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Surface Characterisation of Bioadhesive PLGA/Chitosan Microparticles Produced by Supercritical Fluid Technology

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ABSTRACT

Purpose

Novel biodegradable and mucoadhesive PLGA/chitosan microparticles with the potential for use as a controlled release gastroretentive system were manufactured using supercritical CO2 (scCO2) by the Particle Gas Saturated System (PGSS) technique (also called CriticalMixTM).

Methods

Microparticles were produced from PLGA with the addition of mPEG and chitosan in the absence of organic solvents, surfactants and crosslinkers using the PGSS technique. Microparticle formulations were morphologically characterized by scanning electron microscope; particle size distribution was measured using laser diffraction. Microparticle surface was analyzed using X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) to evaluate the presence of chitosan on the surface. Mucoadhesiveness of the microparticles was evaluated in vitro using a mucin assay employing two different kinds of mucin (Mucin type III and I-S) with different degrees of sialic acid contents, 0.5–1.5% and 9–17%, respectively.

Results

The two analytical surface techniques (XPS and ToF-SIMS) demonstrated the presence of the chitosan on the surface of the particles (<100 μm), dependent on the polymer composition of the microparticles. The interaction between the mucin solutions and the PLGA/chitosan microparticles increased significantly with an increasing concentration of mucin and chitosan.

Conclusions

The strong interaction of mucin with the chitosan present on the surface of the particles suggests a potential use of the mucoadhesive carriers for gastroretentive and oral controlled drug release.

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Abbreviations

ASES:

aerosol solvent extraction system

BSA:

bovine serum albumin

CAN-BD:

supercritical carbon dioxide assisted nebulisation with a bubble dryer

FAT:

fixed analyzer transmission

GAS:

gas anti-solvent

mPEG:

methoxy polyethylene glycol

PAS:

periodic acid-Schiff

PCA:

precipitation with a compressed fluid anti-solvent

PEO:

polyethylene oxide

PGSS:

particle gas saturated system

PLA:

polylactic acid

PLGA:

poly(lactic-co-glycolic acid)

PSD:

particle size distribution

RESS:

rapid expansion from a supercritical solution

RESOLV:

rapid expansion of a supercritical solution into a liquid solvent

SAA:

supercritical assisted atomization

SAS:

supercritical anti-solvent

scCO2 :

supercritical carbon dioxide

SCF:

supercritical fluid

SEDS:

solution enhanced dispersion of solids

TMC:

N-trimethyl chitosan

ToF-SIMS:

time-of-flight secondary ion mass spectrometry

VMD:

volume-averaged mean diameter

XPS:

X-ray photoelectron spectroscopy

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ACKNOWLEDGMENTS

The authors thank Tamsin Gamble (Critical Pharmaceuticals Ltd.) for PGSS technical support and Nikolaidi Dimitra (School of Pharmacy, University of Nottingham) for valuable help with the XPS characterization.

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Authors and Affiliations

  1. Department of Drug and Health Sciences, University of Urbino “Carlo Bo”, Urbino P.zza Rinascimento 6, Urbino, 61029, Italy

    Luca Casettari & Enzo Castagnino

  2. Drug Delivery and Tissue Engineering Division, School of Pharmacy, University of Nottingham, Nottingham, NG7 2RD, UK

    Snjezana Stolnik

  3. School of Chemistry, University of Nottingham, Nottingham, NG7 2RD, UK

    Steven M. Howdle

  4. Critical Pharmaceuticals Limited, BioCity, Pennyfoot Street, Nottingham, NG1 1GF, UK

    Andrew Lewis, Steven M. Howdle & Lisbeth Illum

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  1. Luca Casettari
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  2. Enzo Castagnino
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  4. Andrew Lewis
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Correspondence to Lisbeth Illum.

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Casettari, L., Castagnino, E., Stolnik, S. et al. Surface Characterisation of Bioadhesive PLGA/Chitosan Microparticles Produced by Supercritical Fluid Technology. Pharm Res 28, 1668–1682 (2011). https://doi.org/10.1007/s11095-011-0403-z

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  • DOI: https://doi.org/10.1007/s11095-011-0403-z

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