Novel Spray Dried Glycerol 2-Phosphate Cross-Linked Chitosan Microparticulate Vaginal Delivery System-Development, Characterization and Cytotoxicity Studies.
Chitosan microparticulate delivery systems containing clotrimazole were prepared by a spray drying technique using glycerol 2-phosphate as an ion cross-linker. The impact of a cross-linking ratio on microparticle characteristics was evaluated. Drug-free and drug-loaded unmodified or ion cross-linked chitosan microparticles were examined for the in vitro cytotoxicity in VK2/E6E7 human vaginal epithelial cells. The presence of glycerol 2-phosphate influenced drug loading and encapsulation efficacy in chitosan microparticles. By increasing the cross-linking ratio, the microparticles with lower diameter, moisture content and smoother surface were observed. Mucoadhesive studies displayed that all formulations possessed mucoadhesive properties. The in vitro release profile of clotrimazole was found to alter considerably by changing the glycerol 2-phosphate/chitosan ratio. Results from cytotoxicity studies showed occurrence of apoptotic cells in the presence of chitosan and ion cross-linked chitosan microparticles, followed by a loss of membrane potential suggesting that cell death might go through the mitochondrial apoptotic pathway.
Department of Pharmaceutical Technology, Faculty of Pharmacy, Medical University of Białystok, Mickiewicza 2c, Białystok 15-222, Poland. esz@umb.edu.pl.
Emilia
E
Szymańska
Department of Pharmaceutical Technology, Faculty of Pharmacy, Medical University of Białystok, Mickiewicza 2c, Białystok 15-222, Poland. marta.szekalska@umb.edu.pl.
Marta
M
Szekalska
Department of Synthesis and Technology of Drug, Faculty of Pharmacy, Medical University of Białystok, Kilińskiego 1, Białystok 15-089, Poland. robert.czarnomysy@umb.edu.pl.
Robert
R
Czarnomysy
Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, Ljubljana SI-1000, Slovenia. zoran.lavric@ffa.uni-lj.si.
Zoran
Z
Lavrič
Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, Ljubljana SI-1000, Slovenia. stanko.srcic@ffa.uni-lj.si.
Stane
S
Srčič
Department of Pharmaceutical Analysis, Faculty of Pharmacy, Medical University of Białystok, Mickiewicza 2d, Białystok 15-222, Poland. wmiltyk@umb.edu.pl.
Wojciech
W
Miltyk
Department of Pharmaceutical Technology, Faculty of Pharmacy, Medical University of Białystok, Mickiewicza 2c, Białystok 15-222, Poland. kwin@umb.edu.pl.
Katarzyna
K
Winnicka
chitosan; cytotoxicity; glycerol 2-phosphate; microparticles; mucoadhesiveness; spray drying
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