Preparation of High-Payload, Prolonged-Release Biodegradable Poly(lactic-<i>co</i>-glycolic acid)-Based Tacrolimus Microspheres Using the Single-Jet Electrospray Method

Abstract

Tacrolimus-loaded poly(lactic-co-glycolic acid) microspheres (TAC-PLGA-M) can be administered for the long-term survival of transplanted organs due to their immunosuppressive activity. The purpose of our study was to optimize the parameters of the electrospray method, and to prepare TAC-PLGA-M with a high payload and desirable release properties. TAC-PLGA-M were prepared using the electrospray method. In vitro characterization and evaluation were performed using scanning electron microscopy, X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier-transform infrared spectroscopy. Drug-loading efficiency was greater than 80% in all formulations with a maximum loading capacity of 16.81 0.37%. XRD and DSC studies suggested that the drug was incorporated in an amorphous state or was molecularly dispersed in the microspheres. The in vitro release study showed prolonged release patterns. TAC-PLGA-M with enhanced drug loading and prolonged-release patterns were successfully prepared using the electrospray method.Key words electrospray; microsphere; poly(lactic-co-glycolic acid); prolonged release; tacrolimus Tacrolimus (TAC), a potent immunosuppressant drug, is primarily used to increase the survival time of transplanted organs.1) The immunosuppressive activity of tacrolimus is mediated through the inhibition of calcineurin, which is a protein phosphatase found in the cytoplasm of T-cells, and the subsequent blockage of interleukin-2 production, leading to a decrease in T cell proliferation.2) In clinical practice, tacrolimus is administered as a twice-daily dosing regimen. Modified-release tacrolimus with once daily administration has also been used safely.3) There are no reports regarding the use of prolonged release formulations of tacrolimus in clinical practice, although some polymer-based formulations for longterm delivery of tacrolimus have been used in animal model studies. As has been previously reported, a single dose of the new type of tacrolimus with biodegradable microspheres could keep the plasma concentration steady for two weeks, suggesting that immunosuppressive activity could be achieved with the use of polymer-based formulations.4,5) Subcutaneous injection of tacrolimus pellets, which could give a plasma concentration within the desired therapeutic window, provided effective immunosuppression for more than three months in rat model studies.6) Likewise, tacrolimus-loaded biodegradable microspheres reportedly achieved sustained release over a long period, giving flat parallel concentration profiles for 10 d from the first day after a single subcutaneous administration in liver-transplanted rats. 7)Long-term controlled delivery of drugs has been accomplished by the use of biodegradable polymeric particulate systems.8) Poly(lactic-co-glycolic acid) (PLGA) is a biodegradable polymer that undergoes hydrolysis in the body to produce two monomers: lactic acid and glycolic acid. The rate of degradation of PLGA and the release profile of drugs from PLGAbased formulations depend on the mole...

Drug-nanoencapsulated PLGA microspheres prepared by emulsion electrospray with controlled release behavior

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Potential differentiation ability of gingiva originated human mesenchymal stem cell in the presence of tacrolimus

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