ABSTRACT
OBJECTIVE: The objective of this study was to fabricate double-walled poly(lactide-co-glycolide) (PLGA) microspheres to increase encapsulation efficiency and avoid rapid release of hydrophilic drugs such as meglumine antimoniate. METHODS: In this study, double-walled and one-layered microspheres of PLGA were prepared using the emulsion solvent evaporation technique to better control the release of a hydrophilic drug, meglumine antimoniate (Glucantime®), which is the first choice treatment of cutaneous leishmaniasis. The effect of hydrophobic coating on microspheres' size, morphology, encapsulation efficiency and drug release characteristics was evaluated. Furthermore, the presence of antimony in meglumine antimoniate made it possible to observe the drug distribution within the microspheres' cross section by means of energy dispersive X-ray spectroscopy. RESULTS: Drug distribution images confirmed accumulation of the drug within the inner core of double-walled microspheres. In addition, these microspheres encapsulated the drug more efficiently up to 87% and demonstrated reduced initial burst and prolonged release compared to one-layered microspheres. These superiorities make double-walled microspheres an optimum candidate for sustained delivery of hydrophilic drugs. CONCLUSION: Double-walled microspheres provide some advantages over traditional microspheres overcoming most of their limitations. Double-walled microspheres were found to be more efficient than their corresponding one-layered microspheres in terms of encapsulation efficiencies and release characteristics.
Subject(s)
Antiprotozoal Agents/administration & dosage , Drug Carriers/chemistry , Lactic Acid/chemistry , Meglumine/administration & dosage , Organometallic Compounds/administration & dosage , Polyglycolic Acid/chemistry , Antiprotozoal Agents/chemistry , Antiprotozoal Agents/therapeutic use , Calorimetry, Differential Scanning , Chemistry, Pharmaceutical , Drug Compounding , Drug Liberation , Hydrophobic and Hydrophilic Interactions , Leishmaniasis, Cutaneous/drug therapy , Meglumine/chemistry , Meglumine/therapeutic use , Meglumine Antimoniate , Microscopy, Electron, Scanning , Microspheres , Organometallic Compounds/chemistry , Organometallic Compounds/therapeutic use , Particle Size , Polylactic Acid-Polyglycolic Acid Copolymer , Spectrometry, X-Ray Emission , Spectroscopy, Fourier Transform Infrared , Surface PropertiesABSTRACT
Cutaneous leishmaniasis is caused by different species of Leishmania parasites and its available treatments have not yet provided a strong consistent result. The weak response of current chemotherapeutics is due to their deficient effects on stealth parasites inside macrophages, rapid clearance from the site of action and systemic side effects in high doses. Liposomal formulation of anti-leishmanial drugs could overcome these problems. In this study, different liposomal formulations of three famous anti-leishmanial drugs: Glucantime®, miltefosine and paromomycin were prepared by a modified freeze-drying double emulsion method. Liposome size, zeta potential and encapsulation efficiency were evaluated, and their imaging was carried out by means of atomic force microscopy. Three formulations were evaluated in vivo by subcutaneous injection into skin lesions caused by Leishmania major in BALB/c mice. Encapsulation efficiency of prepared liposomes was up to 90%; however, they inherited a bimodal size distribution that caused their encapsulation efficiency to decrease to 50% during filtering sterilization. Besides, the effect of surface charge was significant on preparation procedure, size and encapsulation efficiency. All three formulations reduced amastigote counts and lesion size but only miltefosine-loaded formulations had significant therapeutic effects compared with control group (p < 0.05).
