Oral delivery of spray dried PLGA/amifostine nanoparticles

Abstract

Amifostine (Ethyol, WR-2721) is a cytoprotective drug approved by the US Food & Drug Administration for intravenous administration in cancer patients receiving radiation therapy and certain forms of chemotherapy. The primary objective of this project was to develop orally active amifostine nanoparticles using spray drying technique. Two different nanoparticle formulations (Amifostine-PLGA (0.4:1.0 and 1.0:1.0)) were prepared using a Buchi B191 Mini Spray Dryer. A water-in-oil emulsion of amifostine and PLGA (RG 502) was spray dried using an airflow of 600 L h(-1) and input temperature of 55 degrees C. A tissue distribution study in mice was conducted following oral administration of the formulation containing drug-polymer (0.4:1.0). The efficiency of encapsulation was 90% and 100%, respectively, for the two formulations while the median particle sizes were 257 and 240 nm, with 90% confidence between 182 and 417 nm. Since amifostine is metabolized to its active form, WR-1065, by intracellular alkaline phosphatase, the tissue levels of WR-1065 were measured, instead of WR-2721. WR-1065 was detected in significant amounts in all tissues, including bone marrow, jejunum and the kidneys, and there was some degree of selectivity in its distribution in various tissues. This work demonstrates the feasibility of developing an orally effective formulation of amifostine that can be used clinically.

Radioprotection in mice following oral delivery of amifostine nanoparticles

“…In our earlier report (Pamujula et al 2004a), we also demonstrated that following oral administration of amifostine nanoparticles in mice, significant levels of WR-1065 (the active metabolite of amifostine, WR 2721) were detected in all of the key tissues analyzed. This is only one of very few reports on in vivo testing of amifostine oral formulation.…”

“…The nanoparticles were prepared by spray drying the mixture in a Bū chi B191 Mini Spray Dryer (Zurich, Switzerland), with a standard 0.7 mm nozzle (Pamujula et al 2004a). The freeze dried nanoparticles were stored refrigerated until dosing.…”

“…Based upon an extensive and critical evaluation of various such formulation strategies applicable to amifostine, we developed a biodegradable Poly (DL-lactic/glycolic acid) (PLGA)-based slow-release nanoparticle formulation of amifostine that could be administered orally and yet be effective biologically. We reported recently on the development and physicochemical characterization of such a formulation (Pamujula et al 2004a). The focus of this report is on the evaluation of the radioprotective properties of the formulation.…”

Oral delivery of low molecular weight heparin microspheres prepared using biodegradable polymer matrix system

“…Thermal analysis of the components was performed by DSC (DSC Q 100, TA instruments, New Castle, Delaware) to assess any possible interaction between the formulation components. The procedure followed for the experiment was described earlier (Pamujula et al 2004). In brief, $5 mg of the samples (LMWH, BSA, papain and a physical mixture of these three components) were weighed and crimped into an aluminum pan.…”

Current Analytical Methods Used in the In Vitro Evaluation of Nano-Drug Delivery Systems

“…The second phase encompasses the drug that is released as a result of degradation of the matrix. Emulsion-solvent evaporation, precipitation method, high pressure emulsification solvent evaporation method [11] and spray drying [12] are the most generally used methods of preparation of nanoparticles. Nanoparticles are also prepared by precipitation method using crosslinkers or ionic neutralization method.…”