title: Development and in vitro evaluation of alginate gel-encapsulated, chitosan-coated ceramic nanocores for oral delivery of enzyme.
abstract: The successful administration of protein and peptide drugs by oral route maintaining their active conformation remains a key challenge in the field of pharmaceutical technology. In the present study, we propose the use of a nanosize ceramic core-based system for effective oral delivery of acid-labile model enzyme, serratiopeptidase (STP). Ceramic core was prepared by colloidal precipitation and sonication of disodium hydrogen phosphate solution and calcium chloride solution at room temperature. The core was coated with chitosan under constant stirring and Fourier-Transform Infra Red Spectroscopy (FTIR) confirmed phosphoric groups of calcium phosphate linked with ammonium groups of chitosan in the nanoparticles; then the enzyme was adsorbed over the preformed nanocore. Protein-loaded nanocore was further encapsulated into alginate gel for enzyme protection. Prepared system was characterized for size, shape, loading efficiency, and in vitro release profile (pH 1.2 and pH 7.4). The effect of processing variables on the size of the core was evaluated to form small, uniform, and discrete nanocores. Stability and integrity of enzyme during processing steps was assessed by in vitro proteolytic activity. The prepared system was examined to be spherical in shape with diameter 925 +/- 6.81 nm using TEM. The in vitro release data followed the Higuchi model, showing a low amount (26% +/- 2.4%) of diffusion-controlled drug release (R(2) = 0.9429) in acidic buffer up to a period of 2 to 6 hours, signifying the integrity of alginate gel in acid. In the alkaline medium sustained and nearly complete first order release of protein was observed up to a 6 hours. It is inferred that the protein-loaded ceramic core acts as a reservoir of the adsorbed enzyme and alginate gel provides protection to STP for controlled release in intestinal pH when compared to the enzyme solution.
authors.affiliation: Institute of Pharmacy, Pt Ravishankar Shukla University, Raipur (C.G.), India.
authors.forename: Manju
authors.initials: M
authors.lastname: Rawat
authors.forename: Deependra
authors.initials: D
authors.lastname: Singh
authors.forename: Shailendra
authors.initials: S
authors.lastname: Saraf
authors.forename: Swarnlata
authors.initials: S
authors.lastname: Saraf
mesh_terms: D000464:Alginates / Q000737:chemistry*; D002130:Calcium Phosphates / Q000737:chemistry; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D004798:Enzymes / Q000008:administration & dosage*; D005782:Gels; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D054118:Nanospheres; D010316:Particle Size; D010447:Peptide Hydrolases / Q000008:administration & dosage / Q000737:chemistry; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000464:Alginates; D002130:Calcium Phosphates; D004337:Drug Carriers; D004798:Enzymes; D005782:Gels; D006603:Hexuronic Acids; C494369:calcium phosphate, dihydrate; D020723:Glucuronic Acid; D048271:Chitosan; D010447:Peptide Hydrolases; C022640:serratiopeptidase