Evaluation of the efficacy of transdermal drug delivery of calcipotriol plus betamethasone versus tacrolimus in the treatment of vitiligo.

BACKGROUND: Vitiligo is a common pigmentary disorder affecting about 1% of the general population. There are numerous medical and surgical treatments. Microneedling is an evolving treatment technique for an expanding number of dermatologic conditions. It is used also to augment transdermal drug delivery through pores created in the stratum corneum. AIM: To evaluate the efficacy of microneedling with tacrolimus versus its efficacy with calcipotriol plus betamethasone in vitiligo treatment. METHODS: Twenty-five patients having vitiligo were selected and their symmetrical patches were divided into side A (right side) which received microneedling with dermapen and topical calcipotriol plus betamethasone and side B (left side) which received microneedling and topical tacrolimus. Every patient received a session every 2 weeks for a maximum 6 months (12 sessions) and follow-up for 3 months. Skin biopsies were taken before and after the treatment to evaluate the clinical results. RESULTS: On side A, 60% of the patients showed excellent improvement while 32% showed excellent response on side B. The mean percentage of improvement was significantly higher on side A than side B (P = 0.017* ). It was effective in the most resistant sites of vitiligo such as: elbows, knees, extremities, and acral area. Histopathological examination showed a significant expression of HMB45 on side A more than side B (P = 0.005* ). CONCLUSION: The combination of microneedling with calcipotriol plus betamethasone is more effective than its combination with tacrolimus. They are both effective in resistant sites. Both methods are safe, cheap, and good tolerated office techniques with minimal side effects.

Rapid-prototyped PLGA/ß-TCP/hydroxyapatite nanocomposite scaffolds in a rabbit femoral defect model.

Bone tissue engineering scaffolds composed of poly(d,l-lactide:glycolide) (DL-PLGA) and ß-tricalcium phosphate (ß-TCP) nanocomposites were prepared and characterized. Scaffolds with two specific architectures were produced via fused deposition modeling (FDM), a type of extrusion freeform fabrication. Microfilaments deposited at angles of 0° and 90° were designated as the 'simple' scaffold architecture, while those deposited at angles alternating between 0°, 90°, 45° and -45° were designated as the 'complex' scaffold architecture. In addition, the simple and complex scaffolds were coated with hydroxyapatite (HA). The surface morphology of the scaffolds was assessed before and after HA coating and uniform distribution of HA coating on the surface was observed by scanning electron microscopy. The scaffolds were implanted into rabbit femoral unicortical bone defects according to four treatment groups based on pore structure and HA coating. After 6 and 12 weeks, scaffolds and host bone were recovered and processed for histology. Data suggest that all configurations of the scaffolds integrated with the host bone and were biocompatible and thus may offer an exciting new scaffold platform for delivery of biologicals for bone regeneration.

Design of tenofovir-UC781 combination microbicide vaginal gels.

Tenofovir (TFV) is a proven microbicide when administered topically as a vaginal gel. To improve its efficacy, TFV was combined with the nonnucleoside reverse-transcriptase inhibitor UC781 in a vaginal gel. Mixture design of experiments theory was used to define a range of gel compositions with varying rheological properties and to assess in vitro drug release and tissue retention. Experiments and computations led to the specification of three different gels referred to as a spreading gel (SG), an intermediate spreading gel (ISG), and a bolus gel (BG). These three gels, all containing 1.0% TFV and 0.1% micronized UC781, were evaluated for in vitro release, in vitro tissue retention and safety, and in vivo pharmacokinetics in the rabbit. There were some differences in in vitro release rates of UC781 (the higher the gel viscosity, the slower the release rate) across gels, while release of TFV was independent of gel type. In an organotypic human vaginal-ectocervical (VEC) tissue model, the amounts of tissue-associated TFV and UC781 were several orders of magnitude higher than their in vitro half-maximal inhibitory concentration. There were no differences in VEC tissue concentrations of TFV or UC781 between the SG, ISG, and BG. All three gels were well tolerated in the VEC model as assessed by tissue viability, electrical resistance, histology, and cytokine (interleukin-8 and interleukin-1 beta) release. The local vaginal tissue concentrations in rabbits following a single dose or seven once-daily doses were variable and generally lower than those found in the VEC tissue model. The approach described herein provides a rational schema to design and evaluate vaginal gels for use as microbicides.

A hot-melt extruded intravaginal ring for the sustained delivery of the antiretroviral microbicide UC781.

Microbicide intravaginal rings (IVRs) are a promising woman-controlled strategy for preventing sexual transmission of human immunodeficiency virus (HIV). An IVR was prepared and developed from polyether urethane (PU) elastomers for the sustained delivery of UC781, a highly potent nonnucleoside reverse transcriptase inhibitor of HIV-1. PU IVRs containing UC781 were fabricated using a hot-melt extrusion process. In vitro release studies of UC781 demonstrated that UC781 release profiles are loading dependent and resemble matrix-type, diffusion-limited kinetics. The in vitro release methods employed over predicted the in vivo release rates of UC781 in rabbits. Accelerated stability studies showed good chemical stability of UC781 in prototype formulations, but surface crystallization of UC781 was observed following long-term storage at higher UC781 loadings, unless formulated with a polyvinylpyrrolidone/glycerol surface coating. Mechanical stability testing of prototype rings showed moderate stiffening upon storage. The PU and UC781 had minimal to no impact on viability, tissue integrity, barrier function, or cytokine expression in the tissue irritation model, and UC781 was shown to be delivered to and permeate through this tissue construct in vitro. Overall, UC781 was formulated in a stable PU IVR and provided controlled release of UC781 both in vitro and in vivo.

Co-extrusion of biocompatible polymers for scaffolds with co-continuous morphology.

A methodology for the preparation of porous scaffolds for tissue engineering using co-extrusion is presented. Poly(epsilon-caprolactone) is blended with poly(ethylene oxide) in a twinscrew extruder to form a two-phase material with micron-sized domains. Selective dissolution of the poly(ethylene oxide) with water results in a porous material. A range of blend volume fractions results in co-continuous networks of polymer and void spaces. Annealing studies demonstrate that the characteristic pore size may be increased to larger than 100 microm. The mechanical properties of the scaffolds are characterized by a compressive modulus on the order of 1 MPa at low strains but displaying a marked strain-dependence. The results of osteoblast seeding suggest it is possible to use co-extrusion to prepare polymer scaffolds without the introduction of toxic contaminants. Polymer co-extrusion is amenable to both laboratory- and industrial-scale production of scaffolds for tissue engineering and only requires rheological characterization of the blend components. This method leads to scaffolds that have continuous void space and controlled characteristic length scales without the use of potentially toxic organic solvents.