NANOTECHNOLOGY IN TUBERCULOSIS
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Transcript of NANOTECHNOLOGY IN TUBERCULOSIS
Potential of Nanotechnology as a delivery platform against
Tuberculosis
Guided by:Dr. K.N. Gujar M.Pharm, Ph.D
Co-guided by: DR. M.S. GAMBHIRE
M. Pharm, Ph.D
Presented by:Mr. Aniket A. Vaidya
M. Pharm 1st sem.Pharmaceutics
Roll no. 522
Sinhgad College Of Pharmacy, Vadgaon (BK), Pune-41
A seminar on
Date of seminar: 29 OCT. 2015
1 Aniket A. Vaidya
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Introduction:Tuberculosis is an airborne disease caused by the bacterium Mycobacterium tuberculosis (M. tuberculosis) .mycobacterial species : (M. bovis, M. africanum, M. microti, M. caprae, M. pinnipedii, M. canetti and M. mungi) together comprise what is known as the M. tuberculosis complex. M. tuberculosis organisms are also called tubercle bacilli.
Jung Kwon Oha et al , The development of microgels/nanogels for drug delivery applications, Progress In Polymer Science 33 (2008) 448–477
Mycobacterium tuberculosis
Types of Tuberculosis
Ganga Srinivas et al.” Polymer Based Microgels/Nanogels: Development and Application In Drug Delivery” Am. J. PharmTech Res. 2014; 4(1) ISSN: 2249-3387
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Symptoms and Sings of Tuberculosis
Ganga Srinivas et al.” Polymer Based Microgels/Nanogels: Development and Application In Drug Delivery” American Journal of Pharma Tech .Research. 2014; 4(1) ISSN: 2249-3387
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Pathogenesis of TB
Jung Kwon Oha et al , The development of microgels/nanogels for drug delivery applications, Prog. Polym. Sci. 33 (2008) 448–477
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NANOTECHNOLOGY
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Nanotechnology is the study of extremely small structures, having size of 0.1 to 100 nm
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Routes and mechanisms of particle transport across epithelia
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Nanoparticle transport
Jung Kwon Oha, Ray Drumright et al , “The development of microgels/nanogels for drug delivery applications”, Progress in Polymer Science. 33 (2008) 448–477.
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Objective
Jung Kwon Oha, Ray Drumright et al , “The development of microgels/nanogels for drug delivery applications”, Progress in Polymer Science. 33 (2008) 448–477.
Fig:Reverse micellar method for the preparation of nanogels.
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Jung Kwon Oha, Ray Drumright et al , “The development of microgels/nanogels for drug delivery applications”, Progress in Polymer Science. 33 (2008) 448–477.
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Encapsulation of ATDs into multifunctional polymeric nanoparticles.
Encapsulation of all four drugs
Sanjida Sharmin et al, “ An Overview of Nanogel Drug Delivery System”. Journal of Applied pharmaceutical science vol.3 september 2013.
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PLGA Nanocapsule
Encapsulation of pre-formed drug-loaded micelle-like containers
Pharmaceutical consideration
1. Drug loading:
a. Post formation loadingb . In situ loading
2. Covalent conjugation3. Self assembly
Ganga Srinivas et al.” Polymer Based Microgels/Nanogels: Development and Application In Drug Delivery” American Journal of Pharma Tech .Research. 2014; 4(1) ISSN: 2249-3387
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PROPERTIES
• Biocompatibility and degradability
• Swelling property
• Higher drug loading capacity
• Particle size
• Solubility
• Electromobility
• Colloidal stability
• Others
Sanjida Sharmin et al, “ An Overview of Nanogel Drug Delivery System”. Journal of Applied pharmaceutical science vol.3 september 2013.
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CASE STUDY : 1
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MaterialsChitosanPolylacticacidDichloromethanePolyethylene
glycolGelatinPoly(ethylene
oxide)Phosphate buffer
salineRifampicin
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Methods
Preparation of CS-PLA nanoparticles
Preparation of Rifampicin loaded CS-PLA nanoparticles
Method of preparation
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Aq. Solution of drug + polymer solution
w/o emulsion poured into 10ml of 1% acetic acid solution contain 60mg of CS & 200mg of PEO
Add water , nanoparticles ppt then cooled at 10oC
Mixture sonicate for 60 min Form emulsion
Nanoparticles evaoporated by rotary evaporator
Then the above mentioned procedure was followed and added PEG and gelatin.
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The prepared nanoparticles were named as
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chitosan–polylactic acid encapsulated rifampicin (CS–PLA–RIF),
chitosan–polylactic acid–polyethyleneglycol encapsulated rifampicin (CS–PLA–RIF–PEG)
and chitosan–polylactic acid–polyethylene glycol–gelatin encapsulated rifampicin (CS–PLA–RIF–PEG–G).
Results :
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Fig.The zeta pontential values of CS–PLA–RIF, CS–PLA–RIF–PEG,CS–PLA–RIF–PEG–G with various concentrations.
Particle size and zeta potential of the prepared nanoparticles
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Surface morphology
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Fig. 2. SEM images of rifampicin (a), CS–PLA–RIF (b), CS–PLA–RIF–PEG (c) and CS–PLA–RIF–PEG–G (d).
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FTIR Spectra
Fig. 3. FTIR spectra of CS–PLA–RIF, CS–PLA–RIF–PEG and CS–PLA–RIF–PEG–G (a),and 10–50% of RIF encapsulated CS–PLA–RIF–PEG–G (b).
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In vitro studies
Fig. 4. In vitro analysis of rifampicin prepared nanoparticles.
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Cell inhibition studies
The relative cell viability of RIF, CS–PLA–RIF, CS–PLA–RIF–PEG and CS–PLA–RIF–PEG–G nanoparticles
Conclusions:In this study, the effectiveness of SLN gel for dermal
delivery of MLX was investigated.They seemed appropriate for sustained and controlled
release due to the possible formation of a drug depot in the skin. Thus,
It can be concluded that SLNs offer a better option for the delivery of NSAIDs via skin in order to avoid gastrointestinal side effects which occur after oral administration.
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CASE STUDY : 2
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Materials Poly(lactic-co-glycolic acid) (PLGA)(lactic acid:glycolic acid ratio=75:25) Nanoparticles-containing mannitol (MAN) Rifampicin (RFP) Rat normal alveolar macrophage cells Coumarin 6 Indomycin green (ICG)
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Methods Preparation of RFP-PLGA nanoparticle-containing MAN
microshperes using a four-fluid nozzle spray drier
Preparation of RFP-PLGA microspheres using a
traditional two-fluid spray drier
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Preparation of RFP–PLGA nanoparticles-containing MAN microspheres using a four-fluid nozzle spray drier (model MDL-050)
RFP:PLGA (1:10)
dissolved at 1.67%(w/v) in a 2:1 solution of acetone/methanol
MAN
dissolvedIn water at 16.7% (w/v)
RFP–PLGA:MAN composition ratioof 1:10 (w/w)
29The RFP/MAN micro particles were prepared in the same manner
Spray drying conditions:inlet temperature, 60 °C; supply rate for coumarin–PLGA or MANsolutions, 5 mL/min; spray rate for air, 30 L/min; spray air pressure,0.78 MPa.
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Schematic diagram of the four-fluid nozzle
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Preparation of RFP–PLGA microspheres using a traditional two-fluidspray drier (Pulvis mini-spray GB22)
RFP:PLGA ratio
was 1:10RFP and PLGA were dissolved at 4.4%(w/v) in a 2:1 solution of acetone/methanol
Water was added at 5%v/v in the spray solution
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Spray drying conditions: inlet temperature, 50 °C; supply rate for solution,5mL/min; spray air pressure, 0.29 MPa
Result
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Fig. 1 SEM photographs and images of the RFP/PLGA microspheres, the (RFP/PLGA)/MAN microspheres, and the RFP/PLGA nanoparticles dispersed in MAN.
In-vitro studies
Fig. 2. In vitro uptake percentage of coumarin by alveolar macrophage cells afteradministration of the coumarin/PLGA microspheres and the (coumarin/PLGA)/MANmicrospheres. Dose: 1 μg of coumarin/well. Each point represents the mean±S.D. (n=3).
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Fig. 3. Aerosol performances of RFP/PLGA microspheres and (RFP/PLGA)/MAN microspheres.Each point represents the mean±S.D. (n=3). □, RFP/PLGA microspheres;■, (RFP/PLGA)/MAN microspheres
In-vivo drug release studies
Fig. 5. In vivo uptake of RFP by alveolar macrophages in lungs of rats after administrationof RFP/MAN, RFP/PLGA,and(RFP/PLGA)/MAN microspheres. Dose: 150 μg/kg of RFP.Each point represents the mean±S.E. (n=6).
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Fig 6 In vivo fluorescent images of lungs of rats after administration of ICG/PLGA and (ICG/PLGA)/MAN microspheres
Conclusion
pH responsive chitin-PCL CNGs were developed and a hydrophilic drug,
Dox. was effectively loaded on to the Chitin-PCLCNGs
DTA confirmed the thermal stability of Dox-Chitin-PCL CNGs. swelling
and drug release at acidic pH.
In addition the Dox-Chitin-PCL CNGs shows significant cytotoxic effects
against A549 (lung cancer) cells. These studies prove the potential of
Chitin-PCL CNGs as a promising drug delivery vehicle for lung cancer.
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Conclusion:
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Nanogels are promising and innovative drug delivery system . Nanogels appear to be excellent candidates for brain
delivery .This will be especially important for the targeting of cancer cells.
REFERENCES
1. Jung Kwon Oha, Ray Drumright et al , “The development of microgels/nanogels for drug delivery applications”, Progress in Polymer Science. 33 (2008) 448–477.
2. Sanjida Sharmin et al, “ An Overview of Nanogel Drug Delivery System”. Journal of Applied pharmaceutical science vol.3 september 2013.
3. L.Divya1, V. Ravichandiran et al , “Nanogels – as A Drug Delivery Carrier” , Indo American journal of pharmaceutical research.
4. Reuben T. Chacko, Judy Ventura et al, “Polymer nanogels: A versatile nanoscopic drug delivery platform” , Advanced Drug Delivery Reviews 64 (2012) 836–851.
5. Reuben T. Chacko, Judy Ventura, Jiaming Zhuang, S. Thayumanavan , “Polymer nanogels: A versatile nanoscopic drug delivery platform”, Advanced Drug Delivery Reviews 64 (2012) 836–851.
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6. Dhawal dorwal , “Nanogels as novel versatile pharmaceuticals” , International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 4, Issue 3, 2012
7. Ganga Srinivas, Pooja Ramnathkar, “Polymer Based Microgels/Nanogels: Development and Application In Drug Delivery”, Am. J. PharmTech Res. 2014; 4(1) ISSN: 2249-3387.
8. Farhana Sultana S. Khuranaa, P.M.S. Bedia, N.K. Jainb, “Preparation and evaluation of solid lipid nanoparticles based nanogel for dermal delivery of meloxicam”, Chemistry and Physics of Lipids (2013).
9. T.R. Arunraj, N. Sanoj Rejinold, N. Ashwin Kumar, R. Jayakumar, “ Doxorubicin-chitin-poly (caprolactone) composite nanogel for drug delivery’’ ,International Journal of Biological Macromolecules 62 (2013) 35– 43.
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