Improvement of Antiamoebic Activity of Rokitamycin Loaded in Chitosan Microspheres

Abstract

Rokitamycin is a new macrolide containing 16 carbon atoms, strongly inhibitory for Acanthamoeba castellanii, an opportunistic protozoa of humans which cause primarily amoebic keratitis and chronic, but fatal, amoebic granulomatous meningoencephalitis. Chitosan microspheres were prepared as carriers to obtain a controlled release of rokitamycin, able to improve the antiamoebic activity of this drug. The microparticles were in vitro characterised and the efficacy of rokitamycin alone and encapsulated into microspheres on the growth rate of Acanthamoeba castellani was evaluated. The results obtained suggest that spray-drying is a good technique for the preparation of microspheres loaded with rokitamycin. The loading of the drug into the polymeric network leads to an increase in the dissolution rate compared to drug raw material and improves and prolongs the in vitro antiamoebic activity of the drug. Thus, microspheres based on rokitamycin could be used in the therapy of systemic and topical infections caused by Acanthamoeba.

New chitosan derivatives for the preparation of rokitamycin loaded microspheres designed for ocular or nasal administration

“…The composition of the microspheres and details of the spray drying feed solutions used are presented in Tables 1a and 1b. Starting from the formulation based on Cb tested in a previous work, 6 which was able to improve the antiamoebic activity of rokitamycin, obtained from a 1.0% (w/v) feed solution using a drug-polymer ratio of 1-3, a new series of loaded microspheres containing Cb was prepared. The effect of the concentration of the feed solution and of the drug-polymer ratio to the in vitro characteristics of the microparticles were tested to find the optimal preparative parameters for obtaining microspheres suitable for ocular or nasal administration.…”

“…6 In brief, an exact amount of microspheres was weighed and dissolved in a small volume of DMSO. Then, potassium phosphate buffer (pH 6.5) was added and the solution was kept under magnetic stirring for 10 min.…”

“…6,34 The chromatographic separation of RK was performed using a Hypersil BDS C18, 5 mm, 150 mm  4.6 mm (ID) stationary phase, coupled with a Hypersil C18 precolumn. The mobile phase consisted of acetonitrile and 0.05 M ammonium acetate in the ratio of 3-2 (v/v) at 1.5 mL/min flow.…”

“…5 Recent studies have shown that the loading of rokitamycin in chitosan microspheres improves and prolongs the in vitro antiamoebic activity of rokitamycin compared with the nonencapsulated drug. 6 This could be useful both in the case of ocular application to treat amoebic keratitis and in nasal administration as an alternative route for the drug administration to the brain in GAE therapy induced by Acanthamoeba.…”

“…The loading of rokitamycin in the chitosan microspheres improved and prolonged the in vitro antiamoebic activity of the drug. 6 Starting from the formulation tested, a first series of six formulations based on chitosan were prepared by spray drying, changing the feed solution concentration (1.5%, 0.5% and 0.25% (w/v)) and using the same drug-polymer ratios (1-3 and 1-4). The study further investigated the preparative parameters and compared the different formulations obtained regarding their suitability for ocular or nasal administration.…”