Single component versus hybrid naturally derived matrix for controlled nanoparticles delivery

7/23/2019 Single component versus hybrid naturally derived matrix for controlled nanoparticles delivery

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Single component versus hybrid

naturally derived matrix for

controlled nanoparticles deliverySimona Cavalu,V

asile Laslo, Florin Banica and Simona

Vicas


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Naturally derived polymers

Favorable attributes of biocompatibility, biodegradability, lowcost and ease of processing.

They are typically composed of a polymeric network that can

contain up to 99 % or higher water content. As a result, they

have typically been referred to as hydrogels, and theirswelling capability in water allows them to exhibit an

environment that resembles the highly hydrated state of

natural tissues.

Polysaccharides (composed of sugar-ring building blocks) are

suitable for tissue engineering and drug delivery matrix aswell.

Alginate, cellulose, agarose, chitosan, etc..


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Tailor made polymers

Micro (nano) particulate systems (microspheres,

microcapsules) designed for controlled, prolonged drug

delivery.

Delivery of the drug to the target site, with specificity, in the

right period f time Maintain the desire concentration at the site of interest

without untoward effects.

Of primary importance is the ability of monodisperse

microsphere formulations to eliminate initial drug burst whilemodulating the onset of steady drug release.


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Such systems offer several potential advantages over

traditional methods of administration.

First, drug release rates can be tailored to the needs of a

specific application; for example, providing a constant rate of

delivery or pulsatile release. Second, controlled release systems provide protection of

drugs, especially proteins, that are otherwise rapidly

destroyed by the body.

Finally, controlled release systems can increase patientcomfort and compliance by replacing frequent (e.g., daily)

doses with infrequent (once per month or less) injection.

Tailor made polymers


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Polymeric microspheres loading drugs

with suitable release profile according to

the requirements

Microsphere drug deliverysystems have been fabricated bya variety of techniques including :

combinations of phaseseparation or precipitation;

emulsion/solvent evaporation ;

spraying and freeze dryingmethods;

ionotropic gelation methodscombined with electrostaticdroplet generation;

chemical and thermal crosslinking.


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Various routes of drug release

from microspheres

Biodegradation of

polymer matrix


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Aim of study

The aim of this study is to develop a single component ormixed matrix (microspheres) as a controlled delivery system

for nano-selenium particles, using different formulation based

on alginate and chitosan.

To find an appropriate formulation for Se bioavailability.

Alginateis a polysaccharide derived

from brown algae, certain seaweeds or

bacteria

Chitosanis derived from chitin found in the

exoskeleton of marine crustaceans

(shrimps, crabs) as well as insects and the

cell walls of fungi


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Nano size elemental Selenium-an

ecofriendly production method

Nano-size (100-500nm) elemental selenium was produced by

using probiotic yogurt bacteria (Lactobacillus casei) in a

fermentation procedure [J. Prokisch-Debrecen,HU, 2010 -

Process for Producing Elemental Selenium Nanospheres,US

Patent 20100189634].

100- 500 nm


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Selenium is of fundamental importance to human health.

As a constituent of selenoproteins, selenium has structural andenzymatic roles, in the latter context being best-known as anantioxidant and catalyst for the production of active thyroid hormone.

strong antimicrobial and anti-carcinogenic agent against a variety ofcancers: hepatoma cells, lung cancer cells, colonic cancer cells.

Despite these various advantages, high doses of selenium can causeadverse effects

selenium requirement for adults of 40 - 80 g/day .


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Fabrication of alginate and alginate/chitosan

based microspheres with nano-Selenium

filtration lyophilization

Alginate hydrogel 1.5%

Chitosan hydrogel 2%

CaCl24%

Alginate/chitosan ratio 2:1


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Alginate-nanoSe microspheres

a b

Before and after nano-Se encapsulation

92% and 89% Efficiency of nano-selenium

entrapment in the alginate respectively

alginate/chitosan matrix determined

spectrophotometrically by measuring the

absorbance at 280 nm.


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Structural characterization of polymeric

matrices

Alginate Chitosan

1315

3424 3352 OH stretching band

2876 2880 C-H stretching band

1620 1651 amide I (C=O) asymmetrical stretching

- 1591 amide II N-H bending

1414 1430 symmetrical stretching of -COO- groups

1315 amide III N-H stretching

1030 1025 C-O-C stretching bands

Alginate Chitosan


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Structural characterization of alginate/chitosan/ nanoSe

microspheres: FTIR spectroscopy

NanoSelenium

Alginate/nanoSe Alginate/chitosan/nanoSe

The observed shifts in the frequencies

and the appearance of some new

peaks confirms that the chitosan and

sodium alginate are effectively bind

with the nanoselenium.


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Structural characterization of microspheres: XRD patterns


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XRD pattern observations

Chitosanshowed intense peaks at about 2= 10 and 20, andbroad peak 2=40ocorresponding to hydrated and anhydrouscrystals, respectively.

The chitosan molecule easily form the crystalline regions andthis may be due to the presence of plenty of -OH and -NH2groups in the chitosan structure, which could form strongerinter and intramolecular hydrogen bonds.

Alginateis usually crystalline due to strong interactionbetween the alginate chains through intermolecular hydrogenbonding 2 = 13.5o; 22oand 39o.

NanoSe strong peak 2 = 18.5o

It seems that nanoSe preserve its degree of crystallinity withrespect to the alginate/chitosan matrix, but not in singlealginate one.


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Microstructure by SEM;nanostructured texture of

the microspheres surface

Alginate/nanoSelenium microspheres (freeze dried)

Alginate/chitosan/ nanoSelenium microspheres (freeze dried)

200 m

5 m 1 m

1 m10 m

200 m

Algnate/chitosan matrix is laced with nanoselenium nanoparticles


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% cumulative selenium release in simulated gastrointestinal

solutions with pH=1.8 respectively pH= 8.1, by using Differential

Pulse Voltammetry, in a three electrode configuration.

1) Gastric fluid: Pepsin 0.1 g (from Porcine stomach mucosa), NaCl

8.5 g dissolved in 1 L deionised water and adjusted pH =1.8 with1N HCl.

2) Small /large intestine fluid: Trypsin 0.1 g (from porcine

pancreas) dissolved in 1 L deionised water and adjusted pH=8.2

with 0.3 M NaHCO3.

Evaluation of selenium release in vitro


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Calibration curve of Se using DPV

0.000 0.005 0.010 0.015 0.020 0.025 0.030 0.035 0.040 0.045

1.1x10-4

1.1x10-4

1.1x10-4

1.1x10-4

1.2x10-4

1.2x10-4

1.2x10-4

1.2x10-4

1.2x10-4

1.3x10-4

1.3x10-4

I(A)

conc (mg/mL)

Equation y = a + b*x

Adj. R-Square 0.9682

Value Standard Error

B I nt er ce pt 1. 08 01 1E -4 7 .37 53 1E- 7

B Slope 4. 58855E-4 2. 76707E-5

All electrochemical measurements were performed using a potentiostat/galvanostat equipped

with three-electrode cell and software controlled. The working electrode was a 3 mm in

diameter GCE , reference electrode was an Ag/AgCl//3M KCl and counter electrode was a Pt

wire.

0.05 A0.05 A


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Cumulative selenium release

Alginate

Alginate/chitosan Stability of alginate at low pH and

conversion of sodium alginate to

insoluble but swelling alginic acid.

Gel formation of Chitosan in acidic

environment, diffusion of drug through the gel

and finally erosion of gel taking place as a result

of dissolution of Chitosan.

Chitosan is generally insoluble at neutral or

alcalin pH. After dissolution, amino groups get

protonated and the resulted polymer becomes

positively charged.

After the first 80 min (pH 1.8), selenium release from alginate was 21%, and

from alginte/chitosan 42%, suggesting that the nanoparticles may be

primarily located at the alginate interface, according to SEM

After next 150 min (pH=8.1), cumulative release of selenium from alginate

was 20% while from alginate chitosan 35%

The release depends upon the nature of the polymer matrix as well as pH of the media.

This suggests that the drugs in the blend can be used / suitable for the basic environment of the large

intestine, colon, and rectal mucosa for which there are different emptying times.


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Summary We have developed and compare two naturally derived matrices for

selenium controlled delivery.

Alginate and alginate/chitosanbased microspheres with nano-selenium encapsulated were structurally characterized by the meansof FTIR spectroscopy, XRD pattern and SEM.

Cumulative release of selenium monitored by DPV showed a

controlled behavior of both matrices. At low pH, the release process was due primarily to nanoparticles

exposed on the surface, but after 80 min, in alcaline medium,diffusion and finally erosion.

combination of Chitosan and sodium alginate are very effective

approach to have controlled mucoadhesive drug delivery in largeintestine.

The results might be of high importance as absorption of seleniumoccurs mainly in the duodenum, caecum and colon(more than 85%).

Thank you!


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Single component versus hybrid naturally derived matrix for controlled nanoparticles delivery

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