Minocycline Hydrochloride Controlled-release Microsphere Preparation Process Optimization Based on the Robust Design Method.

OBJECTIVES: The objective of the present study is to establish a robust preparation method that could steadily produce minocycline hydrochloride (MCH) microspheres regardless of used polymer types. MATERIALS AND METHODS: Taguchi's Robust Experimental Design methodology was employed to optimize the process parameters for MCH-loaded poly(D,L-lactide-co-glycolide) (PLGA) microspheres. In the experimental design, seven controllable factors, i.e., preparation method, pH of the aqueous phase, volume of the aqueous phase, volume of dichloromethane, rotation speed, temperature, and amount of polyvinyl alcohol, were considered for the optimization of process parameters. PLGA types with different lactide/glycolide ratios were considered the uncontrollable (noise) factor. Based on the L18 orthogonal array, 18 experimental runs were conducted for each type of PLGA. The encapsulation efficiency (EE) and in vitro release rate were evaluated for all the prepared formulations. RESULTS: Regardless of the PLGA type with different lactic/glycolic acid ratios, microspheres prepared via the solid-in-oil-in-water (S/O/W) method, showed a much higher EE and faster drug release than the microspheres prepared via the co-solvent method. Preparation methods, pH of the aqueous phase, and volume of the aqueous phase were the most influencing parameters on the EE. The confirmation experiment results indicated that the signal-to-noise ratio increased by 5.76 db from that of an initial condition. The release of minocycline was fastest with the PLGA (50:50) microspheres, followed by PLGA (75:25) and PLGA (85:15). CONCLUSION: Although the interaction between the selected factors in the evaluation was ignored, the orthogonal array design of the experiment based on Taguchi's robust experimental design methodology was sufficient to optimize the process parameters for the PLGA microspheres of MCH. The S/O/W was the main factor affecting the EE. Microspheres prepared via the S/O/W method exhibited a higher EE and faster drug release than the microspheres prepared via co-solvent method. The pH and volume of the aqueous phase were also effective parameters on the EE. A robust experimental design has been successfully applied to the optimization of the process parameters for microsphere preparation.

Composite nanofibers incorporating alpha lipoic acid and atorvastatin provide neuroprotection after peripheral nerve injury in rats.

Despite the new treatment strategies within the last 30 years, peripheral nerve injury (PNI) is still a worldwide clinical problem. The incidence rate of PNIs is 1 in 1000 individuals per year. In this study, we designed a composite nanoplatform for dual therapy in peripheral nerve injury and investigated the in-vivo efficacy in rat sciatic nerve crush injury model. Alpha-lipoic acid (ALA) was loaded into poly lactic-co-glycolic acid (PLGA) electrospun nanofibers which would release the drug in a faster manner and atorvastatin (ATR) loaded chitosan (CH) nanoparticles were embedded into PLGA nanofibers to provide sustained release. Sciatic nerve crush was generated via Yasargil aneurism clip with a holding force of 50 g/cm2. Nanofiber formulations were administered to the injured nerve immediately after trauma. Functional recovery of operated rat hind limb was evaluated using the sciatic functional index (SFI), extensor postural thrust (EPT), withdrawal reflex latency (WRL) and Basso, Beattie, and Bresnahan (BBB) test up to one month in the post-operative period at different time intervals. In addition to functional recovery assessments, ultrastructural and biochemical analyses were carried out on regenerated nerve fibers. L-929 mouse fibroblast cell line and B35 neuroblastoma cell line were used to investigate the cytotoxicity of nanofibers before in-vivo experiments. The neuroprotection potential of these novel nanocomposite fiber formulations has been demonstrated after local implantation of composite nanofiber sheets incorporating ALA and ATR, which contributed to the recovery of the motor and sensory function and nerve regeneration in a rat sciatic nerve crush injury model.

Nanofibers: New Insights for Drug Delivery and Tissue Engineering.

Nanofibers became one of the major research areas for drug delivery and tissue engineering applications in the last decade. Depending on the simplicity of the preparation method and high drug loading capacity, nanofibers provide many advantages for therapeutic perspectives. In addition, combined systems such as embedding nanoparticles into the nanofiber structures provide a second option for delivery of dual active ingredients in the same formulation. The release rate of the active ingredients can also be modified easily by the formulation parameters depending on the desired release time for treatment. Nanofibers systems are used for the delivery of antibiotics, anticancer drugs, analgesics, hemostatic agents and various proteins for tissue engineering purposes. In addition, various applications such as medical device coating also provide new insights for the clinical use of nanofibers. The most commonly used technique for preparation of nanofibers is the electrospinning, which provides feasibility background for scale up process from laboratory to the industrial applications. The main boundary for nanofibers is the limitations for systemic route. Nanofibers are mainly designed for the delivery of active ingredients for local purposes. Regardless of the therapeutic aim, nanofibers are also perfect 3 dimensional structures that are suitable for tissue regeneration. They provide matrix structure for cell regeneration especially in applications for wound healing. This review is mainly focused on the recent advances on the preparation of nanofibers, applications for drug delivery, tissue engineering and wound healing purposes.