Development and Characterization of Spray Dried Microparticles for Pulmonary Delivery of Antifungal Drug

Abstract

Invasive pulmonary aspergillosis is a life threatening fungal infection mainly caused by Aspergillus species. Available treatment strategy against pulmonary aspergillosis is having very limited applicability, due to its toxicity and low circulation half-life. Pulmonary drug delivery is one of the strategies that can minimize these pitfalls. In the present study, polymeric and lipidic nanoparticles of amphotericin B were prepared by spray drying technique using hydroxypropylmethylcellulose (HPMC) and stearylamine with oleic acid respectively. Formulations were characterized for particle size, zeta potential, entrapment efficiency, in-vitro release studies, uptake analysis and in-vivo bio distribution studies. Developed polymeric and nanostructured lipid carriers (NLCs) were found in submicron size (600-700nm) and spherical in shape. Studies suggested that NLCs have better entrapment efficiency (77.1±5.5 %) as compared to HPMC carrier (71.28±5.22 %). Both formulations provided sustained drug release (HPMC, 82.05% releases up to 32 hrs and NLC, 88.2 % up to 40 hrs) and reduced dose dumping that may be helpful to reduce the toxicity and improve patient compliance. In-vitro antifungal studies suggested that stearylamine formulations exhibited better antifungal activity over control and HPMC formulations. Pharmacokinetic and organ distribution studies also support our hypothesis i.e. localized drug delivery for prolong period, improving the therapeutic effectiveness of the encapsulated drug against pulmonary aspergillosis. Studies suggested that drug delivery by pulmonary route is beneficial for local action in lungs.

Lipid Systems for the Delivery of Amphotericin B in Antifungal Therapy

“…AmB-loaded NLCs prepared from Sta and OA were developed for pulmonary delivery yielding spray-dried microparticles suitable for dry powder inhaler [203]. This formulation provided sustained drug release (88.2% up to 40 h), achieving localized action in the lungs, and reduced drug nephrotoxic side effects after pulmonary administration to rats, according to pharmacokinetic parameters, organ distribution studies, histopathology, and hematological data [203].…”

Preparation and Characterization of Spherical Amorphous Solid Dispersion with Amphotericin B

“…To avoid the conventional routes of administration and to enhance the local drug bioavailability, another alternative is found by inhalation AmB particles to target local action in the lungs. A recent study has showed interest in using a pulmonary route for administering microparticles and lipid complexes [19]. The results showed a good pulmonary deposition and a lower rate of active substance in the kidney leading to a reduction of drug nephrotoxicity and an improvement of fungal activity, approximately 1.5-times better than the marketed intravenous preparations.…”

“…The results showed a good pulmonary deposition and a lower rate of active substance in the kidney leading to a reduction of drug nephrotoxicity and an improvement of fungal activity, approximately 1.5-times better than the marketed intravenous preparations. Pharmacokinetic and organ distribution studies showed that the pulmonary administration may be favorable for a good efficiency by local action [19].…”

A Novel Topical Spray Formulation for Ginkgo Bioloba for Antifungal Activity

“…They are formulated as sprays, creams, solutions, ointment, shampoos, vaginal tablets, oral medicines, and injections [3]. The duration of treatment depends on kind of fungal infection, health problems of the infected patient, problems associated with immune system and types of formulations.…”