Newly Developed Anti-Dandruff Regimen, VB-3222, Delivers Enhanced Sensorial and Effective Therapeutic Benefits Against Moderate Adherent Dandruff.

BACKGROUND: Uninhibited proliferation of Malassezia spp., enhanced sebaceous gland activity and individual sensitivity are three prime etiological factors behind dandruff. For many dandruff sufferers, existing anti-dandruff products start yielding unsatisfactory results after a few cycles of use. This observation made us explore the physical and biological environment of the host and exploit the specific type of lipid dependence of Malassezia spp. for their survival. A shampoo formulation (product code VB-3222) was developed to address the shortcomings of existing therapy. PURPOSE: Evaluating efficacy of VB-3222 in comparison to marketed products through  in vitro assays and subsequently demonstrating its advantages in a clinical study. METHODS: VB-3222 was developed with a derivative of medium chain fatty acid (MCFA) and zinc pyrithione and compared against marketed comparators by in vitro time kill assay. Subsequently, VB-3222 shampoo was tested in a 21-day clinical trial on 25 moderate dandruff subjects to evaluate local safety and efficacy. RESULTS: VB-3222 in all in vitro cases demonstrated significantly better fungicidal activity than its marketed comparators. In the clinical trial, VB-3222 was well tolerated in all subjects and imparted consistent reduction of the ASFS (adherent scalp flaking score) and the pruritus score. At days 7 and 21, 55% and 90% reduction in the ASFS in comparison to treatment initiation and 50% and 95.5% reduction in the pruritus score were observed. CONCLUSION: The increased efficacy of VB-3222 over comparator products in vitro, and the dramatic reduction (>90%) in ASFS and pruritis in subjects within 21 days of use with excellent tolerability and sensorial profile, positions VB-3222 as the new generation treatment for adherent dandruff. CLINICAL TRIAL REGISTRATION NO: CTRI/2018/05/013567.

Injectable photocrosslinkable nanocomposite based on poly(glycerol sebacate) fumarate and hydroxyapatite: development, biocompatibility and bone regeneration in a rat calvarial bone defect model.

AIM: An injectable, photocrosslinkable nanocomposite was prepared using a fumarate derivative of poly(glycerol sebacate) and nanohydroxyapatite. MATERIALS & METHODS: Polymers with varying physical and mechanical properties were synthesized. Furthermore, nanocomposites were developed using a homogenization process by combining nanohydroxyapatite within poly(glycerol sebacate) matrix via photocrosslinking and evaluated both in vitro and in vivo. RESULTS & DISCUSSION: The nanocomposites were injectable, highly bioactive and biocompatible. Addition of nanohydroxyapatite led to enhanced mechanical properties with an ultimate strength of 8 MPa. The optimized nanocomposite showed good in vitro cell attachment, proliferation and differentiation of rat bone marrow-derived mesenchymal stem cells. The in vivo evaluation in a rat calvarial bone defect model showed significantly high alkaline phosphatase activity and bone regeneration. CONCLUSION: This injectable, biocompatible and bioactive in situ hardening composite graft was found to be suitable for load-bearing bone regeneration applications using minimally invasive surgery.

Doxorubicin-loaded (PEG)3-PLA nanopolymersomes: effect of solvents and process parameters on formulation development and in vitro study.

This study is focused on the preparation of doxorubicin-loaded nanopolymersomes (PolyDoxSome) and assessment of the effects of various solvents and process variables on the size and drug loading during preparation of formulation. PolyDoxSome was prepared by nanoprecipitation method using amphiphilic (PEG)3-PLA copolymer, and the formation of polymersomes was assessed by dynamic light scattering and optical and transmission electron microscopy and evaluated for in vitro release profile and in vitro cytotoxicity. A systematic investigation indicated that solvent composition, order of addition, aqueous phase, copolymer concentration, and external energy input have significant influence on size and dispersity of PolyDoxSome. Under optimized conditions, PolyDoxSome had a size range of 130-180 nm with PDI < 0.2, a zeta potential ∼-8 mV, and a drug loading at ∼11% w/w with an encapsulation efficiency at ∼53% w/w. In vitro release profile of PolyDoxSome at 37 °C demonstrated that doxorubicin release was pH dependent and gave higher release at pH 5.5 in comparison to the release at pH 7.4 (similarity factor, f2 < 50). PolyDoxSome exhibited enhanced cellular uptake of doxorubicin compared to free doxorubicin solution in MCF-7 cell line and showed a better cytotoxicity of doxorubicin at equivalent dose in nanopolymersomes. In conclusion, size and dispersity were strongly influenced by duration of magnetic stirring and overall composition of organic/aqueous media; however, size and dispersity were retained against different degrees of dilution. PolyDoxSome was able to control the release of doxorubicin in pH dependent manner and effectively deliver the drug in active form to MCF-7 breast cancer cells.

Integration of porosity and bio-functionalization to form a 3D scaffold: cell culture studies and in vitro degradation.

In this study, porous poly(lactide-co-glycolide) (PLGA) (50/50) microspheres have been fabricated by the gas-foaming technique using ammonium bicarbonate as a gas-foaming agent. Microspheres of different porosities have been formulated by varying the concentration of the gas-foaming agent (0%, 5%, 10% and 15% w/v). These microspheres were characterized for particle size, porosity and average pore size, morphology, water uptake ratio and surface area and it was found that the porosity, pore size and surface area increased on increasing the concentration of the gas-foaming agent. Further, the effect of porosity on degradation behavior was evaluated over a 12 week period by measuring changes in mass, pH, molecular weight and morphology. Porosity was found to have an inverse relationship with degradation rate. To render the surface of the microspheres biomimetic, peptide P-15 was coupled to the surface of these microspheres. In vitro cell viability, proliferation and morphological evaluation were carried out on these microsphere scaffolds using MG-63 cell line to study the effect of the porosity and pore size of scaffolds and to evaluate the effect of P-15 on cell growth on porous scaffolds. MTT assay, actin, alizarin staining and SEM revealed the potential of biomimetic porous PLGA (50/50) microspheres as scaffolds for tissue engineering. As shown in graphical representation, an attempt has been made to correlate the cell behavior on the scaffolds (growth, proliferation and cell death) with the concurrent degradation of the porous microsphere scaffold as a function of time.

Surface modified poly(L-lactide-co-epsilon-caprolactone) microspheres as scaffold for tissue engineering.

P-15 modified poly(L-lactide-co-epsilon-caprolactone) (PLCL) microspheres were investigated as scaffolds for tissue engineering applications. PLCL copolymer was synthesized by ring opening polymerization and was composed of a soft matrix of mainly epsilon-caprolactone moieties and hard domains containing more of L-lactide units thus exhibiting a rubber like elasticity responsible for providing mechanical strength to scaffolds. Microspheres were fabricated by solvent evaporation method and surface modified with P-15, a synthetic analogue of collagen. These were then evaluated for cell adhesion, ECM formation and cell proliferation. Anchorage dependent cell lines LLCPK-1 and L6 were seeded on PLCL microspheres (unmodified surface activated microspheres) and P-15-PLCL microspheres (P-15 modified microspheres). P-15 modified microspheres showed significantly higher cell adhesion and viability than unmodified microspheres. Scanning electron microscopy also revealed copious amount of extra-cellular matrix production by P-15. Initial results of cell culture experiment on two different cell lines suggested that the growth of LLCPK-1 in a 3D environment with P-15 modified microspheres is via spreading and flattening on the surface of scaffold followed by formation of a sheet-like structure while L6 grew in the form of multilayered structures with formation of interparticulate cellular bridges. The 3D moldable nature, combined with modification of surface chemistry with cell adhesion molecules such as P-15 to enhance proliferation of epithelial cells and myoblasts, recommends further investigation of P-15-PLCL microspheres for production of an ideal scaffold for soft tissue engineering.