ABSTRACT
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.
Subject(s)
Alginates/chemistry , Antimetabolites, Antineoplastic/administration & dosage , Chitosan/chemistry , Drug Carriers/chemistry , Fluorouracil/administration & dosage , Microspheres , Wheat Germ Agglutinins/chemistry , Adsorption , Alginates/metabolism , Alginates/ultrastructure , Animals , Antimetabolites, Antineoplastic/chemistry , Antimetabolites, Antineoplastic/therapeutic use , Buffers , Calcium/chemistry , Chelating Agents/chemistry , Chitosan/metabolism , Colonic Neoplasms/drug therapy , Delayed-Action Preparations/metabolism , Drug Carriers/metabolism , Drug Compounding/methods , Fluorouracil/chemistry , Fluorouracil/metabolism , Fluorouracil/therapeutic use , Hemagglutination , Humans , Hydrogels/chemical synthesis , Hydrogels/chemistry , Hydrogels/metabolism , Hydrogen-Ion Concentration , Kinetics , Mucins/metabolism , Particle Size , Solubility , Surface Properties , Swine/metabolism , Wheat Germ Agglutinins/metabolism , Wheat Germ Agglutinins/ultrastructureABSTRACT
Multilamellar liposomes containing 5-fluorouracil (5-FU) were prepared by modified lipid film hydration method and were lyophilized with or without saccharose as cryoprotectant. The effect of lyophilization on the stability of liposomes was evaluated by comparing the vesicle size, encapsulation efficiency and the drug release rate before and after lyophilization/rehydration. The process of lyophilization, without cryoprotectant, resulted in particle size increase and significant content leakage. By the addition of saccharose, the lipid bilayers become more stable and less permeable to the encapsulated drug, saccharose imparted 5-FU retention of about 80% after lyophilization/rehydration. Freeze-drying did not affect the particle size of liposomes containing saccharose as cryoprotectant. The drug release profiles of rehydrated liposomes followed Higuchi's square root model. Also, the obtained release profiles were all biphasic: a rapid initial drug release phase (burst release of the portion of the drug that leaked out of liposomes during the lyophilization) was followed by a slower, approximately constant drug release phase (zero-order kinetics).
Subject(s)
Fluorouracil/pharmacokinetics , Liposomes/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacokinetics , Chemistry, Pharmaceutical/methods , Drug Carriers , Drug Stability , Fluorouracil/chemistry , Freeze Drying/methods , Particle Size , Solubility , Sucrose/chemistry , Technology, Pharmaceutical/methodsABSTRACT
Liposomal hydrogel formulations of lidocaine HCl, suitable for topical application, have been prepared and drug release properties in vitro have been evaluated. Liposomes composed of Soya lechitin and cholesterol, with lidocaine HCl, entrapped in the inner water compartment, were prepared by simple hydration method. Topical liposomal gel formulations were prepared by incorporation of liposomes into a structured vehicle (hydrogels of Carbopol 940 in concentration of 1.5, 1.75 and 2%). High percentage of encapsulated drug in liposomes has been obtained (over 70%). Liposomal gel formulations provided prolonged drug release rate. The concentration of gelling agent in a range 1.5-2.0% affected the release rate slightly. In vitro release data showed that release kinetic can be described as diffusion-controlled, while liposomes act as reservoir systems for continuous delivery of drug. Proposed formulations provided stable percentage of entrapped drug and drug release within an examination period of 3 weeks.
