Therapeutic efficacy of sustained drug release from chitosan gel on local inflammation.
The model anti-inflammatory drug prednisolone (PS) was retained in chitosan (CS) gel beads, which were prepared in a 10% aqueous amino acid solution (pH 9.0). Sustained release of PS from the CS gel beads was observed. Carrageenan solution was injected into air pouches (AP), which were prepared subcutaneously on the dorsal surface of mice, in order to induce local inflammation. CS gel beads retaining PS were then implanted into the AP to investigate the therapeutic efficacy of sustained PS release against local inflammation. In vivo PS release from CS gel beads was governed by both diffusion of the drug and degradation of the gel matrix. Sustained drug release by CS gel beads allowed the supply of the minimum effective dose and facilitated prolonged periods of local drug presence. Inflammation indexes were significantly reduced after implantation of CS gel beads when compared with injection of PS suspension. Thus, extension of the duration of drug activity by CS gel beads resulted in improved therapeutic efficacy. These observations indicate that CS gel beads are a promising biocompatible and biodegradable vehicle for treatment of local inflammation.
Kofuji
K
K
Faculty of Pharmaceutical Sciences, Hokuriku University, Ho 3, Kanagawa-machi, Kanazawa 920-1181, Japan. k-kofuji@hokuriku-u.ac.jp
Akamine
H
H
Qian
C J
CJ
Watanabe
K
K
Togan
Y
Y
Nishimura
M
M
Sugiyama
I
I
Murata
Y
Y
Kawashima
S
S
D000277:Adjuvants, Pharmaceutic / Q000737:chemistry*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D002199:Capillary Permeability / Q000187:drug effects; D002351:Carrageenan; D002686:Chitin / Q000031:analogs & derivatives* / Q000737:chemistry*; D048271:Chitosan; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004339:Drug Compounding; D005782:Gels; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011239:Prednisolone / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D012867:Skin / Q000378:metabolism; D012995:Solubility
D000277:Adjuvants, Pharmaceutic; D000893:Anti-Inflammatory Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005782:Gels; D002686:Chitin; D002351:Carrageenan; D048271:Chitosan; D011239:Prednisolone