Development and In Vitro/Ex Vivo Evaluation of Lecithin-Based Deformable Transfersomes and Transfersome-Based Gels for Combined Dermal Delivery of Meloxicam and Dexamethasone.

Transfersomes (TFS) are the promising carriers for transdermal delivery of various low and high molecular weight drugs, owing to their self-regulating and self-optimizing nature. Herein, we report synthesis and characterization of TFS loaded with meloxicam (MLX), an NSAID, and dexamethasone (DEX), a steroid, for simultaneous transdermal delivery. The different formulations of TFS containing varying amounts of lecithin, Span 80, and Tween 80 (TFS-1 to TFS-6) were successfully prepared by thin-film hydration method. The size of ranged between 248 and 273 nm, zeta potential values covering from -62.6 to -69.5 mV, polydispersity index (PDI) values in between 0.329 and 0.526, and entrapment efficiency of MLX and DEX ranged between 63-96% and 48-81%, respectively. Release experiments at pH 7.4 demonstrated higher cumulative drug release attained with Tween 80 compared to Span 80-based TFS. The scanning electron microscopy (SEM) of selected formulations -1 and TFS-3 revealed spherical shape of vesicles. Furthermore, three optimized transfersomal formulations (based on entrapment efficiency, TFS-1, TFS-3, and TFS-5) were incorporated into carbopol-940 gels coded as TF-G1, TF-G3, and TF-G5. These transfersomal gels were subjected to pH, spreadability, viscosity, homogeneity, skin irritation, in vitro drug release, and ex vivo skin permeation studies, and the results were compared with plain (nontransfersomal) gel having MLX and DEX. TFS released 71.72% to 81.87% MLX in 12 h; whereas, DEX release was quantified as 74.72% to 83.72% in same time. Nevertheless, TF-based gels showed slower drug release; 51.54% to 59.60% for MLX and 48.98% to 61.23% for DEX. The TF-G systems showed 85.87% permeation of MLX (TF-G1), 68.15% (TF-G3), and 68.94% (TF-G5); whereas, 78.59%, 70.54%, and 75.97% of DEX was permeated by TF-G1, TF-G3, and TF-G5, respectively. Kinetic modeling of release and permeation data indicated to follow Korsmeyer-Peppas model showing diffusion diffusion-based drug moment. Conversely, plain gel influx was found mere 26.18% and 22.94% for MLX and DEX, respectively. These results suggest that TF-G loaded with MLX and DEX can be proposed as an alternate drug carriers for improved transdermal flux that will certainly increase therapeutic outcomes.

Microfluidic fabrication and characterization of Sorafenib-loaded lipid-polymer hybrid nanoparticles for controlled drug delivery.

Lipid polymer hybrid nanoparticles (LPHNPs) have been merged as potential nanocarriers for treatment of cancer. In the present study, LPHNPs loaded with Sorafenib (SFN) were prepared with PLGA, Lecithin and DSPE-PEG 2000 by using the bulk nanoprecipitation and microfluidic (MF) co-flow nanoprecipitation techniques. Herein, a glass capillary microfluidic device was primed to optimize the LPHNPs and compared to the bulk nanoprecipitation method. The morphological analysis of prepared LPHNPs revealed the well-defined spherical nano-sized particles in bulk nanoprecipitation method. Whereas, core shell morphology was observed in the MF method. The formulation prepared by the MF method (MF1-MF3) indicated relatively higher % EE (95.0%, 93.8% and 88.7%) and controlled release of the SFN from the particles as compared to the LPHNPs obtained by the bulk nanoprecipitation method. However, the release of SFN from all LPHNP formulation followed Higuchi model (R2 = 0.9901-0.9389) with Fickian diffusion mechanism. Fourier transform infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC) and powder X-rays diffraction (pXRD) studies depicted the compatibility of SFN with all the structural components. In addition, the colloidal stability, in vitro cytotoxicity and cell growth inhibition studies of LPHNPs also demonstrated stability in biological media, biocompatibility and safety with enhanced anti-proliferative effects than the free SFN in breast cancer and prostate cancer cells. In conclusion, LPHNPs provided a prospective platform for the cancer chemotherapy and substantially improved the knowledge of fabrication and optimization of the hybrid nanoparticles.

Development of Eudragit RS 100 Microparticles Loaded with Ropinirole: Optimization and In Vitro Evaluation Studies.

The current study aimed to develop novel pH independent microparticles loaded with ropinirole (ROP) for sustained drug release. Eudragit RS 100 was used as release retardant and microparticles were fabricated by oil-in-oil emulsion solvent evaporation method. A three-factor three-level Box-Behnken design using Design-Expert software was employed to optimize formulation variables. Ropinirole loaded microparticles were evaluated with respect to morphology, particle size, encapsulation efficiency, and in vitro release profile. Optical microscopy and SEM micrographs indicated spherical shape with smooth surface and well-defined boundary. The particle size was in the range of 98.86 to 236.29 µm, being significantly increased with increasing polymer concentration. Higher polymer load also increased the thickness of internal polymer network, which led to reduced drug loss and higher entrapment efficiency (89%). The cumulative in vitro release was found to be in the range of 54.96 to 99.36% during the release studies (12 h) following zero order release kinetics and non-Fickian diffusion pattern. The developed microparticles have the potential to sustain the release of ropinirole, which may lead to a reduction in its adverse effects and improved management of Parkinson's disease.