Facile methodology of nanoemulsion preparation using oily polymer for the delivery of poorly soluble drugs.

Aqueous solubility of an active pharmaceutical ingredient (API) is a determining factor that has a direct impact on formulation strategies and overall bioavailability. Fabrication of nanoemulsions of poorly soluble drugs is one of the widely utilized approaches to overcome this problem. However, thermodynamic instability and tedious manufacturing processes of nanoemulsions limit their clinical translation. Therefore, this study was focused on circumventing the abovementioned hurdles by utilizing the polymer as an oil phase, instead of conventional oils. The nanoemulsion was prepared via a facile low-energy nanoprecipitation method using renewable poly(δ-decalactone) (PDL), as an oil phase and Pluronic F-68 as surfactant. The prepared nanoemulsions were characterized in terms of size, drug encapsulation efficiency, stability, and toxicity. Five different hydrophobic drugs were utilized to evaluate the drug delivery capability of the PDL nanoemulsion. The prepared nanoemulsions with sizes less than 200 nm were capable to enhance the aqueous solubility of the drugs by 3 to 10 times compared with the well-established Pluronic F-68 micelles. No phase separation or significant changes in size and drug content was observed with PDL nanoemulsions after high-speed centrifugation and 3 months of storage at two different temperatures (20 °C and 50 °C). PDL nanoemulsions were found to be non-heamolytic up to concentrations of 1 mg/mL, and the cell cytotoxicity studies on MDA-MB-231 and MEF cells suggest a concentration and time-dependent toxicity, where the PDL polymer itself induced no cytotoxicity. The results from this study clearly indicate that the PDL polymer has a tremendous potential to be utilized as an oil phase to prepare stable nanoemulsions via a facile methodology, ultimately favouring clinical translations. Graphical abstract TOC graphic.

Multiphase matrix of silica, culture medium and air for 3D mammalian cell culture.

The craving for multiphase materials with adjustable properties for mammalian cell encapsulation persists despite intensive research on 3D cell culture and tissue engineering. This interest is incited by the complex interaction between cells and different materials, various manufacturing methods, cell chip applications, and the aspiration to abolish animal experiments. This study aims to show the feasibility of preparing a stable multiphase material for prolonged mammalian cell embedment and 3D cell culture. The material comprises silica as the solid phase, cell culture medium with serum as the main liquid phase and air as the gas phase. The silica sol-cell culture medium-serum mixture was foamed, and it turned into a stable foamed hydrogel. The stability, flow properties and foaming parameters were studied by rheological and surface tension measurements. The viability of embedded cells was studied by measuring the metabolic activity at different time points. Their sensitivity to the surrounding conditions was compared to cells grown in monolayers by exposing them to a toxic compound. A stable foamed hydrogel with cell culture medium as the main liquid phase was prepared. Based on oscillatory measurements, the foamed hydrogel stays stable for at least 6-7 weeks and the embedded mammalian cells remain viable for the same time period. Appropriate surface tension and viscosity were crucial for an at least twofold volume increase by foaming, which is necessary for the mammalian cells to survive and proliferate. A test with a toxic compound reveals a difference in the sensitivity of cells in monolayer cultures versus embedded cells.