Sustained-release microspheres of amifostine for improved radio-protection, patient compliance, and reduced side effects

Abstract

A biweekly administration of sustained-release microsphere dosage form of amifostine, a radioprotective drug used in radiotherapy, was performed to examine the feasibility to minimize injection frequency and blood concentration-associated side effects. Model animal trials indicated that this subcutaneously injecting microspheres, 50-100 mm in diameter, achieved bi-weekly prolonged radio-protective efficacy and, at the same time, significantly reduced skin irritation than the solution form of amifostine given by the same administration route. In addition, the hypertension associated with blood concentration of amifostine was not observed in the drug-treated rats. The animals given the amifostine microspheres and amifostine showed significantly differences in white blood cell, red blood cell, hematocrit, hemoglobin and spleen tissue histopathology after exposed under a cobalt-60 g-radiation at a dose rate of 1.0 Gy/min for 6 min. The in vitro release profile of amifostine from the micropsheres showed a minor initial burst (less than 20% of total drug loading in the first day of administration), consisting with the side effects observations. The results suggest that amifostine encapsulated in sustained-release microspheres may be an ideal dosage form for prolonged radio-protective efficacy and improved patient compliance.

Chitosan-Modified PLGA Nanoparticles for Control-Released Drug Delivery

“…The cumulative release of PTX from PLGA NPs reached 66.9% after 2 h because of the presence of burst release. A strong burst release should be avoided, because it can reduce the effect of drug and may cause side effects on the human body [24,25,26,27]. Generally speaking, burst release always exists in in vitro drug release of nanoparticles prepared by nanoprecipitation, and it was caused by the adsorption of drugs on the surface of nanoparticles [23].…”

Advances of Amifostine in Radiation Protection: Administration and Delivery

“…In order to test the feasibility of reducing the injection frequency and reducing the side effects related to blood drug concentration, Hong-yu Wu et al prepared subcutaneously injectable sustained-release amifostine microspheres with a diameter of 50−100 μm by modified emulsion solvent evaporation method and administered once every 2 weeks. 85 Compared with amifostine aqueous solution administered by the same route of administration, the skin irritation was significantly reduced and the radiation protection effect was prolonged. Especially in terms of medication compliance, ideal effects were achieved from significantly reducing the frequency of injection to reducing side effects.…”

Seeking optimal management for radioactive iodine therapy-induced adverse effects

“…The main barriers limiting the applicability of amifostine have been the logistics of its use and its toxicity. [ 10 ] Similarly, for pilocarpine, the side effect rate is high (usually the result of generalized parasympathomimetic stimulation), and side effects tend to be the main reason for withdrawal. [ 11 12 ] These side effects include sweating, wheezing, abdominal cramps, lacrimation, nausea, vomiting, diarrhea, dizziness, headache, palpitations, asthenia, chills, increased urinary frequency, and rhinitis.…”