Preparation and characterization of pH- and temperature-sensitive pullulan microspheres for controlled release of drugs.
Most part of pH- and temperature-sensitive microspheres used for the controlled delivery of drugs are not biodegradable. Therefore, the aim of this work is to prepare pH- and temperature-sensitive microspheres from biodegradable and biocompatible natural polymers. Pullulan microspheres were prepared by suspension cross-linking with epichlorohydrin of an aqueous solution of the polymer. In order to confer them temperature sensitivity, poly(N-isopropylacrylamide-co-acrylamide) was grafted onto pullulan microspheres. Then, the pH-sensitive units (-COOH) were introduced by reaction between the remaining -OH groups of the pullulan with succinic anhydride. The grafted pullulan microspheres are more hydrophilic than pullulan microspheres, their swelling degree as well as water regain increase significantly. The thermo-sensitivity of the carboxylated microspheres depends to the number and the ionization form (-COOH/-COO(-)) of carboxylic groups. At a low exchange capacity (0.35 meq/g), microspheres are thermo-sensitive both in the protonated and deprotonated form of -COOH groups. At a higher exchange capacity (2.25 meq/g), microspheres are almost unswellable in the protonated form and swell extensively in the ionized form (up to 28 times than their dried form) loosing in a great extent the thermo-sensitive properties. In isotonic phosphate buffer pH=7.4, both thermo-sensitive and pH/thermo-sensitive microspheres possess a phase transition temperature close to that of the human body temperature. Loading and release profiles of lysozyme, taken as a molecular model system, were investigated.
Fundueanu
Gheorghe
G
Department of Pharmaceutical Sciences, University of Ferrara, I-44100 Ferrara, Italy. ghefun@icmpp.ro
Constantin
Marieta
M
Ascenzi
Paolo
P
D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D016503:Drug Delivery Systems / Q000379:methods; D005936:Glucans / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry; D013696:Temperature
D004337:Drug Carriers; D005936:Glucans; D004364:Pharmaceutical Preparations; C009109:pullulan