Encapsulation of docetaxel in oily core polyester nanocapsules intended for breast cancer therapy

This study is designed to test the hypothesis that docetaxel [Doc] containing oily core nanocapsules [NCs] could be successfully prepared with a high percentage encapsulation efficiency [EE%] and high drug loading. The oily core NCs were generated according to the emulsion solvent diffusion method using neutral Labrafac CC and poly(d, l-lactide) [PLA] as oily core and shell, respectively. The engineered NCs were characterized for particle mean diameter, zeta potential, EE%, drug release kinetics, morphology, crystallinity, and cytotoxicity on the SUM 225 breast cancer cell line by dynamic light scattering, high performance liquid chromatography, electron microscopies, powder X-ray diffraction, and lactate dehydrogenase bioassay. Typically, the formation of Doc-loaded, oily core, polyester-based NCs was evidenced by spherical nanometric particles (115 to 582 nm) with a low polydispersity index (< 0.05), high EE% (65% to 93%), high drug loading (up to 68.3%), and a smooth surface. Powder X-ray diffraction analysis revealed that Doc was not present in a crystalline state because it was dissolved within the NCs' oily core and the PLA shell. The drug/polymer interaction has been indeed thermodynamically explained using the Flory-Huggins interaction parameters. Doc release kinetic data over 144 h fitted very well with the Higuchi model (R2 > 0.93), indicating that drug release occurred mainly by controlled diffusion. At the highest drug concentration (5 μM), the Doc-loaded oily core NCs (as a reservoir nanosystem) enhanced the native drug cytotoxicity. These data suggest that the oily core NCs are promising templates for controlled delivery of poorly water soluble chemotherapeutic agents, such as Doc

Preparation of polycaprolactone nanoparticles via supercritical carbon dioxide extraction of emulsions

Polycaprolactone (PCL) nanoparticles were produced via supercritical fluid extraction of emulsions (SFEE) using supercritical carbon dioxide (scCO2). The efficiency of the scCO2 extraction was investigated and compared to that of solvent extraction at atmospheric pressure. The effects of process parameters including polymer concentration (0.6–10% w/w in acetone), surfactant concentration (0.07 and 0.14% w/w) and polymer-to-surfactant weight ratio (1:1–16:1 w/w) on the particle size and surface morphology were also investigated. Spherical PCL nanoparticles with mean particle sizes between 190 and 350 nm were obtained depending on the polymer concentration, which was the most important factor where increase in the particle size was directly related to total polymer content in the formulation. Nanoparticles produced were analysed using dynamic light scattering and scanning electron microscopy. The results indicated that SFEE can be applied for the preparation of PCL nanoparticles without agglomeration and in a comparatively short duration of only 1 h

Design and optimization of self-microemulsifying drug delivery system (SMEDDS) of felodipine for chronotherapeutic application

The objective of this research work was to design, develop and optimize the self micro-emulsifying drug delivery system (SMEDDS) of Felodipine (FL) filled in hard gelatine capsule coated with polymer in order to achieve rapid drug release after a desired time lag in the management of hypertension. Microemulsion is composed of a FL, Lauroglycol FCC, Transcutol P and Cremophor EL. The optimum surfactant to co-surfactant ratio was found to be 2:1. The resultant microemulsions have a particle size in the range of 65-85 nm and zeta potential value of -13.71 mV. FL release was adequately adjusted by using pH independent polymer i.e. ethyl cellulose along with dibutyl phthalate as plasticizer. Influence of formulation variables like viscosity of polymer, type of plasticizer and percent coating weight gain was investigated to characterize the time lag. The developed formulation of FL SMEDDS capsules coated with ethyl cellulose showed time lag of 5-7 h which is desirable for chronotherapeutic application

Protein-loaded poly(epsilon-caprolactone) microparticles. I. Optimization of the preparation by (water-in-oil)-in water emulsion solvent evaporation.

The aim of this work was to optimize protein entrapment in pure poly(epsilon-caprolactone) (PCL) microparticles (MP) using the (water-in-oil)-in water solvent evaporation technique and bovine serum albumin (BSA) as drug model. Therefore, the preparative variables such as polymer solvent, protein/polymer ratio, polymer molecular weight, internal aqueous/organic phases ratio, organic/external aqueous phase ratio, and nature of the emulsifier were evaluated on microparticle characteristics such as BSA entrapment, entrapment efficiency, size and morphology. The in vitro release profiles of BSA from such MP in two different media with or without sodium dodecyl sulphate (SDS) were investigated. In optimum conditions, smooth and spherical pure PCL MP with high encapsulation efficiency (50.29 +/- 5.01%) were prepared. The release profiles of BSA in the release media were significantly different and faster in the presence of SDS. Moreover, they exhibited a relatively low burst effect after 24h (<30%) followed by a continuous release over 28 days. Due to PCL's numerous desirable characteristics, such MP could be an exciting alternative for the controlled release of proteinaceous compounds

Optimization of resveratrol nanoformulation and evaluation of its cytotoxicity on cochlear derived cells

Purpose: The aim of the work is to develop resveratrol (RES)-loaded nanocarriers (NCs) intended for cochlear drug delivery. Furthermore, in vitro toxicity of the synthesized NCs is evaluated in cochlear cell lines. Methods: RES-NCs are prepared by solvent-diffusion technique without surfactant. RES, PLGA and PCL-PEG di-block are mixed in different ratios, dissolved in acetone and added dropwise to aqueous phase under constant stirring (acetone/water ratio 1/20). RES-NCs are washed twice and freeze-dried. Box-Behnken design (BBD) is used to study the influence of formulation variables on Z-size, Polydispersity index (PDI), Zeta-potential, drug encapsulation efficiency (EE%) and ratio between Z-size before and after freeze-drying (S f/Si). To increase RES-NC stability during freeze-drying, lactose, mannitol, sucrose and trehalose are tested at different concentrations (1%, 5%, 10%, 15%, 20%w/v). Finally, MTS and LDH assays are carried out to check RES and Blank NCs in vitro toxicity after 24h incubation in an organ of Corti (HEI-OC1) and a stria vascularis (SVK-1) cell lines. Results: BBD model is validated since all experimental responses fit with predicted values. Checkpoint analyses (bias 500μM) and blank NCs (>800μg/mL) affect the cell viability. Conclusion: RES-NCs are successfully synthesized and optimized by BBD. In addition, in vitro studies show that RES (<500μM) and blank NCs (< 800μg/mL) are non-toxic for HEI-OC1 and SVK-1 cells