion counts, although no significant effect wasobserved on the non-inflamed lesion count. Atopical 3% green tea emulsion was found todecrease the sebum production of the cheeks ofhealthy male volunteers over a 60 day period.Minerals




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Minerals have been used for healing purposessince prehistoric times. The minerals being usedfor therapeutic intents are mostly clay mineralssuch as kaolinite, palygorskite, smectites andtalc. Clay minerals can be used to treat acne,blackheads and spots. Generally it is applied asa face mask consisting of a warm mixture ofwater and clay which will open pilosebaceousorifices, stimulate perspiration and sebaceoussecretions. A mix of minerals (consisting primarilyof halloysite, sericite and talc) obtained from oresindigenous to Korea showed to inhibit the growthof S. Epidermidis and P. acnes . Dead Sea blackmud showed marked antimicrobial action whentest microorganisms (P. acnes) were added tothe mud where after they lost their viability.Additionally, when Dead Sea mud was placed onP. acnes inoculated agar plates, a growthinhibition zone was observed . Another mineralcommonly used both systemically as well astopically for the treatment of Acne vulgarisincludes zinc which was mentioned earlier.

Antimicrobial PeptidesNatural antimicrobial peptides representpromising therapies for treating acne as they areunlikely to provoke drug resistance inmicroorganisms . However, some authors havestated that development of peptide-based drugresistance has been proven experimentally,although, when compared to conventional

antibiotics it is considered to arise at a muchslower pace .A synthetic peptide, derived from epinecidin-1(from the marine organism Epinepheluscoioides), have shown bactericidal propertiesagainst P. acnes by means of destroying itsmembrane . In another study, antimicrobialpeptides derived from ranid frog skins showed ahigh potency against P. acnes . Wang and co-workers purified a snake cathelicidin-derivedantimicrobial peptide, cathelicidin-BF, from thevenoms of Bungarus fasciatus. When tested invitro it was observed that cathelicidin-BFpossessed potential antimicrobial activity againstP. acnes, comparable to that of the antibiotic,clindamycin. Additionally, this antimicrobialpeptide showed some anti-inflammatory effectsand inhibited P. acnes-induced O2 production. Allthese properties suggested the potential use ofcathelicidin-BF for treating Acne vulgaris.

ResveratrolConsidering the pathophysiology of acne, theideal drug should be capable of reducing theinflammatory response as well as inhibiting P.acnes . As a result resveratrol is emerging as anew approach in treating acne as it possessesanti-proliferative, anti-inflammatory and P. Acneinhibiting properties . Resveratrol is a naturalphytoalexin which is produced by certainspermatophytes, such as for example grapes. A




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single-blind, vehicle-controlled pilot study wasperformed in which resveratrol (trans-isomer)was formulated into a gel with acarboxymethylcellulose base. This formulationwas applied on the right side of the face ofvolunteers with inflammatory Acne vulgaris in thefacial area for 60 days and compared to the leftside of the face on which the control (hydrogelvehicle) was applied. All the volunteers had anoteworthy reduction in pustular lesions andinflammation with an overall noticeable clinicalimprovement on the side of the face treated withresveratrol. The resveratrol-treated side of theface also showed a significant decrease ofmacrocomedones and microcomedones whencompared to the vehicle-treated side of the face.It seemed as though resveratrol inhibited thekeratinocyte hyperproliferation process.Resveratrol was found to inhibit P. acnes growthwhen tested in vitro. It was bacteriostatic at lowerconcentrations (50 mg/L and 100 mg/L) andbactericidal at the highest concentration tested(200 mg/L). The inhibiting effect of resveratrolcompared well with the activity of frequently usedacne treatments benzoyl peroxide anderythromycin.

Novel drug delivery system and its use intreatment ACNE:The method by which a drug is delivered canhave a significant effect on its efficacy. Some

drugs have an optimum concentration rangewithin which maximum benefit is derived, andconcentrations above or below this range can betoxic or produce no therapeutic benefit at all. Onthe other hand, the very slow progress in theefficacy of the treatment of severe diseases, hassuggested a growing need for a multidisciplinaryapproach to the delivery of therapeutics totargets in tissues. To minimize drug degradationand loss, to prevent harmful side-effects and toincrease drug bioavailability and the fraction ofthe drug accumulated in the required zone,various drug delivery and drug targeting systemsare currently under development. Novel drugdelivery strategies can play a pivotal role inimproving the topical delivery of antiacne agentsby enhancing their dermal localization with aconcomitant reduction in their side effects.This novel formulation helps by encouragingcollagen production in the skin. It helps improveoverall skin tone and luster and improves theappearance of fine lines. It is made of acombination of collagen and Hyaluronic acid.Light, oil-free lotion contains finely milledprescription-grade medicinal agents to healblackheads and blemishes and helps preventfuture breakouts. The advanced delivery systemin Repairing Lotion is soothing and safe for entireface.Novel Topical Delivery Systems:




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Targeting is the ability to direct the drug-loadedsystem to the site of interest. Controlled drugrelease and subsequent biodegradation areimportant for developing successful formulations.Potential release mechanisms involve:(i) Desorption of surface-bound /adsorbed drugs;(ii) Diffusion through the carrier matrix;(iii) Diffusion (in the case of nanocapsules)through the carrier wall;(iv) Carrier matrix erosion; and(v) A combined erosion /diffusion process.1. Aerosol Foams:Aerosol foams have become an increasinglypopular type of topical formulation for a variety ofskin conditions including acne vulgaris. Thevehicle base of the foam can have a liquid orsemi-solid consistency that shares the samephysicochemical characteristics of conventionalvehicles like creams, lotions and gels, but itmaintains desirable properties such asmoisturizing/ fast-drying effects, or higher drugbioavailability. The aerosol base is dispensedthrough a gas-pressurized can that dischargesthe foam. The product characteristics (i.e.,texture, bubble size and thickness, viscosity,density, persistence, stability, and spreadability)are determined by the type of formulation and thedispensing container that are selected to suit thespecific treatment needs. In acne, foams may bepreferred for application on large hairy surfaces(e.g., chest and back) or on the face ascleansers, because they are easier to apply.

2. Liposomes:Liposomes are frequently used as vehicles inpharmaceuticals and cosmetics for a controlledand optimized delivery to particular skin layers.Liposomes are spherical vesicles whosemembrane consists of amphiphilic lipids (i.e.,lipids that are hydrophilic on one side andlipophilic on the other side) that enclose anaqueous core, similar to the bilayer membranesof living cells. Because liposomes offer anamphiphilic environment, they may encapsulatehydrophilic substances in their aqueous core andlipophilic substances in their lipid bilayer. Thisunique dual release capability enables thedelivery of two types of substances once they areapplied on the skin; each differs in its effects onskin permeability, which may enhance thedesired therapeutic benefit.

3. Nanoemulsions:Nanoemulsions are a class of emulsions (i.e.,water-in-oil or oil-in-water formulations) that arecharacterized by the dispersion of very small-sized droplets when mixed. Nanoemulsions arenot formed spontaneously, as they requireunique thermodynamic conditions, specializedmanufacturing processes, and specificsurfactants that can stabilize the nano droplets.Nanoemulsions are suitable for the transport oflipophilic compounds into the skin and, therefore,they may be an ideal vehicle for use in acne to




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increase the penetration of the active compoundsinside the lipophilic environment of thepilosebaceous unit. In addition, nanoemulsionparticulates will not clog the pores and they canproduce additional therapeutic effects, such asincreased skin hydration and viscoelasticity.

4. Polymers:Polymers are large molecules consisting ofrepeating structural units, or monomers that areconnected by covalent chemical bonds. Thesecompounds serve as the building blocks ofnatural (e.g., paper and amber), biological (e.g.,proteins and nucleic acid), or synthetic (e.g.,plastics and polyethylene) materials. Today,applications for synthetic polymers can be foundin nearly every industry, and their versatility hasgiven rise to technological advancements withinthe pharmaceutical sector that address a varietyof medical needs. For example, in dermatology,there are new acrylic-acid polymers that turn intoa gel in the presence of water by trapping waterinto microcells. Inside these aqueous microcells,hydrophilic compounds can remain in a solution,where as non-hydrophilic compounds may bedispersed in suspension. The result is a stablegel-like formulation that is easy to use andreleases the active compounds once they areapplied on the skin. Moreover, thesepolymerbased gels can be mixed with otherexcipients, such as moisturizers and emollients,

to provide additional clinical benefits. Recentlyintroduced anti-acne formulations that combineclindamycin 1% with benzoyl peroxide 5% utilizethis novel polymer-based gel technology thatexhibits efficacy and excellent tolerability.

5. Microsponges:Microsponges are biologically inert particles thatare made of synthetic polymers with the capacityto store a volume of an active agent up to theirown weight. Furthermore, the particles serve toprotect the entrapped active compound fromphysical and environmental degradation. Themicrosponge technology can be utilized in avariety of formulations, but is more frequentlymanufactured as gels. Once applied on the skin,microsponges slowly release the active agents.

6. Emulsifier Free Formulations:Emulsifier-free formulations are also a growingarea of development for dermatologic andcosmetic products. Most skin care products areemulsions, i.e., a mixture of two or morematerials that are not miscible with each other;as such, according to the second law ofthermodynamics, they are inherently unstable. Asa result, they require the addition of surfactants(emulsifiers) that stabilize the formulation toguarantee an adequate shelf life. Furthermore,once these surfactant agents are applied on theskin, they tend to emulsify and remove thenatural lipids of the epidermis. Consequently, the




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pharmaceutical industry has been developingsurfactant-free emulsions as alternatives toconventional formulations by using stabilizers,such as polymeric emulsifiers or solid particles, inorder to yield sufficiently stable products with acosmetically pleasant appearance.

7. Fullerenes:Fullerenes are molecules composed entirely ofcarbon that resemble a hollow sphere. Oncefullerenes come into contact with the skin, theymigrate through the skin intercellularly, asopposed to moving through cells. Therefore, afullerene could be used to 'trap' activecompounds and then release them into theepidermis once they are applied on the skin.Moreover, fullerenes, themselves, are thought tobe potentially potent antioxidants. Data arereported in the literature showing that fullerenesare well tolerated and they hold substantialpromise in dermatologic and cosmeticapplications.

ConclusionThe increasing importance of appearance andthe influence of disfiguring on psychologic healthconfirm the significance of the disease ‘‘acne’’.Although during the past 50 years dramaticprogress has been made concerning thedevelopment of treatment modalities, thepathomechanism is still not fully understood.Molecular biology combined with molecular

immunology and pharmaceutical research isnecessary to clarify these issues.

AcknowledgementI am heartily thankful to Prof Dr. Pardeep KumarGoyal (Department of Pharmachemistry) a B.N.Institute of Pharmaceutical Sciences, whoseencouragement, guidance and support from theinitial to the final level enabled me to develop anunderstanding of the subject to complete thisreview article. Lastly, I offer my regards to all ofthose who supported me in every respect duringthe completion of the project.

REFERENCE

1. Patel Rakesh P, “Novel Anti-Acne DrugDelivery System of Tretinoin” Intl. R. J. ofPharmaceuticals (2011), 1(2), ISSN 2048-4143:65-71.2. Jotish M, “Novel Drug Delivery System andits use in the treatment of acne” Int. Journal OfPharmacy & Technology IJPT March 2010,

2(1) ISSN: 0975-766X: 41-53.

3. Haider, A, Shaw, JC. Treatment of acnevulgaris. JAMA 2004; 292:726.4. A.A. Date, B. Naik, M.S. Nagarsenker, Noveldrug delivery systems: Potential in improvingDelivery of Antiacne agents, J. of Pharmacologyand Biophysical research 2006:19(1): 2-165. Bershad, S.V. The modern age of acnetherapy: A review of current treatment options.




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Mt Sinai J. Med. 2001, 68: 279–85.6. Dessinioti, C.; Katsambas, A.D. The role ofPropionibacterium acnes in acne pathogenesis:Facts and controversies. Clin. Dermatol. 2010,28: 2–7.7. Krautheim, A.; Gollnick, H.P.M. Acne: Topicaltreatment. Clin. Dermatol. 2004, 22: 398–407.8. Thibout, D.; Gollnick, H.; Bettoli, V.; Dréno,B.; Kang, S.; Leyden, J.J.; Shalita, A.R.;Lozada, V.T.; Berson, D.;Finlay, A.; et al. Newinsights into the management of acne: Anupdate from the global alliance to improveoutcomes in acne group. J. Am. Acad.

Dermatol. 2009, 60: S1–S50.9. Lavers, I. Diagnosis and management ofAcne vulgaris. Nurse Prescr. 2014, 12: 330–36.10. Adebamowo, C.A.; Spiegelman, D.; Berkey,C.S.; Danby, F.W.; Rockett, H.H.; Colditz, G.A.;Willett, W.C.;Holmes, M.D. Milk consumptionand acne in teenage boys. J. Am. Acad.Dermatol. 2008, 58: 787–93.11. Gollnick, H. Current concepts of thepathogenesis of acne, Implications for DrugTreatment. Drugs 2003, 63:1579–1596.12. Akhavan, A.; Bershad, S. Topical acnedrugs. Am. J. Clin. Dermatol. 2003, 4: 473–492.

Source of Support: Nil, Conflict of Interest:None


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