Wheat germ agglutinin-conjugated chitosan-Ca-alginate microparticles for local colon delivery of 5-FU: development and in vitro characterization.
The aim of this work was to prepare lectin-conjugated chitosan-Ca-alginate microparticles (MPs) loaded with acid-resistant particles of 5-fluorouracil (5-FU) for efficient local treatment of colon cancer. MPs were prepared by a novel one-step spray-drying technique and after wheat germ agglutinin (WGA) conjugation, they were characterized for size, swelling behavior, surface charge, entrapment efficiency and in vitro drug release. Prepared particles were spherical, with 6.73 microg/mg of WGA conjugated onto their surface. The size and zeta potential increased after conjugation, from 6.6 to 14.7 microm and from 9.6 to 15.3 mV, while drug encapsulation was 75.6 and 72.8%, respectively after conjugation. The swelling behavior of beads was mainly determined by properties of the cross-linked chitosan-alginate network. In vitro drug release studies carried out in simulated in vivo conditions with respect to pH, confirmed the potential of the particles to release the drug in a controlled manner. Also, the drug release was not significantly affected by WGA conjugation. The retention of biorecognitive activity of WGA after covalent coupling to MPs was confirmed by haemagglutination test. Functionalized MPs showed excessive mucoadhesiveness in vitro, due to the positive surface charge, pH-dependent swelling of the matrix and lectin-sugar recognition.
Glavas Dodov
M
M
Institute of Pharmaceutical Technology, Faculty of Pharmacy, University Ss Cyril and Methodious, Vodnjanska 17, P.O. Box 36, 1000 Skopje, Macedonia. magl@ff.ukim.edu.mk
Calis
S
S
Crcarevska
M S
MS
Geskovski
N
N
Petrovska
V
V
Goracinova
K
K
D000327:Adsorption; D000464:Alginates / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D002021:Buffers; D002118:Calcium / Q000737:chemistry; D002614:Chelating Agents / Q000737:chemistry; D048271:Chitosan / Q000737:chemistry* / Q000378:metabolism; D003110:Colonic Neoplasms / Q000188:drug therapy; D003692:Delayed-Action Preparations / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D004339:Drug Compounding / Q000379:methods; D005472:Fluorouracil / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D006384:Hemagglutination; D006801:Humans; D020100:Hydrogels / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008863:Microspheres; D009077:Mucins / Q000378:metabolism; D010316:Particle Size; D012995:Solubility; D013499:Surface Properties; D013552:Swine / Q000378:metabolism; D014909:Wheat Germ Agglutinins / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure
D000464:Alginates; D000964:Antimetabolites, Antineoplastic; D002021:Buffers; D002614:Chelating Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D020100:Hydrogels; D009077:Mucins; D014909:Wheat Germ Agglutinins; D048271:Chitosan; D002118:Calcium; D005472:Fluorouracil