Proliposome and Prosurfactosome Formulations for Pulmonary Drug Delivery

Abstract

This study aims to compare the efficiency of conventional liposomes and surfactant-enriched vesicles (surfactosomes) using the hydrophilic drug salbutamol sulphate (SBS) and the hydrophobic drug beclometasone dipropionate (BDP) for pulmonary delivery via nebulisation.
Initially liposomes and surfactosomes with or without cholesterol were prepared using thin film method and were compared for their VMD, span and drug entrapment. Their drug retention on extrusion through 5µm, 2µm, 1µm and 0.4µm polycarbonate membrane using mini-extruder was also studied. It was observed that liposomes were more stable than surfactosome.
Particulate based proliposome technology was also used to study their potential for generating stable and inhalable dispersions. Mannitol was used as the carbohydrate carrier and on hydration; proliposomes and prosurfactosomes have generated liposomes and surfactosomes respectively. The VMD, span and zeta potential of the vesicles, and drug entrapment and drug retention on extrusion were studied. It was seen that lower proportions of SBS were entrapped using proliposome technology; hence, further extrusions through 5µm and 2µm were avoided. In vesicle with BDP, inclusion of cholesterol has decreased the drug entrapment and crystallisation of mannitol was observed.
Nebulisation of liposomes and surfactosomes with and without cholesterol was studied using PARI LC sprint air jet nebuliser, Aeroneb pro and Beurer iH50 vibrating mesh nebulisers. Two stage (Twin) impinger was used to study the potential suitability of the generated vesicles for inhalation. VMD, span and zeta potential of vesicles before and after nebulisation was studied. BDP delivery and retention in both stages of the twin impinger was also studied. It was found that surfactosomes without cholesterol delivered maximum BDP to the twin impinger. Nebulisers suitable for all four formulations were also studied. Beurer iH50 delivered maximum BDP via liposomes with and without cholesterol, Aeroneb Pro delivered maximum BDP via surfactosomes with cholesterol to upper impinger while PARI LC sprint delivered maximum BDP via surfactosomes with cholesterol. VMD and span of aerosols generated from all three nebulisers were also studied.
Stability of liposomes and surfactosomes prepared using proliposome technology was studied. VMD, span, zeta potential and BDP retention before and after spray drying and freeze drying were investigated. It was concluded that liposomes and surfactosomes were equally stable when spray drying was used whereas liposomes were more stable that surfactosomes when freeze drying was conducted. X-ray diffraction, scanning electron microscopy and transmission electron microscopy were used to analyse the characteristics of proliposomes and prosurfactosomes. A reduction in size and crystallinity was observed after spray drying and freeze drying of the formulations. Stability was also studied on storing proliposome and prosurfactosome in different environmental conditions like 5-6°C, room temperature and 40°C for a period of 3 months. It was concluded that both proliposomes and surfactosomes were most stable in 2-8°Cwhereas least stable in 40°C. Proliposomes were more stable than prosurfactosomes regardless of the storage temperature.
Formulation and characterisation of novel prosurfactosomes and comparing it with conventional liposomes for pulmonary drug delivery is the novelty of this thesis.