Sakine Tuncay Tanrıverdi

Novel topical formulations of Terbinafine-HCl for treatment of onychomycosis.

Terbinafine hydrochloride (TBF-HCl) is an active substance that is using for treatment of onychomycosis. Onychomycosis is a fungal infection which is the most common disease of nail plate. The nail plate is a barrier which prevents effective topical treatment of ungual disorders. In this study, TBF-HCl loaded liposome and ethosome formulations and also gel form of these formulations were prepared. The formulations were characterized and in vitro and ex vivo release studies were performed. Nail characterization studies were also performed to examine the effect of formulations and experimental conditions on nail surface. As a result, all formulations can serve as efficient formulations for ungual application of TBF-HCl. By the way, the results of the accumulation studies suggested that liposome poloxamer gel formulation could be promising system for ungual drug delivery due to the better accumulation and easier application of the formulation.

Evaluation of characteristics and in vitro antioxidant properties of RSV loaded hyaluronic acid-DPPC microparticles as a wound healing system.

Resveratrol (RSV) was incorporated into microparticles by spray drying to treat chronic wounds such as diabetic ulcers. RSV was chosen due to its defense mechanisms as the formation of free radicals delays the healing process. RSV was loaded into microparticles consisting of dipalmitoylphosphatidylcholine (DPPC) and hyaluronic acid (HA), a polysaccharide naturally present within the skin, known to contribute to the healing process. Microparticles were evaluated in terms of production yield, size distribution, encapsulation efficiency, morphology, specific surface area, thermal properties and water content. Spherical and homogenous microparticles (span ≤ 2) in a size range between 20 and 30 μm were obtained with high encapsulation efficiency (≥ 97%). The effect of enzymes (hyaluronidase, phospholipase and lipase) on RSV release showed a dose-dependent pattern followed by a slow release stage. Cytotoxicity/proliferation and oxidative stress parameters (glutathione, oxidized glutathione, glutathione peroxidase, malondialdehyde, superoxide dismutase) obtained from human dermal fibroblast cell cultures revealed that formulations increased cell proliferation and the presence of RSV decreased oxidation in cells. RSV-loaded HA-DPPC microparticles appear as a promising formulation for wound healing due to synergistic effect of the ingredients.

Bio‐based topical system for enhanced salicylic acid delivery: preparation and performance of gels

New salicylic acid (SA)‐loaded gels were developed using excipients made from renewable materials, and our goal was to improve drug permeation in the topical treatment of acne vulgaris.

Wound healing effects of collagen-laminin dermal matrix impregnated with resveratrol loaded hyaluronic acid-DPPC microparticles in diabetic rats

Graphical abstract Figure. No Caption available. Abstract An alternative formulation for the treatment of diabetic foot wounds that heal slowly is a requirement in pharmaceutical field. The aim of this study was to develop a dermal matrix consisting of skin proteins and lipids with an antioxidant that will enhance healing and balance the oxidative stress in the diabetic wound area due to the high levels of glucose. Thus a novel three dimensional collagen‐laminin porous dermal matrix was developed by lyophilization. Resveratrol‐loaded hyaluronic acid and dipalmitoylphosphatidylcholine microparticles were combined with this dermal matrix. Characterization, in vitro release, microbiological and in vivo studies were performed. Spherical microparticles were obtained with a high RSV encapsulation efficacy. The microparticles were well dispersed in the dermal matrix from the surface to deeper layers. Collagenase degraded dermal matrix, however the addition of RSV loaded microparticles delayed the degradation time. The release of RSV was sustained and reached 70% after 6 h. Histological changes and antioxidant parameters in different treatment groups were investigated in full‐thickness excision diabetic rat model. Collagen fibers were intense and improved by the presence of formulation without any signs of inflammation. The highest healing score was obtained with the dermal matrix impregnated with RSV‐microparticles with an increased antioxidant activity. Collagen‐laminin dermal matrix with RSV microparticles was synergistically effective due to presence of skin components in the formulation and controlled release achieved. This combination is a safe and promising option for the treatment of diabetic wounds requiring long recovery.

Terbinafine hydrochloride loaded liposome film formulation for treatment of onychomycosis: in vitro and in vivo evaluation.

Abstract Onychomycosis is a fungal infection of nail unit that is caused by dermatophytes. Oral Terbinafine hydrochloride (TBF-HCl) is being used for the treatment of onychomycosis since 24 years. The side effects caused by the systemic application and limitations of topical administration of this drug regarding the diffusion through nail lead to the development of a new formulation based on, TBF-HCl-loaded liposome. The newly obtained film formulations were prepared and characterized via several parameters, such as physical appearance, drug content, thickness, bioadhesive properties and tensile strength. In vitro and ex vivo permeation studies were performed to select an optimum film formulation for antifungal activity to show the efficiency of formulations regarding the treatment of onychomycosis. The in vitro release percentages of drug were found 71.6 ± 3.28, 54.4 ± 4.26, 56.1 ± 7.48 and 46.0 ± 2.43 for liposome loaded pullulan films (LI-P, LII-P) and liposome loaded Eudragit films (LI-E, LII-E), respectively. The accumulated drug in the nail plates were found 31.16 ± 4.22, 24.81 ± 5.35, 8.17 ± 1.81 and 8.92 ± 3.37 for LI-P, LII-P, LI-E and LII-E, respectively, which within therapeutic range for all film formulations. The accumulated drug in the nail plate was found within therapeutic range for all film formulations. The efficacy of the selected TBF-HCl-loaded liposome film formulation was compared with TBF-HCl-loaded liposome, ethosome, liposome poloxamer gel and ethosome chitosan gel formulations. It was found that TBF-HCl-loaded liposome film formulation had better antifungal activity on fungal nails which make this liposome film formulation promising for ungual therapy of fungal nail infection.

Preparation and in vitro evaluation of melatonin-loaded HA/PVA gel formulations

Abstract Melatonin-loaded hyaluronic acid (HA) and poly(vinyl alcohol) (PVA) gels were prepared by using freeze–thaw technique and an emulsion method followed by freeze–thaw technique to produce a new synergistic system for topical application. Freeze–thaw hydrogels and emulgels were characterized by means of Fourier transform infrared spectroscopy, rheology and swelling tests. The porous structure of the hydrogels was shown by scanning electron microscopy observations and thermal properties were tested by differential scanning calorimetry measurements. Bioadhesion and in vitro release characterization of formulations were performed by texture profile analysis and dialysis bag method, respectively. The pore size of both formulations was ranging from 900 nm to 30 μm. Melatonin showed a good compatibility with the polymeric matrices as the pores were smaller for the drug-loaded systems. In vitro release studies showed that the release was improved by emulgel formulations. After 24 h, the release percentage was found to be 13.240% ± 1.094 and 15.192% ± 2.270 for hydrogel and emulgel, respectively. Emulgels had better bioadhesion properties than simple freeze–thaw samples. As a conclusion, regarding the in vitro characterization studies HA and PVA hydrogel and emulgel formulations and their lyophilized forms could be promising systems for topical application of melatonin.

Terbinafine Hydrochloride Loaded PLGA Nanoparticles for TopicalAdministration

Terbinafine hydrochloride (TBF-HCl) loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) were produced by emulsification/solvent evaporation method and were characterization for pH, size, polydispersity index, zeta potential, encapsulation efficiency and in vitro release. The effect of polymer concentration was studied. The particle size analysis indicated a unimodal particle size distribution in all systems, with a mean diameter of 229-250 nm. Polydispersity index lower than 0.2 were identified, indicating a narrow size distribution. The measured zeta potential of the NP surface was approximately −10-12 mV indicating a strong negative charge at the particles surface. In terms of encapsulation efficiency (%), high values were achieved (98%) for prepared all formulations. Drug released from loaded PLGA NPs (≈80%) was for 24 hours. By in vitro drug release studies, the formulations showed controlled release characteristics following Non-Fickian type of diffusion controlled release. It is concluded from the present investigation that PLGA NPs of TBF-HCl could be a potential alternative for the treatment of topical fungal infections.

Polysaccharide Containing Gels for Pharmaceutical Applications

Bio-derived polymers are falling into the needs of pharmaceutical formulations for topical applications due to their gelling ability. Generally, in topical delivery, as an alternative way for local and systemic application of active substances, formulations in gelling form are preferred as they have multiple advantages, e.g., minimize systemic side effects, avoid gastrointestinal irritation, prevent the metabolism of the active substance in liver, etc. The present chapter reviews bio-based polymers with special reference to polysaccharides-based hydrogels with respect to their pharmaceutical applications.

Antioxidant properties evaluation of topical astaxanthin formulations as anti-aging products

The reactive oxygen species lead to skin aging via oxidative damage that are induced by UV radiation. Therefore, topical formulations which have antioxidant effect could reduce aging level. Astaxanthin is an antioxidant substance.

Prolonged skin retention of clobetasol propionate by bio-based microemulsions: a potential tool for scalp psoriasis treatment

Abstract Novel effective and cosmetically acceptable formulations are needed for the treatment of scalp psoriasis, due to the poor efficacy of the current products. The challenge in developing safe, efficient, and convenient delivery systems for this drug was addressed in the present work by formulating clobetasol propionate-loaded W/O microemulsions (MEs). Pseudo-ternary phase diagrams were constructed by using a combination of biocompatible and biodegradable excipients. Characterization studies demonstrated that selected MEs had suitable technological features such as being Newtonian fluids, possessing low viscosity, and high thermodynamic stability. Photomicrographs showed a significant alteration of the skin structure after treatment with MEs, and a preferential concentration of these in the stratum corneum and epidermis. These data, together with ex vivo permeation results, suggested an enhanced topical targeted effect due to an increased drug retention efficacy in the upper skin layers, as desired. Moreover, the bio-based excipients selected could contribute to the healing of the psoriatic scalp. In this way, the improvement of clobetasol efficacy is combined with the useful properties of the microemulsion components and with environmental safety.