Evaluation of wound healing potential of new composite liposomal films containing coenzyme Q10 and d-panthenyl triacetate as combinational treatment.

Conventional formulations can not achieve wound healing efficiently and fail to accelerate wound regeneration. To overcome these problems, it was planned to develop nanoformulations that perform a positive effect on the wound healing duration and are suitable for topical use. In this study, liposomal film formulations that encapsulated d-panthenyl triacetate (PTA) and coenzyme Q10 (CoQ10) were optimized by using response surface methodology (RSM) and were analyzed for their wound healing efficacy and cytotoxicity on fibroblast (CCD1079 Sk) and keratinocyte (HEKa) cells. Swelling index, puncture strength, and puncture deformation values, which were choosen as dependent variables for the liposomal film formulation were found as 556.9% ± 21.3, 3.98 ± 0.98 N/mm2, and 6.57% ± 1.12, respectively. Cumulative release of 65.32% for PTA and 12.23% for CoQ10 was obtained after 24 hours of in vitro release study in sink conditions. The in vitro cytotoxicity and wound healing assay results suggested that optimum formulation could be used safely on fibroblast and keratinocyte cells and provided wound closure entirely after 24 h. Consequently, the optimum liposomal film containing PTA and CoQ10 formulations could be proposed as an innovative approach in wound healing treatment, considering their release, mechanical properties, stability, and effectiveness.

Design and Evaluation of Topical Antioxidant Nanogel Formulations.

Transdermal delivery of an active substance is promising, but a challenging option is available for local and systemic effects. The prolonged residence of formulation in the skin is important for topical delivery. In this study, it was aimed to develop a formulation that can overcome the stability and absorption problems of the vitamin C active substance by preparing nanogels. Nanogel-based materials have high drug loading capacity, biocompatibility, stability, and biodegradability, which are the key points to design a topical drug delivery system. Bovine serum albumin (BSA) and chitosan (CS) were used to prepare nanogels by a simple green self-assembly technique. Prepared nanogels were successfully used to entrap vitamin C, with an entrapment ratio between 86.08% ± 1.29% and 107.93% ± 1.04%. The studies started with vitamin C analysis and continued with characterization studies such as homogeneity, pH, viscosity, rheological properties, zeta potential, polydispersity index, particle size, and in vitro dissolution studies of nanogels. The antioxidant activities of the formulations were also tested by cell culture studies. The antioxidant activities of the nanogels were also tested by in vitro 2,2-diphenyl-1-picrylhydrazyl assay. Although topical vitamin C is effective in many ways, it has a risk of serious stability and absorption problems. The present work was aimed at developing pharmaceutically optimized topical nanogel formulations of vitamin C for antioxidant effect. An optimum nanogel formulation was composed of a 1:4 ratio of CS:BSA with (F19 formulation) in terms of entrapping vitamin C, formulation homogeneity, pH, viscosity, rheological properties, zeta potential, PI, particle size, in vitro dissolution and cell culture studies. The optimized formulation showed higher antioxidant efficacy in vitro than vitamin C. In conclusion, prepared topical nanogel of vitamin C was stable and could be used with promising potential for topical application.

Propolis loaded liposomes: evaluation of antimicrobial and antioxidant activities.

Propolis, a natural bee product, has both antimicrobial/antifungal and antioxidant characteristics. Active substances having antimicrobial and antifungal effects are used to avoid infections, which develop during long treatment process of chronic wounds. Antioxidant substances protect wound areas against the effect of free radicals and accelerate the healing process. For this purpose, propolis was used to develop topical liposome formulations for wound treatment. Characterization studies (particle size distribution, polydispersity index, Zeta Potential, morphology pH, loading capacity, encapsulation efficiency, in-vitro release behaviour) as well as stability studies were performed. Then in-vitro antioxidant (free radical scavenging capacity and trolox equivalent antioxidant capacity) and antimicrobial/antifungal activities of formulations have been evaluated. The particle size of formulations was found within the range of 300-750 nm depending on the concentration of lipid and water phase in the formulation. The Zeta Potential and pH values of optimum formulation were -23.0 ± 0.666 and 6.34, respectively. Loading capacity and encapsulation efficiency were 66.535 ± 2.705% and 57.321 ± 2.448%. At the end of 8 h, 48.16% of propolis was released and the formulations were found stable during 3 months at +4 °C. Drug loaded liposome formulations significantly scavenged the ABTS+ radical in a dose-dependent manner of propolis when compared with unloaded liposome formulations (p < 0.05). The minimum inhibitory concentration (MIC) values of liposomes ranged from 512 to 128 µg/mL for bacteria and 256 to 128 µg/mL for fungi. Overall results showed that effective and innovative alternative was developed for topical application in wound treatment with propolis loaded liposomal formulations having antioxidant and antimicrobial effects.

Tazarotene-loaded in situ gels for potential management of psoriasis: biocompatibility, anti-inflammatory and analgesic effect.

Psoriasis is a chronic autoinflammatory disorder characterized by patches of abnormal skin. For psoriasis management, the application of topical retinoids as Tazarotene is recommended. However, Tazarotene could induce skin irritation limiting its use. Herein, it is evaluated the possible usage of in situ gels for tazarotene skin delivery. The topical in situ gels were developed using thermosensitive poloxamers via cold method. They were examined for their appearance, sol-gel temperature, clarity, pH, viscosity, in vitro release, and stability. Their biocompatibility was evaluated by investigating their cytotoxicity and irritation inducing capacity. The possible anti-inflammatory and analgesic activities were determined by measuring the nitric oxide and prostaglandin E2 levels production in LPS-stimulated RAW264.7 murine macrophage cells. It was revealed that the in situ gels had no cytotoxic effect (∼95-100% cell viability) and nor irritation potential (∼97% cell viability), according to the in vitro EpiDerm™ reconstituted skin irritation test. Additionally, the 10% tazarotene-in situ gels showed possible analgesic activity since the production of prostaglandin E2 (PGE2) was decreased. In further, both concentrations of 5% and 10% tazarotene-in situ gels inhibited significantly the nitrite oxide production at 16% and 19%, respectively. Finally, the prepared in situ gels can act as a potential non-irritant alternative option for tazarotene topical skin delivery.

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

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.

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

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.

Formulation and Evaluation of Organogels Containing Hyaluronan Microparticles for Topical Delivery of Caffeine.

Cellulite is a dermal disorder including the extracellular matrix, the lymphatic and microcirculatory systems and the adipose tissue. Caffeine is used as the active moiety depending its preventive effect on localization of fat in the cellular structure. Hyaluronic acid (hyaluronan-HA) is a natural constituent of skin that generates formation and poliferation of new cells having a remarkable moisturizing ability. The aim of this study is to formulate HA microparticles loaded with caffeine via spray-drying method. Resulting microparticle formulations (33.97 ± 0.3 µm, span < 2, 88.56 ± 0.42% encapsulation efficiency) were distributed in lecithin organogels to maintain the proper viscosity for topical application. Following the characterization and cell culture studies, in vitro drug release and ex vivo permeation studies were performed. The accumulated amount of caffeine was twice higher than the aqueous solution for the microparticle-loaded organogels at 24 h (8262,673 µg/cm2versus 4676,691 µg/cm2). It was related to the sustained behaviour of caffeine release from the microparticles. As a result, lecithin organogel containing HA-encapsulated microparticles could be considered as suitable candidate formulations for efficient topical drug delivery system of caffeine. In addition to that, synergistic effect of this combination appears as a promising approach for long-acting treatment of cellulite.

Dual-Prevention for UV-Induced Skin Damage: Incorporation of Melatonin-Loaded Elastic Niosomes into Octyl Methoxycinnamate Pickering Emulsions.

Incorporation of antioxidants into sunscreens is a logical approach, yet co-delivery of them with UV filters is a challenge. Here, we purposed a combination therapy, in which the chemical UV filter, octyl methoxycinnamate, was accumulated on upper skin while the antioxidant, melatonin, can penetrate deeper layers to show its effects. Melatonin-loaded elastic niosomes and octyl methoxycinnamate Pickering emulsion were prepared separately. Lyophilized elastic niosomes were dispersed into the Pickering emulsion to prepare the proposed combination formulation. The characterization studies of the formulations revealed that elastic niosomes can be prepared with tunable nanometer sizes, whereas Pickering emulsions can encapsulate the UV filter in micrometer-sized droplets. Melatonin-loaded elastic niosomes prepared with Tween80/Span80 mixture were 146 nm with a PI of 0.438, and 58.42% entrapment efficiency was achieved. The mean diameter size of the combination formulation was 27.8 µm. Ex vivo permeation studies revealed that 7.40% of octyl methoxycinnamate and 58% of melatonin were permeated through the rat skin while 27.6% octyl methoxycinnamate and 37% of melatonin accumulated in the skin after 24 h. Cell culture studies with real-time cell analyzer showed that the proposed formulation consist of melatonin-loaded elastic niosomes and octyl methoxycinnamate Pickering emulsion had no negative effect on the cell proliferation and viability. According to α,α-diphenyl-ß-picrylhydrazyl free radical scavenging method, the proposed formulation showed as high antioxidant activity as melatonin itself. It is concluded that the proposed formulation would be a promising dual therapy for UV-induced skin damage with co-delivery strategy.

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

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.

In Vivo Assessment of Clobetasol Propionate-Loaded Lecithin-Chitosan Nanoparticles for Skin Delivery.

The aim of this work was to assess in vivo the anti-inflammatory efficacy and tolerability of clobetasol propionate (CP) loaded lecithin/chitosan nanoparticles incorporated into chitosan gel for topical application (CP 0.005%). As a comparison, a commercial cream (CP 0.05% w/w), and a sodium deoxycholate gel (CP 0.05% w/w) were also evaluated. Lecithin/chitosan nanoparticles were prepared by self-assembling of the components obtained by direct injection of soybean lecithin alcoholic solution containing CP into chitosan aqueous solution. Nanoparticles obtained had a particle size around 250 nm, narrow distribution (polydispersity index below 0.2) and positive surface charge, provided by a superficial layer of the cationic polymer. The nanoparticle suspension was then loaded into a chitosan gel, to obtain a final CP concentration of 0.005%. The anti-inflammatory activity was evaluated using carrageenan-induced hind paw edema test on Wistar rats, the effect of formulations on the barrier property of the stratum corneum were determined using transepidermal water loss measurements (TEWL) and histological analysis was performed to evaluate the possible presence of morphological changes. The results obtained indicate that nanoparticle-in-gel formulation produced significantly higher edema inhibition compared to other formulations tested, although it contained ten times less CP. TEWL measurements also revealed that all formulations have no significant disturbance on the barrier function of skin. Furthermore, histological analysis of rat abdominal skin did not show morphological tissue changes nor cell infiltration signs after application of the formulations. Taken together, the present data show that the use of lecithin/chitosan nanoparticles in chitosan gel as a drug carrier significantly improves the risk-benefit ratio as compared with sodium-deoxycholate gel and commercial cream formulations of CP.

Establishment and Validation of an Automated System for the Antifactor IIa Assay: A Case Study of Potency Assessment of a Pharmaceutical Gel Formulation.

Antithrombotic agents and anticoagulant drugs, such as those from the heparin family, are employed in clinical settings for the prevention and treatment of clotting, thromboembolism, and wound healing. The potency assessment of antithrombotic agents is typically conducted using antifactor IIa assay with manual systems which are time-consuming and often lack repeatability. Here, we present a novel automated system that significantly enhances assay repeatability, attaining an outstandingly low relative standard deviation (RSD) % of only 0.6% for repeatability. This system has been applied to a pharmaceutical gel formulation for wound healing developed by Abdi Ibrahim Pharmaceuticals R&D Center as a case study for validation. The automated system demonstrated substantial improvements over manual systems in linearity (R2 = 0.9927), precision, accuracy, specificity, and robustness. The system aligns with the European Pharmacopoeia specifications, promising to enhance quality control across pharmaceutical formulations and conduct absorbance-based end-point assays within the pharmaceutical industry while offering increased throughput and cost-effectiveness.

Design of polyethylene glycol-polyethylenimine nanocomplexes as non-viral carriers: mir-150 delivery to chronic myeloid leukemia cells.

MicroRNAs (miRNAs) are acknowledged as indispensable regulators relevant in many biological processes, and they have been pioneered as therapeutic targets for curing disease. miRNAs are single-stranded, small (19-22 nt) regulatory non-coding RNAs whose deregulation of expression triggers human cancers, including leukemias, mainly through dysregulation of expression of leukemia genes. miRNAs can function as tumour suppressors (suppressing malignant potential) or oncogenes (activating malignant potential) like actors of complex diseases. To address the issue of overcoming instability and low transfection efficiency in vitro, the polyethylene glycol-polyethyleneimine (PEG-PEI) nanoparticle was used as non-viral vector carrier for miR-150 transfection, which is downregulated in chronic myeloid leukemia. PEG-PEI [PEG(550)3 -g-PEI(1800) ]/miRNA nanocomplexes were synthesised and characterised by particle size distribution (PSD), polydispersity index (PDI) and zeta potential, surface charge, their cytotoxicity, and transfection efficiency. Interaction with human leukemia cells (K-562 and KU812) and control cells NCI-BL2347 with them has been investigated. The transfection efficiency of PEG-PEI/miRNA at N/P 26 rose 6.7-fold above the control by qRT-PCR. The size of homogenous nanocomplexes (PBI < 0.5) was 160.8 ± 11 nm. The data indicate that PEG-PEI may be an encouraging non-viral carrier for altering miRNA expression in the treatment of chronic myeloid leukemia, with many advantages such as relatively high miRNA transfection efficiency and low cytotoxicity.

Investigation of different emulsion systems for dermal delivery of nicotinamide.

Nicotinamide (NA) has been shown to have beneficial effects on several skin diseases such as tumor, acne vulgaris, photodamage, cellulite and atopic dermatitis. The purpose of this study was to develop a multiple emulsion and a microemulsion formulation as delivery systems for NA. A two-step process was used to prepare the W/O/W multiple emulsion. Optimum microemulsion formulation was selected by using construction of pseudo-ternary phase diagram. The physicochemical properties such as droplet size and viscosity measurements, stability studies were also evaluated. Ex-vivo permeation studies were performed with Franz-type diffusion cells and the samples were analysed by high performance liquid chromatography (HPLC). The permeation data showed that there was no significant difference between multiple emulsion and microemulsion (p > 0.05). Transepidermal water loss (TEWL) was also measured. As a result of TEWL studies, a slight increase of TEWL values was observed for microemulsion formulation on rat skin when compared with multiple emulsion and commercial formulation. The results suggested that microemulsion and multiple emulsion formulations could be new and alternative dosage forms for topical application of NA.

A quality by design approach using artificial intelligence techniques to control the critical quality attributes of ramipril tablets manufactured by wet granulation.

Quality by design (QbD) is an essential part of the modern approach to pharmaceutical quality. This study was conducted in the framework of a QbD project involving ramipril tablets. Preliminary work included identification of the critical quality attributes (CQAs) and critical process parameters (CPPs) based on the quality target product profiles (QTPPs) using the historical data and risk assessment method failure mode and effect analysis (FMEA). Compendial and in-house specifications were selected as QTPPs for ramipril tablets. CPPs that affected the product and process were used to establish an experimental design. The results thus obtained can be used to facilitate definition of the design space using tools such as design of experiments (DoE), the response surface method (RSM) and artificial neural networks (ANNs). The project was aimed at discovering hidden knowledge associated with the manufacture of ramipril tablets using a range of artificial intelligence-based software, with the intention of establishing a multi-dimensional design space that ensures consistent product quality. At the end of the study, a design space was developed based on the study data and specifications, and a new formulation was optimized. On the basis of this formulation, a new laboratory batch formulation was prepared and tested. It was confirmed that the explored formulation was within the design space.

A novel preparation method for organogels: high-speed homogenization and micro-irradiation.

The aim of this work was to prepare organogels of Carbopol 974P NF (C974) in PEG 400 by using a novel technique, high-speed homogenization followed by microwave heating. Triclosan (TCS) was used as a model drug. C974, at concentrations ranging between 2% and 4%, was dispersed in 25 ml of PEG 400, and the dispersion was homogenised for 5 min at 24,000 rpm. The dispersion was either heated at 80°C in water bath under mechanic stirring at 200 rpm or exposed to micro-irradiation (1,200 W/1 h) for 2 min. The formulations prepared with both methods performed a well-structured gel matrix characteristic at 3% and 4% of C974 concentrations. As the concentrations of the polymer increased, the elastic properties also increased. The viscosity profiles indicated a shear-thinning system. DSC data revealed that TCS was dissolved in gel. Skin accumulation ability of TCS had been improved by these novel organogels regardless of the preparation method. TCS was still microbiologically effective after the microwave process was applied. It was determined that microwave heating is a suitable method to obtain C974 organogels. This novel production technique developed might be promising especially in industrial scale when the dramatic reduction in the preparation time and energy were considered.

Quality by design approach: application of artificial intelligence techniques of tablets manufactured by direct compression.

The publication of the International Conference of Harmonization (ICH) Q8, Q9, and Q10 guidelines paved the way for the standardization of quality after the Food and Drug Administration issued current Good Manufacturing Practices guidelines in 2003. "Quality by Design", mentioned in the ICH Q8 guideline, offers a better scientific understanding of critical process and product qualities using knowledge obtained during the life cycle of a product. In this scope, the "knowledge space" is a summary of all process knowledge obtained during product development, and the "design space" is the area in which a product can be manufactured within acceptable limits. To create the spaces, artificial neural networks (ANNs) can be used to emphasize the multidimensional interactions of input variables and to closely bind these variables to a design space. This helps guide the experimental design process to include interactions among the input variables, along with modeling and optimization of pharmaceutical formulations. The objective of this study was to develop an integrated multivariate approach to obtain a quality product based on an understanding of the cause-effect relationships between formulation ingredients and product properties with ANNs and genetic programming on the ramipril tablets prepared by the direct compression method. In this study, the data are generated through the systematic application of the design of experiments (DoE) principles and optimization studies using artificial neural networks and neurofuzzy logic programs.

Fabrication of pure-drug microneedles for delivery of montelukast sodium.

Dissolving microneedle (MN) patches are usually formulated with a blend of drug and excipients added for mechanical strength and drug stabilization. In this study, we developed MNs made of pure drug to maximize drug loading capacity. MN patches were fabricated for transdermal delivery of montelukast sodium (MS) which is used to treat asthma and allergic rhinitis. We developed three different fabrication methods - solvent casting, melt casting, and solvent washing - and determined that filling molds with MS powder followed by a solvent washing method enabled MS to be loaded selectively to the MNs. Drug localization was confirmed with Raman imaging. MNs were able to penetrate in vitro and ex vivo skin models, and maintained strong mechanical properties during 6 months' storage at 22 °C. MS was also stable and compatible with the formulation used for the patch backing layer after 3 months' storage at 40 °C. MS delivery efficiency into skin was 55%, which enabled delivery of 3.2 mg MS into porcine skin ex vivo, which is in the range of MS doses in human clinical use. We conclude that the solvent washing method can be used to prepare MNs containing pure drug, such as MS at milligram doses in a ~ 1 cm2 MN patch.

Protection of hair color with pomegranate peel extract-loaded liposomal formulation: Preparation, characterization, and ex-vivo activity studies.

BACKGROUND: Pomegranate peel extract is known as a powerful antioxidant and due to preventing oxidation, it can reduce color change of dyed hair after washing. Liposomes are vesicular systems that include lipids and can form a film on hair fibers. Delivery system and active agent have a synergistic effect on protecting hair color and reducing dyeing frequency. AIMS: This study aimed to prepare liposomes suspension as an innovative formulation of pomegranate peel extract to reduce hair color changing. METHODS: Pomegranate peel extract-loaded liposomes were prepared with lipidic film hydration method. The characterizations of formulations (F1 and F2) were defined by several parameters. The pH, particle size, polydispersity index, zeta potential, microscopical image, loading capacity (LC), and encapsulation efficiency (EE) of formulations were determined. The antioxidant capacity of formulations and actives were tested. The effect of formulations on hair color change was shown with ex-vivo studies. RESULTS: The results showed that cholesterol influenced particle size, zeta potential, and antioxidant capacity. The particle sizes of formulations were 217.71 ± 6.74 nm and 577.5 ± 1.41 nm for F1 and F2, respectively. F2 formulation had better results for zeta potential (33.8 mV) while F1 was neutral. Morphologic images confirmed vesicular structure or liposomes. The EE was found higher for F2 than F1 (F1: 57.14 and F2: 78.69). Antioxidant studies confirmed that active substance and the vesicular system had a synergistic effect on protection from oxidation. Selected formulation reduced hair color change as shown in ex-vivo tests. CONCLUSION: Pomegranate peel extract-loaded liposomes were designed for hair color protection. It was shown with this study that prepared formulations have a good color protection on hair fibers due to antioxidant properties of pomegranate peel extract and film forming effect of liposomal formulations. According to results, prepared liposomal formulations may serve as a good alternative for reducing dyeing frequency and protecting hair fibers.

Combining dexamethasone and TNF-α siRNA within the same nanoparticles to enhance anti-inflammatory effect.

We propose to combine two therapeutic anti-inflammatory approaches with different mechanisms of action in a single drug delivery system consisting of cationic dexamethasone palmitate nanoparticles (CDXP-NP) associated with TNF-α siRNA. The CDXP-NPs are obtained by the solvent emulsion evaporation technique using dexamethasone palmitate, a prodrug of dexamethasone, associated with a cationic lipid, DOTAP. Their physicochemical properties as well as their ability to bind siRNA were evaluated through gel electrophoresis and siRNA binding quantification. SiRNA cellular uptake was assessed by flow cytometry and confocal microscopy on RAW264.7 macrophages. TNF-α inhibition was determined on LPS-activated RAW264.7 macrophages. Stable and monodisperse nanoparticles around 100 nm with a positive zeta potential (+59 mV) were obtained with an encapsulation efficiency of the prodrug of 95%. A nitrogen/phosphate (N/P) ratio of 10 was selected that conferred the total binding of siRNA to the nanoparticles. Using these CDXP-siRNA-NPs, the siRNA was strongly internalized by RAW264.7 macrophage cells and localized within the cytoplasm. On the LPS-induced RAW264.7 macrophages, a larger inhibition of TNF-α was observed with CDXP-siRNA-NPs compared to CDXP-NPs alone. In conclusion, from these data, it is clear that a combination of DXP and TNF-α siRNA therapy could be a novel strategy and optimized alternative approach to cure inflammatory diseases.

Comparative Evaluation of Clinical Efficacy and Safety of Collagen Laminin-Based Dermal Matrix Combined With Resveratrol Microparticles (Dermalix) and Standard Wound Care for Diabetic Foot Ulcers.

This is an open, prospective, comparative parallel-arm medical device clinical study of Dermalix (Dx) in diabetic foot wounds. Dx is a 3-dimensional collagen-laminin porous-structured dermal matrix prepared and additionally impregnated with resveratrol-loaded hyaluronic acid and dipalmitoylphosphatidylcholine-based microparticles. The aim was to evaluate the efficacy and safety of Dx, an investigational medical device, in Wagner 1 and 2 wounds in comparison to a standard wound care (SWC) that consists of irrigation and cleaning with sterile saline solution. Forty-eight patients were randomized to receive either SWC or SWC + Dx. A 4-week treatment period was followed by a 2-month follow-up without treatment. The wound area measurement, total collagen, vascular epidermal growth factor, tumor necrosis factor, interleukin 1, caspase 3, glutathione, reduced/oxidized glutathione, and lipid peroxidation levels were evaluated. At the end of 4 weeks, the percentage closures of wounds were determined as 57.82% for Dx, and 26.63% for SWC groups. Dx had a significant effect on tumor necrosis factor, caspase 3, and reduced/oxidized glutathione levels. Dx provided 2 times faster wound healing and decreased oxidative stress. Application of Dx in the first phase of wound would help the wound area heal faster with a safe profile.