Release mechanisms of tacrolimus-loaded PLGA and PLA microspheres and immunosuppressive effects of the microspheres in a rat heart transplantation model
| Autor: | Takatsune Yoshida, Naoto Oku, Shunsuke Watanabe, Masashi Maeda, Hiroaki Tasaki, Hiroyuki Umejima, Ryo Kojima, Yasuyuki Higashi |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Drug Polymers Polyesters media_common.quotation_subject Pharmaceutical Science chemical and pharmacologic phenomena Absorption (skin) Pharmacology Tacrolimus chemistry.chemical_compound Polylactic Acid-Polyglycolic Acid Copolymer Pharmacokinetics Polylactic acid Animals Lactic Acid media_common Chemistry Graft Survival technology industry and agriculture Controlled release Microspheres Transplantation Drug Liberation PLGA surgical procedures operative Rats Inbred Lew Heart Transplantation Immunosuppressive Agents Polyglycolic Acid |
| Zdroj: | International Journal of Pharmaceutics. 492:20-27 |
| ISSN: | 0378-5173 |
| DOI: | 10.1016/j.ijpharm.2015.07.004 |
| Popis: | The objective of this study was to elucidate the release and absorption mechanisms of tacrolimus loaded into microspheres composed of poly(lactic-co-glycolic acid) (PLGA) and/or polylactic acid (PLA). Tacrolimus-loaded microspheres were prepared by the o/w emulsion solvent evaporation method. The entrapment efficiency correlated with the molecular weight of PLGA, and the glass transition temperature of PLGA microspheres was not decreased by the addition of tacrolimus. These results indicate that intermolecular interaction between tacrolimus and the polymer would affect the entrapment of tacrolimus in the microspheres. Tacrolimus was released with weight loss of the microspheres, and the dominant release mechanism of tacrolimus was considered to be erosion of the polymer rather than diffusion of the drug. The whole-blood concentration of tacrolimus in rats was maintained for at least 2 weeks after a single subcutaneous administration of the microspheres. The pharmacokinetic profile of tacrolimus following subcutaneous administration was similar to that following intramuscular administration, suggesting that the release and dissolution of tacrolimus, rather than the absorption of the dissolved tacrolimus, were rate-limiting steps. Graft-survival time in a heart transplantation rat model was prolonged by the administration of tacrolimus-loaded microspheres. The microsphere formulation of tacrolimus would be expected to precisely control the blood concentration while maintaining the immunosuppressive effect of the drug. |
| Databáze: | OpenAIRE |
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