Skin Retention Research Articles

Skin pigmentation improvement with resveratrol microemulsion gel using polyoxyethylene hydrogenated castor oil

Objective To investigate the safety and efficacy of resveratrol microemulsion gel in improving pigmentation. Methods Resveratrol microemulsion gel was prepared by the microemulsion solubilization method, and its quality was evaluated. The transdermal and drug retention rates of resveratrol in vivo were assessed using a transdermal test. The inhibitory effects of resveratrol suspension and microemulsion on tyrosinase activity and melanin production of A375 human melanocytes and zebrafish embryos were compared. A skin patch test was used to investigate the safety of the gel on 15 volunteers. Results The microemulsion gel was homogeneous and stable. Compared with suspension and microemulsion, the drug penetration rate and skin retention in the microemulsion gel group were significantly increased. Compared with the suspension group, the activity of melanocyte tyrosinase in A375 human melanocyte was significantly inhibited in the microemulsion group, and the melanin production rate of A375 human melanocyte and the melanin area of zebrafish yolk was decreased. All 15 volunteers tested negative for the human skin patch. Conclusions The microemulsion gel could significantly enhance the ability of resveratrol to inhibit the formation of melanin without causing side effects. These data provide the experimental basis for developing and applying the preparation for improving pigmentation.

Water-responsive gel extends drug retention and facilitates skin penetration for curcumin topical delivery against psoriasis

Psoriasis is a chronic inflammatory skin disease characterized by erythema, scaling, and skin thickening. Topical drug application is recommended as the first-line treatment. Many formulation strategies have been developed and explored for enhanced topical psoriasis treatment. However, these preparations usually have low viscosity and limited retention on the skin surface, resulting in low drug delivery efficiency and poor patient satisfaction. In this study, we developed the first water-responsive gel (WRG), which has a distinct water-triggered liquid-to-gel phase transition property. Specifically, WRG was kept in a solution state in the absence of water, and the addition of water induced an immediate phase transition and resulted in a high viscosity gel. Curcumin was used as a model drug to investigate the potential of WRG in topical drug delivery against psoriasis. In vitro and in vivo data showed that WRG formulation could not only extend skin retention but also facilitate the drug permeating across the skin. In a mouse model of psoriasis, curcumin loaded WRG (CUR-WRG) effectively ameliorated the symptoms of psoriasis and exerted a potent anti-psoriasis effect by extending drug retention and facilitating drug penetration. Further mechanism study demonstrated that the anti-hyperplasia, anti-inflammation, anti-angiogenesis, anti-oxidation, and immunomodulation properties of curcumin were amplified by enhanced topical drug delivery efficiency. Notably, neglectable local or systemic toxicity was observed for CUR-WRG application. This study suggests that WRG is a promising formulation for topically psoriasis treatment.

Development of Solid Lipid Nanoparticle-Loaded Polymeric Hydrogels Containing Antioxidant and Photoprotective Bioactive Compounds of Safflower (Carthamus tinctorius L.) for Improved Skin Delivery.

Safflower (Carthamus tinctorius L.) is a potent natural antioxidant because of active compounds such as quercetin (QU) and luteolin (LU). These components prevent damage to the skin caused by free radicals from UV rays. However, due to the poor solubility and transdermal permeation, the effectiveness of the compounds in showing their activity was limited. In this study, we develop solid lipid nanoparticle (SLN)-based hydrogel formulations to enhance the solubility and penetration of two bioactive compounds found in safflower petals extract (SPE). The hot emulsification-ultrasonication method was used to produce SLNs, and to obtain high antioxidant activity, 100% v/v ethanol was used in the extraction procedure. The results showed that this approach could encapsulate >80% of both QU and LU. Moreover, Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD) spectra indicated that most of the QU and LU were trapped in a lipid matrix and dispersed homogeneously at the molecular level, increasing the solubility. Additionally, SLN-hydrogel composites are able to release two lipophilic bioactive compounds for 24 h, which also demonstrated increased skin retention and penetrability of the QU and LU up to 19-fold. In vitro blood biocompatibility showed that no hemolytic toxicity was observed below 500 μg/mL. Accordingly, the formulation was considered safe for use. Sun protective factor (SPF) test shows a value above 15, showing an excellent promising application as the photoprotective agent to prevent symptoms associated with photoinduced skin aging.

Monoolein-based nanodispersions for cutaneous co-delivery of methylene blue and metformin: Thermal and structural characterization and effects on the cutaneous barrier, skin penetration and cytotoxicity

This study evaluated the potential of monoolein (MO)-based nanodispersions to promote the cutaneous co-delivery of metformin (MET) and methylene blue (MB) for the treatment of non-melanoma skin cancer. MO-based nanodispersions were obtained using Kolliphor® P407 (KP) and/or sodium cholate (CH), and characterized concerning the structure, thermal stability, ability to disrupt the skin barrier, cutaneous permeation and retention of MB and MET. Additionally, the cytotoxic effect of MO nanodispersions-mediated combination therapy using MET and MB in A431 cells was evaluated. The nanodispersions exhibited nanometric size (<200 nm) and thermal and physical stability. Small angle X-ray scattering studies revealed multiple structures depending on composition. They were able to interact with stratum corneum lipid structure, increasing its fluidity. The effect of MO-nanodispersions on topical/transdermal delivery of MB and MET was composition-dependent. Nanodispersions with low MO content (5 %) and stabilized with KP and CH (0.05–0.10 %) were the most promising, enhancing the cutaneous delivery of MB and MET by 1.9 to 2.2-fold and 1.4 to 1.7-fold, respectively, compared to control. Cytotoxic studies revealed that the most promising MO nanodispersion-mediated combination therapy using MET and MB (1:1) reduced the IC50 by 24-fold, compared to MB solution, and a further reduction (1.5-fold) was observed by MB photoactivation.

Dipeptide-1 modified nanostructured lipid carrier-based hydrogel with enhanced skin retention and topical efficacy of curcumin.

Topical administration of curcumin (CUR), a natural polyphenol with potent anti-inflammation and analgesic activities, provides a potential approach for local skin diseases. However, the drug delivery efficiency is highly limited by skin barriers and poor bioavailability of CUR. Herein, we propose hydrogel containing CUR-encapsulated dipeptide-1-modified nanostructured lipid carriers (CUR-DP-NLCs gel) to enhance topical drug delivery, and improve the topical therapeutic effect. The prepared CUR-DP-NLCs were characterized and were suitably dispersed into the Pluronic F127 hydrogel for topical application. The optimized CUR-DP-NLCs had a particle size of 152.6 ± 3.47 nm, a zeta potential of -33.1 ± 1.46 mV, an entrapment efficiency of 99.83 ± 0.14%, and a spherical morphology. X-ray diffraction (XRD) studies confirmed that CUR was successfully entrapped by the NLCs in an amorphous form. CUR-DP-NLCs gel exhibited sustained release over 48 h and significantly increased the skin retention of CUR. In vitro skin retention of CUR with CUR-DP-NLCs gel was 2.14 and 2.85 times higher than that of unmodified NLCs gel and free CUR, respectively. Fluorescence microscopy imaging revealed the formed nanoparticles accumulated in the hair follicles with prolonged retention time to form a drug reservoir. The hematoxylin-eosin staining showed that CUR-DP-NLCs gel could change the microstructure of skin layers and disturb the skin barriers. After topical administration to mice, CUR-DP-NLCs gel showed better analgesic and anti-inflammatory activities with no potentially hazardous skin irritation. These results concluded that CUR-DP-NLCs gel is a promising strategy to increase topical drug delivery of CUR in the treatment of local skin diseases.

Acil Serviste Datura Zehirlenmesi Olgu Sunumu

Datura Stramonium (DS) is a in our country; it grows wild in rural areas without the need for agriculture. DS can also be used as herbal medicine in respiratory system diseases such as asthma and bronchitis, in hemorrhoids and dermatological diseases such as eczema. It may lead to anticholinergic symptoms such as mydriasis, tachycardia, dry skin, flushing and urinary retention in humans due to its atropine content, and when it affects the central nervous system, it may cause symptoms ranging from restlessness, agitation, hallucination, convulsion to coma and death. We aimed to describe the case of the patient who was taken to the emergency department with the pre-diagnosis of altered consciousness, agitation, and psychiatric disorder, progressed with the signs of delirium and anticholinergic toxicity, was diagnosed with Datura Stramonium intoxication, was admitted to the intensive care unit after the first treatment, and was discharged with recovery.

Itraconazole-loaded microemulsions: formulation, characterization, and dermal delivery using shed snakeskin as the model membrane

Microemulsions (MEs) were developed for dermal delivery of 1% w/w itraconazole (ITZ). Solubility of ITZ in various oils was investigated and clove oil was selected as oil phase. Pseudoternary phase diagrams were constructed by titration method. The system containing clove oil as oil phase, Tween®80 as surfactant, and 1:1 mixture of water and polyethylene glycol 400 as aqueous phase provided the largest ME region. It was selected for the formulation development of ITZ-loaded MEs. Physicochemical stability was evaluated at 4 °C, room temperature (25 °C), and 45 °C for three months. In vitro permeation and retention studies were assessed using shed snakeskin as a model membrane. Antifungal activity was investigated by agar diffusion method. Results indicated that incorporation of ITZ in the selected MEs did not affect physical properties. Physicochemical data after storage periods revealed that the most suitable storage temperature was 4 °C. Skin permeation and retention data indicated that water-in-oil (w/o) ITZ-loaded MEs had superior dermal delivery of ITZ than oil-in-water (o/w) ITZ-loaded ME and ITZ-oily solution. Moreover, w/o ITZ-loaded MEs showed larger inhibition zones against C. albicans and T. rubrum than a commercial gel. Therefore, w/o ITZ-loaded MEs possibly provided effective dermal delivery and antifungal activity to treat superficial fungal infections.

Enhanced intradermal delivery of Dragon's blood in biocompatible nanosuspensions hydrogel patch for skin photoprotective effect.

Dragon's Blood is a member of the Chinese medicinal herb, having anti-oxygen and anti-inflammatory activity for the photoprotective effect. However, the poor water solubility of raw Dragon's Blood powder has limited its intradermal delivery process. In this study, we evaluated nanosuspensions to enhance intradermal delivery of Dragon's Blood exerting a photoprotective effect. The prepared nanosuspension was added to a composite hydrogel patch matrix for better skin application. In the present research, we used biocompatible materials hyaluronic acid and amino acid surfactants as nanosuspension stabilizers and agar/gelatin/sodium polyacrylate as hydrogel patch matrix. The prepared Dragon's Blood nanosuspension had a particle size of 447.0 ± 48.6nm. The micro-structures morphology and viscoelasticity characteristics by SEM and rheological testing confirmed a sufficient crosslinked hydrogel network. The skin retention amount of Dragon's Blood nanosuspension was 1.48 times of raw Dragon's Blood powder water suspension, and the skin penetration amount of Dragon's Blood nanosuspension was only about 1/3 of Dragon's Blood DMSO solution. In the UVB-irradiated HaCaT cell phototoxicity model, Dragon's Blood nanosuspension also significantly increased cell viability by about 1 time of the model group and decreased the production of reactive oxygen species about 1/2 times of model group. In vivo safety and efficiency evaluation experiment illustrated that DB-NS hydrogel patch processes have favorable safety and photoprotective effect with no skin irritancy and phototoxicity. Furthermore, DB-NS and DB-NS hydrogel patches could protect skin from UVA and UVB irritating skin reactions. Overall, our study of the combined use of biocompatible and biodegradable materials as excipients of nanosuspension and hydrogel patch could be used as an effective additive of Intradermal delivery and skin photoprotection.

Elaboration of novel gel-core oleosomes encapsulating phytoconstituent for targeted topical delivery in a vitiligo-induced mouse model: Focus on antioxidant and anti-inflammatory pathways

Berberine (BER) is a natural isoquinoline with promising antioxidant and anti-inflammatory effects. However, BER's low permeability hampers its topical utilization. This study aimed to elaborate and assess a novel hyaluronate integrated gel-core oleosomes nanovesicular system to ameliorate BER's dermal availability for targeted topical vitiligo treatment. Sodium hyaluronate and sodium oleate were selected as natural biological key components for their excellent skin-penetrating characteristics. Berberine-oleosomes (BER-OS) were prepared using a modified ethanol injection technique. Ex-vivo studies were performed using full-thickness human skin for simulating the real topical application. Also, in-vivo pharmacodynamic studies were conducted using a vitiligo-induced mice model. The antioxidant and anti-inflammatory effects were evaluated using depigmentation area scoring, biochemical, and gene-expression studies. BER-oleosomes attained a small particle size (186 ± 4) nm, high zeta potential (−36.0 ± 1.13) mV, excellent entrapment efficiency % (92.3 ± 0.67), outstanding sustained release of 45% after 24 h, and high physical stability. Ex-vivo study emphasized the significant capability of hyaluronate-integrated gel-core oleosomes to enhance BER retention in the human skin, enabling the effective local targeted treatment of vitiligo with minimal systemic side effects. Moreover, results displayed significant augmented anti-inflammatory and antioxidant actions for BER-oleosomes compared to BER-conventional gel. Interestingly, placebo-oleosomes possessed a significant intrinsic effect against vitiligo. Histological, immunohistochemical, and toxicological investigations confirmed BER-oleosome's safety and efficacy. Conclusively, novel BER-loaded gel-core oleosomes were considered a promising nano-topical targeted approach that overcomes delivery obstacles for vitiligo treatment.

Thymol-Loaded Eudragit RS30D Cationic Nanoparticles-Based Hydrogels for Topical Application in Wounds: In Vitro and In Vivo Evaluation

Natural medicines formulated using nanotechnology-based systems are a rich source of new wound-treating therapeutics. This study aims to develop thymol-loaded cationic polymeric nanoparticles (CPNPs) to enhance the skin retention and wound healing efficacy of thymol. The developed materials exhibited entrapment efficiencies of 56.58 to 68.97%, particle sizes of 36.30 to 99.41 nm, and positively charged zeta potential. In Vitro sustained release of thymol up to 24 h was achieved. Selected thymol CPNPs (F5 and C2) were mixed with methylcellulose to form hydrogels (GF5 and GC2). An In Vivo skin-retention study revealed that GF5 and GC2 showed 3.3- and 3.6-fold higher retention than free thymol, respectively. An In Vitro scratch-wound healing assay revealed a significant acceleration in wound closure at 24 h by 58.09% (GF5) and 57.45% (GC2). The potential for free thymol hydrogel, GF5, and GC2 to combat MRSA in a murine skin model was evaluated. The bacterial counts, recovered from skin lesions and the spleen, were assessed. Although a significant reduction in the bacterial counts recovered from the skin lesions was shown by all three formulations, only GF5 and GC2 were able to reduce the bacterial dissemination to the spleen. Thus, our study suggests that Eudragit RS30D nanoparticles-based hydrogels are a potential delivery system for enhancing thymol skin retention and wound healing activity.

Development and Evaluation of Ethosomes Loaded with Zingiber zerumbet Linn Rhizome Extract for Antifungal Skin Infection in Deep Layer Skin.

Skin fungal infection is still a serious public health problem due to the high number of cases. Even though medicines are available for this disease, drug resistance among patients has increased. Moreover, access to medicine is restricted in some areas. One of the therapeutic options is herbal medicine. This study aims to develop an ethosome formulation loaded with Zingiber zerumbet (L.) Smith. rhizome extract for enhanced antifungal activity in deep layer skin, which is difficult to cure. Ethosomes were successfully prepared by the cold method, and the optimized formulation was composed of 1% (w/v) phosphatidylcholine and 40% (v/v) ethanol. Transmission electron microscope (TEM) images revealed that the ethosomes had a vesicle shape with a diameter of 205.6-368.5 nm. The entrapment of ethosomes was 31.58% and could inhibit the growth of Candida albicans at a concentration of 312.5 μg/mL. Finally, the ethosome system significantly enhanced the skin penetration and retention of the active compound (zerumbone) compared with the liquid extract. This study showed that Z. zerumbet (L.) rhizome extract could be loaded into ethosomes. The findings could be carried over to the next step for clinical application by conducting further in vivo penetration and permeation tests.

Babchi Oil-Based Nanoemulsion Hydrogel for the Management of Psoriasis: A Novel Energy Economic Approach Employing Biosurfactants.

The current research aimed to assess the Babchi oil nanoemulsion-based hydrogel prepared using biosurfactants through a low-energy emulsification process for the topical management of psoriasis. The emulsification capacity and solubilities of many nanoemulsion constituents such as surfactants, co-surfactants, and oil were considered to determine the range of concentration of the constituents. Pseudoternary phase diagrams were created using the method of titration. Nanoemulgel structure, morphology, micromeritics, conductivity, and viscosity were all optimized. The assessment of the Babchi oil nanoemulgel included particle size, polydispersity index (PDI), drug content, pH, spreadability, rheological management, ex vivo drug study, 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging ability, in vitro drug release, release kinetics, and dermatokinetics. The selected ratios of the surfactant mixture (Smix) taken were 3:1. The entrapment efficiency estimated was 91.298%. The zeta potential of Babchi oil was observed to be -24.93 mV at 25 °C with water as a dispersant, viscosity as 0.887 cP, and material absorption as 0.01 nm. The size distribution of the particle was 108 nm by the intensity and the conductivity observed was 0.03359 mS/cm. The cumulative amount of Babchi oil penetrated and fluxed by nanoemulgel was considered larger (p ≤ 0.05) than the conventional formulations. Skin retention was observed to be good with decreased lag time. The formulation followed the Higuchi Korsmeyer for Fickian Peppas model for in vitro drug release studies. The oil was most effective on the epidermal layer of the skin for treatment. It was established that the Babchi oil nanoemulgel formulation had superior permeability capabilities for topical and transdermal administration and is a viable alternative to traditional formulations.

Enhanced Topical Co-delivery of Acyclovir and Lidocaine Gel Formulation Across Dermatomed Human Skin.

Acyclovir a widely used drug in the treatment of herpes simplex virus (HSV) infections and lidocaine a local anesthetic were combined in a topical gel formulation. The topical gel with Transcutol P (TP) or N-methyl 2-pyrrolidone (NMP) was prepared and tested for in vitro skin permeation across the intact and microneedle-treated human cadaver skin. The topical gels containing 5% each of acyclovir and lidocaine showed optimal pH, spreadability, and 100% drug release. The transdermal flux and skin retention of the gels were significantly higher compared to Generic 5% acyclovir ointment (Zovirax) (p < 0.001), and 5% lidocaine gel (numb gel) (p < 0.05). As expected, topical gels showed a very high increase in the skin permeation across microporated skin versus intact skin. In viral infections, skin is inflamed, and barrier integrity may be disrupted. The results of the present study are significant because the co-delivery formulation showed a very high increase in the skin permeation across intact and microporated skin (versus respective commercial formulations). The results of this study demonstrate enhanced co-delivery of acyclovir and lidocaine in a topical formulation across skin (intact or barrier compromised) for the treatment of herpes virus infections.

Curcumin-laden amphiphilic chitosan microemulsion with enhanced transdermal delivery, skin compatibility and anti-arthritic activity

Transdermal administration can avoid the first-pass effect of liver, improve the bioavailability of drugs and the adaptability of patients. However, there are still many problems, such as low load efficiency, short drug half-life, unfavorable transdermal efficiency, poor skin compatibility, which hinder the development of transdermal administration. In order to solve the above problems, amphiphilic chitosan microemulsion (AC-ME) is developed by using chitosan with hydrophilic carboxyl groups and hydrophobic long alkane chains as surfactant. AC-ME is efficient for drug loading and transdermal delivery, which is demonstrated by extremely high drug loading, improved drug stability and excellent transdermal efficiency. Specifically, the loading amount of curcumin (Cur) can reach up to 3.41 ± 0.13 mg/mL, an increase of approximately 30,000 times compared to its water solution. The light stability of Cur is improved from 43% to 75%. The transdermal process and skin retention of Cur exhibit 1.76-fold and 5.29-fold increase, respectively. Moreover, AC-ME is skin-compatible and does not damage skin structure. Finally, AC-ME can improve the therapeutic effect of Cur and exhibit superb anti-inflammatory effect in the rheumatoid arthritis (RA) model of mice. In a word, AC-ME would be a promising drug carrier for transdermal drug delivery.

Development and assessment of phospholipid-based luteolin-loaded lipid nanocapsules for skin delivery

Luteolin is an excellent flavone possessing several beneficial properties such as antioxidant and anti-inflammatory effects which are interesting for skin delivery. Development of an appropriate skin delivery system could be a promising strategy to improve luteolin cutaneous performance.So, the main aim of this work was to fabricate, characterize and evaluate phospholipid-based luteolin-loaded lipid nanocapsules for skin delivery. The influence of phospholipid/oil ratio, surfactant type and chitosan coating were investigated. The prepared formulations underwent in vitro assessment and the selected formulations were evaluated ex vivo and in vivo. The mean diameters of investigated formulations varied between 174 nm and 628 nm while zeta potential varied between −25.7 ± 4.8 mV and 6.8 ± 1.7 mV. Increasing in phospholipid/oil ratios resulted in decrease in particles size with little effect on zeta potential and drug encapsulation. Cremophor EL showed the lowest particle sizes and the highest drug encapsulation. Chitosan coating shifted zeta potential towards positive values. Structural analyses showed that luteolin is incorporated into lipid core of nanocapsules. Selected formulations (LNC4 and LNC13) exhibited sustained in vitro release and antioxidant activity. LNC13 (chitosan coated) showed higher flux (0.457 ± 0.113 µg/cm2/h), permeability (45.70 ± 11.66 *10-5 cm2/h) and skin retention (121.66 ± 7.6 µg/cm2 after 24 h) when compared to LNC4 and suspension. It also showed disordered the integrity of the stratum corneum, increased epidermal thickness and relieving most of inflammatory features in animal model. In conclusion, this study proves that lipid nanocapsules could effectively deliver luteolin into skin and then can be established as a potential system in the pharmaceutical and cosmeceutical horizons.

Development and Characterization of Mupirocin Emulgel for the Treatment of Primary and Secondary Infections in Dry Skin Conditions

Background: Dry skin conditions’ primary and secondary infections can be treated by using mupirocin topically. By overcoming the disadvantages of ointments, creams, and lotions, the goal of the formulation of mupirocin emulgel was to improve the occlusive properties of gels and topical delivery of hydrophobic drugs with favorable properties for dry skin conditions, as well as to investigate the impact of the concentration of different gelling agents (carbopol 940, carbopol 934, xanthum gum) on viscosity and the drug release of prepared. Materials and Methods: Oil, an emulsifier, a co surfactant, and three different types of gelling agents, such as Carbopol 940, Carbopol 934, and xanthum gum, were used to make the emulgel. The physical characteristics, pH measurement, spreadability, drug content, rheological study, and in vitro drug release of each prepared emulgel were evaluated. Researchers also looked at skin sensitivity, ex vivo penetration and skin retention, antibacterial effectiveness, and stability of the mupirocin emulgel formulation. Results: Excellent homogeneity, an acceptable pH, spreadability, and medication consistency were all features of newly developed emugels. The mupirocin formulation made with carbopol 934 (0.8 percent w/w), which is F4 batch, demonstrated greatest drug release at 82.54±0.39 percent and optimal viscosity at 4117.0± 0.59 among all emulgel formulations. The improved formulation had good antibacterial activity, was stable, didn’t irritate the skin, and exhibited improved retention in the skin. Conclusion: The results show that the designed mupirocin emulgel was successfully integrated into various gelling agents and that the drug release was inversely related to viscosity.

Fabrication and Characterizations of Pharmaceutical Emulgel Co-Loaded with Naproxen-Eugenol for Improved Analgesic and Anti-Inflammatory Effects.

The aim of this study was to fabricate and characterize a pharmaceutical emulgel co-loaded with naproxen/eugenol for transdermal delivery to improve the analgesic and anti-inflammatory effects and to eliminate GIT adverse reactions. Emulgel was prepared using a slow emulsification method and evaluated for physical appearance, thermodynamic stability, viscosity, pH, spreadability, extrudability, in-vitro drug release, drug content, ex-vivo permeation, drug retention studies and in-vivo studies. The emulgel exhibited good physical attributes, being thermodynamically stable with no phase separation, having excellent homogeneity, and pH 5.5 to 6.5. Slight changes in viscosity, spreadability and extrudability with respect to high temperature were observed (p > 0.05). The drug content was 96.69 ± 1.18% and 97.24 ± 1.27% for naproxen and eugenol, respectively. The maximum release of naproxen after 12 h was 85.14 ± 1.11%, whereas eugenol was 86.67 ± 1.23% from emulgel following anomalous non-Fickian mechanism. The maximum % permeation of naproxen across skin was 78.5 ± 1.30, whereas maximum % permeation of eugenol was 83.7 ± 1.33 after 12 h. The skin retention of eugenol and naproxen was 8.52 ± 0.22% and 6.98 ± 0.24%, respectively. The optimized emulgel inhibited the carrageenan induced paw edema. The pain reaction times of optimized emulgel and standard marketed product (Voltral®) were 11.16 ± 0.17 and 10.36 ± 0.47, respectively, with no statistically significant difference (p > 0.05). This study concluded that transdermal delivery of naproxen-eugenol emulgel synergized the anti-inflammatory and analgesic effects of naproxen and eugenol.

Silk peptide-hyaluronic acid based nanogels for the enhancement of the topical administration of curcumin.

The present study focused on the development of Cur-loaded SOHA nanogels (Cur-SHNGs) to enhance the topical administration of Cur. The physiochemical properties of Cur-SHNGs were characterized. Results showed that the morphology of the Cur-SHNGs was spherical, the average size was 171.37 nm with a zeta potential of −13.23 mV. Skin permeation experiments were carried out using the diffusion cell systems. It was found that the skin retention of Cur-SHNGs was significantly improved since it showed the best retention value (0.66 ± 0.17 μg/cm2). In addition, the hematoxylin and eosin staining showed that the Cur-SHNGs improved transdermal drug delivery by altering the skin microstructure. Fluorescence imaging indicated that Cur-SHNGs could effectively deliver the drug to the deeper layers of the skin. Additionally, Cur-SHNGs showed significant analgesic and anti-inflammatory activity with no skin irritation. Taken together, Cur-SHNGs could be effectively used for the topical delivery of therapeutic drugs.

Transferosomes versus transethosomes for the dermal delivery for minoxidil: Preparation and in vitro/ex vivo appraisal

Minoxidil is effective in the management of androgenic alopecia. However, a new drug delivery system is needed to maximize its efficacy and minimize side effects associated with its conventional formulation. Minoxidil was encapsulated into transferosomes and transethosomes and their particle size, polydispersity index, drug entrapment efficiency and in vitro drug release profiles were studied. Skin permeability and deposition were evaluated using rat abdominal skin. The particle size of the transethosomes (69.8 ± 1.4 to 167.4 ± 16.7 nm) was significantly smaller than that of the transferosomes (148.0 ± 0.3 to 364.2 ± 5.0 nm). Drug entrapment efficiency was significantly lower for the transethosomes (23.7 ± 3.2 to 47.2 ± 1.3%) compared to the transferosomes (77.0 ± 1.3 to 79.2 ± 0.1%). The drug release pattern was biphasic with a burst phase followed by a sustained release one. The transferosomes and transethosomes containing oleic acid had the best ability to sustain drug release. Transferosomes and transethosomes had respectively 2.84- and 3.36-fold enhancement in drug skin permeability compared with the drug hydroalcoholic solution. In addition, drug skin deposition was 28.5- and 18-fold higher in the stratum corneum and 3.6- and 6.5-fold higher in the epidermis/dermis for transferosomes and transethosomes, respectively compared with the drug hydroalcoholic solution. The transethosomes containing oleic acid had the highest permeability through the skin, highest deposition in deep skin layers and lowest deposition in stratum corneum. Transethosomes enhanced skin permeability and retention might improve minoxidil efficacy in the treatment of androgenic alopecia and reduce its side effects.

Hyaluronic Acid Micelles for Promoting the Skin Permeation and Deposition of Curcumin.

BackgroundThe poor skin permeation and deposition of topical therapeutic drugs is a major issue in topical drug delivery, improving this issue is conducive to improving the topical therapeutic effect of drugs.MethodsIn this study, octadecylamine modified hyaluronic acid (OHA) copolymer was synthesized by amide reaction technique to prepare curcumin (CUR)-loaded micelles (CUR-M) for topical transdermal administration. CUR-M was successfully prepared by dialysis, and the formulation was evaluated for particle size, zeta potential, surface morphology, entrapment effciency (EE%), drug loading (DL), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and the in vitro drug release. Additionally, in vitro skin permeation and retention, in vivo topical analgesic and anti-inflammatory activity, and skin irritation were assessed.ResultsThe mean drug loading (DL), drug entrapment efficiency (EE), hydrodynamic diameter and zeta potential of CUR-M were 8.26%, 90.86%, 165.64 nm and −26.85 mV, respectively. CUR-M was characterized by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR), it was found that there was an interaction between CUR and OHA, and CUR existed in CUR-M in an amorphous form. CUR-M exhibited sustained release in 48 h and good stability at 4 °C for 21days. CUR-M could significantly increase the skin penetration and retention of CUR and had better analgesic and anti-inflammatory activities in vivo when compared with CUR solution. Hematoxylin-eosin staining results revealed that the transdermal penetration mechanism of CUR-M might be related to the hydration of stratum corneum by HA. In addition, CUR-M showed no skin irritation to mouse skin.ConclusionCUR-M might be a promising and safe drug delivery system for the treatment of topical diseases.