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Current Pharmaceutical Biotechnology

Editor-in-Chief

ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

Release Kinetics from Bio-Polymeric Nanoparticles Encapsulating Protein Synthesis Inhibitor- Cycloheximide, for Possible Therapeutic Applications

Author(s): Anita K. Verma, Kumar Sachin, Anita Saxena and H. B. Bohidar

Volume 6, Issue 2, 2005

Page: [121 - 130] Pages: 10

DOI: 10.2174/1389201053642349

Price: $65

Abstract

Cycloheximide, a protein synthesis inhibitor, was encapsulated in cross-linked gelatin nanoparticles (Type B, Bovine skin, 75 Bloom) of 168nm diameter with 26% entrapment efficiency. In-vitro release kinetics of the drug from the nanoparticles was done in phoshate buffer saline (PBS) at pH 7.4 and pH 5.8. The release kinetics showed a bi-phasic curve. Interestingly, the release of drug is approx 90% in acidic pH as compared to 50% release in neutral pH. The particle size was determined by Dynamic Light Scattering (DLS) technique, and size distribution spectra at different pH were observed to vary inversely with increase in pH. These drug loaded nanoparticles were found to be stable in whole blood showing negligible haemolysis. Cytotoxicity in HBL-100 and MCF-7, breast cancer cell lines was done in a 24-72 hrs assay, showing increased anti-tumour activity over a period of time indicating slow release. Dose dependant cytotoxicity was observed after 24 hours upto 72 hours of incubation of nanoparticles while the drug per se ( < 4μg) showed 93% toxicity within 24 hours. Phase contrast microscopy of nanoparticle-cell interaction, clearly indicated aggregation along the lipid cell-membrane. Electron Microscopy (TEM, SEM) studies revealed its size and spherical shape. The stability of the particle, the slow and controlled release of drug from the gelatin nanoparticles indicate that it is a good candidate to deliver bio-pharmaceuticals. These behave as “;intelligent” carriers for drug delivery, and can be exploited to empty their drug load in acidic medium. The paper focuses on the release kinetics of the gelatin nanoparticles that can be successfully exploited to treat solid tumors.

Keywords: colloid nanoparticles, gelatin, drug delivery, cytotoxicity, haemolysis


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