Preparation, characterization and in vivo pharmacodynamic evaluation of thymopentin loaded poly(lactide acid)/poly(lactide-co-glycolide acid) implants.
To avoid the clinical inconvenience of repeated injection of the immune modulator thymopentin (TP5), biodegradable implants comprising a mixed polymer matrix of poly(lactide acid) (PLA) and poly(lactide-co-glycolide acid) (PLGA) were produced using a simple extrusion method. Drug release from these TP5-loaded implants was characterized both in vitro and in vivo. Pharmacodynamic studies were carried out in immunosuppressed rats using the ratio of CD4(+)/CD8(+) cells, determined by flow cytometry, as an index of immunity. The results indicated that the entrapment efficiency of the implants was greater than 98%, but the release rate of TP5 depended on the drug loading. Implants containing less than 10% TP5 showed consistent release over 30 days, with low burst-release both in vitro and in vivo. Improved immunity and survival rates were observed in rats treated by TP5 injection and in rats given middle-to-high dose implants. When the release of TP5 exceeded 0.1 mg/kg body weight/day the CD4(+)/CD8(+) ratios increased in the 3 weeks after implantation, reaching a maximum (91.6% of the normal level) by the end of the third week. The TP5-loaded implants presented here provide a promising alternative to injections and the results support the further development of controlled-release TP5 formulations.
Wei
Gang
G
School of Pharmacy, Fudan University, Shanghai 201203, PR China.
Jin
Liang
L
Xu
Lingjie
L
Liu
Yu
Y
Lu
Weiyue
W
D000818:Animals; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004343:Drug Implants / Q000737:chemistry / Q000494:pharmacology*; D019344:Lactic Acid / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D011091:Polyesters / Q000737:chemistry / Q000494:pharmacology*; D011100:Polyglycolic Acid / Q000737:chemistry / Q000494:pharmacology*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013678:Technology, Pharmaceutical / Q000379:methods*; D016305:Thymopentin / Q000737:chemistry / Q000494:pharmacology*
D004343:Drug Implants; D011091:Polyesters; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide); D016305:Thymopentin