Chloroform-injection (CI) and Spontaneous-phase-transition (SPT) are Novel Methods, Simplifying the Fabrication Liposomes

Abstract

AbstractIntricate formulation methods and/or use of sophisticated equipment limit the prevalence of liposomal dosage-forms. Simple techniques are developed to assemble amphiphiles into globular lamellae while transiting from immiscible organic to the aqueous phase. Various parameters are optimized by injecting chloroform solution of amphiphiles into the aqueous phase and subsequent removal of the organic phase. Further simplification is achieved by reorienting amphiphiles through a spontaneous phase transition in a swirling biphasic system during evaporation of the organic phase under vacuum. Although the chloroform injection yields smaller size and PDI yet spontaneous phase transition method overrides simplicity and productivity. The size distribution of liposomes and solid/solvent ratio in both or any phases of formulation show direct relation. Surface charge dependant large unilamellar vesicles with a narrow distribution have PDI <0.4 in 10 μM saline. As small and monodisperse liposomes are prerequisites in targeted drug delivery strategies. Hence the desired size distribution <200 d.nm and PDI <0.15 is obtained through serial membrane-filtration method. Phosphatidylcholine/water 4 μmol/ml is achieved at a temperature of 10°C below the phase-transition temperature of phospholipids ensuing suitability for thermolabile entities and high entrapment efficiency. Both methods furnish the de-novo rearrangement of amphophiles into globular lamellae aiding in the larger entrapped volume. The immiscible organic phase facilitates faster and complete removable of the organic phase. High cholesterol content (55.6 mol%) imparts stability in primary hydration medium at 5+3°C for 6 months in light-protected type-1 glass vial. Collectively the reported methods are novel, scalable, time-efficient yielding high productivity in simple equipment.