In Vitro Release of Lysozyme from Gelatin Microspheres: Effect of Cross-linking Agents and Thermoreversible Gel as Suspending Medium

• Published in: Biomacromolecules Vol. 12; no. 9; pp. 3186 - 3193
• Main Authors: Hiwale, Pradip, Lampis, Sandrina, Conti, Gabriele, Caddeo, Carla, Murgia, Sergio, Fadda, Anna M, Monduzzi, Maura
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 12.09.2011
• Subjects: Animals; Applied sciences; Biological and medical sciences; Chickens; Cross-Linking Reagents - chemistry; Delayed-Action Preparations - chemical synthesis; Delayed-Action Preparations - metabolism; Drug Carriers - chemical synthesis; Drug Carriers - metabolism; Exact sciences and technology; Excipients - chemistry; Gelatin - chemistry; Gels - chemistry; General pharmacology; Glucose - chemistry; Glutaral - chemistry; Medical sciences; Microscopy, Electron, Scanning; Microspheres; Muramidase - analysis; Muramidase - metabolism; Natural polymers; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Phase Transition; Physicochemistry of polymers; Poloxamer - chemistry; Proteins; Spectroscopy, Fourier Transform Infrared; Temperature; Surfactant polymer; Drug carrier; Crosslink agent; Glucose; Glutaral; Gelatin; Crosslinked polymer; Microparticle; Propylene oxide copolymer; Release; Lysozyme; Enzyme; Control release polymer; Non ionic surfactant; Physical gel; Crosslinking; Particle suspension; Ethylene oxide copolymer; Experimental study; In vitro; Protein; Glycosylases; Triblock copolymer; Particle size distribution; Gelatin derivatives; Gel point; Glycosidases; Morphology; Hydrolases; Kinetics; Spherical particle; Lattice structure; Comparative study
• ISSN: 1525-7797; 1526-4602
• DOI: 10.1021/bm200679w

This study was aimed to characterize the microstructure and the performance of gelatin microspheres (GMs) cross-linked by two different cross-linkers viz. d-glucose and glutaraldehyde. New formulations were obtained, suspending the GMs in a thermoreversible Pluronic F127 (PF127) liquid-crystalline gel. Lysozyme was used as a model biomacromolecular drug to evaluate release features. Both types of cross-linked GMs were prepared by thermal gelation method. The lysozyme-loaded microspheres were characterized by scanning electron microscopy (SEM) for size distribution, shape, and surface texture. SEM revealed that both types of lysozyme-loaded GMs were spherical in shape and that the surface of glutaraldehyde cross-linked GMs was smoother than that of the glucose cross-linked GMs. The degree of cross-linking of microspheres was investigated using ATR-FTIR technique. The prepared GMs were suspended in 20% w/v aqueous PF127 gel for which the usual sol–gel transition temperature of 22 °C did not change in the presence of GMs, as indicated by rheological measurements. SAXS study of the PF127 gel confirmed the occurrence of a discrete cubic liquid-crystalline phase of the Fm3m type whose lattice parameter slightly decreased as a result of GMs addition. The in vitro release of lysozyme from both types of cross-linked GMs was successfully controlled when they were suspended in PF127 gel, thus suggesting the potential use of this new combined formulation as a drug-depot system.