Anti-aging efficacy of topical formulations containing niosomes entrapped with rice bran bioactive compounds

Context: Rice [Oryza sativa L. (Gramineae)] bran is a rich source of phytochemicals. Its oil also contains several bioactive components that exhibit antioxidative properties such as ferulic acid (F), γ-oryzanol (O), and phytic acid (P) which can be a new source of cosmetic raw materials.

Objective: To evaluate the anti-aging effects of the gel and cream containing niosomes entrapped with the rice bran bioactive compounds.

Materials and methods: The semi-purified rice bran extracts containing F, O, and P which indicated the growth stimulation of human fibroblasts and the inhibition of MMP-2 by sulforhodamine B and gelatin zymography, respectively, were entrapped in niosomes by supercritical carbon dioxide fluid (scCO₂) and incorporated in gel and cream formulations. The skin hydration, elasticity, thickness and roughness, and pigmentation in human volunteers after treated with these gel and creams were investigated by corneometer, cutometer, visiometer, and mexameter, respectively.

Results: Gel and cream containing the semi-purified rice bran extracts entrapped in niosomes gave no sign of erythema and edema detected within 72?h on the shaved rabbit skin by the closed patch test investigated by mexameter and visual observation, respectively. These formulations also demonstrated higher hydration enhancement and improvement of skin lightening, thickness, roughness, and elasticity on the skin of 30 human volunteers within the 28–day treatment not more than 9, 27, 7, 3, and 3 times, respectively.

Discussion and conclusions: The formulations containing niosomes entrapped with the rice bran bioactive compounds gave superior clinical anti-aging activity which can be applied as a novel skin product.     

In vitro anti-aging activities of Terminalia chebula gall extract

Context: The Thai Lanna region has its own folklores and wisdoms in various fields such as traditional medicines. The galls of Terminalia chebula Retz. (Combretaceae) frequently appear in many Thai Lanna medicinal plant recipes for promoting longevity.

Objectives: To investigate the in vitro anti-aging activities of the extracts from 15 plants including T. chebula gall selected from the Thai medicinal plant recipes that have been traditionally used for longevity.

Materials and methods: The plant extracts were prepared by four extraction methods including hot (HW) and cold (CW) aqueous processes and hot (HM) and cold (CM) methanol processes. These extracts were tested for antioxidative and tyrosinase inhibition activity as well as the proliferative and MMP-2 inhibition activity on early aging human skin fibroblasts in order to evaluate their in vitro anti-aging activity.

Results: At 0.1?mg/mL, the CW extract of T. chebula gall exhibited the highest DPPH radical scavenging activity with scavenging of 84.64%?±?2.22%, whereas ascorbic acid, α-tocopherol and butylated hydroxyl toluene gave 96.50%?±?0.1%, 35.74%?±?0.2% and 27.43%?±?0.1%, respectively. The CW extract of T. chebula gall indicated the highest stimulation index (SI) on normal human fibroblast proliferation of 1.441 which was more active than ascorbic acid (SI 1.21). This extract has also demonstrated MMP-2 inhibition on fibroblasts determined by zymography 1.37 times more potent than ascorbic acid.

Discussion and conclusion: This study has confirmed the traditional use of T. chebula gall in many Thai medicinal plant recipes for longevity which will be beneficial for further development of anti-aging products.     

Collagen loaded nano-sized surfactant based dispersion for topical application: formulation development,characterization and safety study

Abstract

Collagen, a high molecular weight, hydrophilic and highly abundant protein is known to have anti-ageing, anti-wrinkle, anti-acne, anti-scar and wound healing properties. High molecular weight and hydrophilic nature hinder its effective topical delivery. So, the objective of present study was to develop effective topical nano-surfactant dispersion (NSD) for collagen delivery. NSD was prepared from sorbitan monostearate (Span60) and cholesterol using ethanol injection method followed by probe sonication. NSD was characterized for entrapment efficiency (%EE), size and size distribution (Z-avg and polydispersity index (PDI)), shape, zeta-potential (ζ), in vitro drug release, skin hydration and skin irritation test and histopathological examination. Optimized NSD (NSD3) had %EE, z-avg, PDI and ζ-potential of 77.56%?±?1.09%, 158.1?±?2.31?nm, 0.211 and ?17.2?±?0.64?mV, respectively. In in vivo skin hydration test, NSD treatment showed nearly 2.5-fold and 3-fold increase in the thickness of stratum corneum (SC) as compared to the collagen gel treated and untreated skin, respectively. The mean scores of skin irritation test in two animal species, rats and rabbits, were found to be 1.42?±?1.01 and 1.71?±?0.29, respectively, indicating the non-irritant nature of collagen loaded NSD. Histopathology of the skin after application of developed NSD showed non-significant changes in skin anatomy indicating its safe nature.     

Anti-inflammatory activity of gel containing novel elastic niosomes entrapped with diclofenac diethylammonium

The objective of this study was to develop a novel elastic bilayer vesicle entrapped with the non-steroidal anti-inflammatory drug (NSAID), diclofenac diethylammonium (DCFD) for topical use. Eighteen bilayer vesicular formulations composing of DPPC or Tween 61 or Span 60 mixed with cholesterol (at 1:1, 3:7 and 1:1 molar ratios, respectively) and ethanol at 0-25% (v/v), by chloroform film method with sonication were developed. The elastic Tween 61 niosomes which gave no sedimentation, no layer separation, unchanged particle sizes (about 200 nm) were selected to entrap DCFD. The entrapment efficiency of the drug in the conventional and elastic Tween 61 niosomes was 65 and 93%, respectively. At least 87% of DCFD determined by HPLC remained in elastic Tween 61 niosomes when kept at 4, 27 and 45 degrees C for 3 months. The deformability index values of the elastic niosomes were 13.76 and 3.44 times higher than the conventional niosomes entrapped and not entrapped with the drug, respectively, indicating the higher flexibility of the elastic vesicle especially, when entrapped with the drug. Transdermal absorption through excised rat skin was performed by vertical Franz diffusion cell at 32+/-2 degrees C for 6h. Gel containing elastic niosomes exhibited fluxes of DCFD in the stratum corneum (SC), deeper skin layer (viable epidermis and dermis, VED) and receiver chamber at 191.27+/-9.52, 16.97+/-2.77 and 3.76+/-0.54 microg/(cm2 h), whereas the commercial emulgel, containing an equivalent DCFD, gave 60.84+/-13.63, 7.33+/-1.70 and 0.14+/-0.01 microg/(cm2 h), respectively. The in vivo anti-inflammatory activity was evaluated by ethyl phenylpropiolate (EPP)-induced rat ear edema (n=3). DCFD entrapped in the developed elastic niosomes and incorporated in gel gave the same ear edema inhibition percentages of 23.81% at 30 min, but 2 and 9 times more inhibition percentages at 45 and 60 min than the commercial emulgel, respectively. This result has not only demonstrated the enhancement of transdermal absorption through rat skin, but also the in vivo anti-inflammatory effect of DCFD when entrapped in the developed novel elastic Tween 61 niosomes, as well.     

Ethanol extract of Terminalia chebula fruit protects against UVB-induced skin damage

Context: The fruit of Terminalia chebula Retz. (Combretaceae) has been used for several therapeutic purposes in Thai folk medicines. Currently, the ethanol extracts containing antioxidant compounds have shown the ability to promote collagen synthesis.

Objective: This purpose of this work was to study the effects of the ethanol extract from T. chebula fruit on the inhibition of cutaneous photodamage.

Materials and methods: The viability of human skin fibroblasts after incubation with T. chebula at concentration 0.5–50?μg/mL for 24, 48 and 72?h was assessed by using sodium 3′-[(phenyl-amino)-carbonyl]-3,4,tetrazolium-bis(4-methoxy-6-notro)benzene-sulphonic acid hydrate (XTT). The levels of type I procollagen and matrix metalloproteinases (MMP)-1 and MMP-13 produced by UVB-irradiated fibroblasts were determined by ELISA. Skin thickness and collagen content caused by long-term UVB irradiation in male ICR mice were determined from haematoxylin and eosin stained tissue sections and spectrophotometric measurement of hydroxyproline.

Results: The extract (0.5–50?μg/mL) had no effect on cell viability or morphology of the human fibroblasts. In vitro studies showed that the T. chebula extract reduced the UVB-induced MMP-1 and MMP-13 expression, whereas an increased production of type I procollagen was observed. In a UVB-irradiated animal model, male ICR mice with hair shaved were chronically exposed to UVB which lead to epidermal thickness and loss of hydroxyproline. However, these effects were fully prevented by the topical application of the T. chebula ethanol extract.

Discussion and conclusion: These data suggested that the T. chebula ethanol fruit extract is an efficacious pharmaceutical protectant of skin against photodamage.     

Skin penetration and photoprotection of topical formulations containing benzophenone-3 solid lipid microparticles prepared by the solvent-free spray-congealing technique

Abstract

Purpose: Solid-lipid microparticles loaded with high amounts of the sunscreen UV filter benzophenone-3 were prepared by spray congealing with the objective of decreasing its skin penetration and evaluate whether the sunscreen’s photoprotection were impaired by the microencapsulation process. Methods: The microparticles were produced using the natural lipids carnauba wax or bees wax and three different concentrations of benzophenone-3 (30, 50 and 70%) using spray congealing technique. Results: The microparticles presented properties suitable for topical application, such as spherical morphology, high encapsulation efficiency (95.53–102.2%), average particle sizes between 28.5 and 60.0?µm with polydispersivities from 1.2 to 2.5. In studies of in vitro skin penetration and preliminary stability, formulations of gel cream containing carnauba wax solid lipid microparticles and 70% benzophenone-3 when compared to the formulation added of bees wax solid-lipid microparticles containing 70% benzophenone-3, was stable considering the several parameters evaluated and were able to decrease the penetration of the UV filter into pig skin. Moreover, the formulations containing solid lipid microparticles with 70% benzophenone-3 increased the photoprotective capacity of benzophenone-3 under UV irradiation. Conclusion: The results show that spray-congealed microparticles are interesting solid forms to decrease the penetration solar filters in the skin without compromising their photoprotection.     

Solid lipid nanoparticles-loaded topical gel containing combination drugs: an approach to offset psoriasis

Aim: The primary aim of present work was to develop effective combination drug therapy for topical treatment of psoriasis.

Methods: Betamethasone dipropionate and calcipotriol loaded solid lipid nanoparticles (CT-BD-SLNs) were prepared by hot melt high shear homogenization technique, which were then incorporated in Carbopol gel matrix. The anti-psoriatic potential was tested by sequential in vitro (skin permeation and dermal distribution, anti-proliferative effect in HaCaT cells) and in vivo (Draize patch irritation, transepidermal water loss (TEWL) and anti-psoriatic mouse tail studies) experiments.

Results: A negligible amount in receptor compartment, yet confined distribution of drugs to epidermal and dermal region of skin was observed in case of SLNs, which is essential for safe and effective anti-psoriatic therapy. Draize patch test and TEWL demonstrated negligible skin irritation and better skin tolerability of SLNs. The in vitro HaCaT cell line study demonstrated that SLNs delayed the abrupt growth of keratinocytes, while in vivo mouse tail model showed that SLNs gel significantly decreased the epidermal thickness and increased melanocyte count in comparison to commercial Daivobet® ointment.

Conclusions: The developed SLNs gel is expected to be potential strategies for treatment of psoriasis and other topical diseases.     

Enhancement of gene expression and melanin production of human tyrosinase gene loaded in elastic cationic niosomes

Objectives Disturbance in the synthesis of tyrosinase might be one of the major causes of vitiligo. The enhancement of tyrosinase gene expression and melanin production by loading the plasmid in elastic cationic niosomes was investigated in tyrosinase gene knocked out human melanoma (M5) cells and in tyrosine‐producing mouse melanoma (B₁₆F₁₀) cells. Methods Niosomes composed of Tween 61/cholesterol/dimethyl dioctadecyl ammonium bromide at 1 : 1 : 0.5 molar ratio were prepared by the freeze‐dried empty liposomes method. The thin lipid film was redissolved in distilled water or 25% ethanol to obtain the non‐elastic or elastic cationic niosomes, respectively. Key findings The maximum loading of the plasmid in non‐elastic and elastic niosomes was 130 and 100 µg per 16 mg of the niosomal contents, respectively. The plasmid‐loaded elastic cationic niosomes exhibited high specific tyrosinase activity of 1.66 and 1.50 fold in M5 cells and 6.81 and 4.37 fold in B₁₆F₁₀ cells compared with the free plasmid and the plasmid‐loaded non‐elastic cationic niosomes, respectively. Conclusions This study has demonstrated not only the enhancement of the expression of human tyrosinase gene by loading in elastic cationic niosomes, but also the potential application of this gene delivery system for the further development of vitiligo gene therapy.     

Employing photoacoustic spectroscopy in the evaluation of the skin permeation profile of emulsion containing antioxidant phenolic-rich extract of Melochia arenosa

Context: Oxidative stress is an important factor modulating skin alterations. Melochia arenosa Benth. (Malvaceae) is a Brazilian plant with antimicrobial activity and antioxidant potential.

Objective: The objective of this study is to develop a topical formulation containing antioxidant phenolic-rich extract of M. arenosa and to evaluate its skin permeation profile.

Materials and methods: Response surface methodology was used to maximize the total phenolic (TP) content of the extract and its antioxidant activity was evaluated by 2,2-diphenyl-1-picryl-hydrazyl (DPPH), 2,2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and respiratory burst methods. An emulsion containing 1% optimized extract (OE) was developed and employed photoacoustic spectroscopy (PAS) for the determination of its skin permeation profile. The morphology of the skin was studied in histological sections stained with hematoxylin–eosin.

Results and discussion: The optimum conditions predicted for the major extractive efficiency of the phenolics with 100% ethanol led extraction time 101?h and plant:solvent proportion 1:13.5 (w/v). OE presented TP?=?724.6?±?8.2?mg GAE/g extract and scavenging capacity of DPPH (IC₅₀ value?=?11.43?±?0.14?µg/mL) and ABTS radicals (IC₅₀ value?=?35.42?±?0.48?µg/mL). The production of ROS by neutrophils after stimulation with phorbol miristate acetate was lower when the OE was present in the reaction medium, endorsing its high antioxidant capacity. The data obtained by PAS indicated that the OE present in the emulsion has permeated and was distributed in the whole skin. No histopathological alterations were observed in the histological analysis.

Conclusion: The formulation developed is a promising tool for skin care and could prevent the damage caused by oxidative stress.     

Microsponges enriched gel for enhanced topical delivery of 5-fluorouracil

Abstract

This study aimed to develop microsponges based topical gel formulation of 5-Fluorouracil (5-FU) for the treatment of skin cancer with enhanced skin deposition and reduced skin irritation potential. Microsponges were prepared by Quasi-emulsion solvent diffusion method using ethyl cellulose and Eudragit RL 30?D; and was optimised through detailed in vitro characterisation. Brunauer–Emmett–Teller (BET) analysis demonstrated higher surface area (2.4393?m²/g) and pore volume of developed microsponges formulation. Optimised formulation showed better thixotropic and texture properties compared to commercial cream formulation, used as control for comparison purpose. Further, the optimised formulation demonstrated 5.5-fold increase in skin deposition documented via in-vivo local bioavailability study, with significant reduction in skin irritation compared to the commercial formulation. Hence, the developed microsponges based formulation seems to be a viable alternative with enhanced topical delivery of 5-FU as compared to the commercial formulation.     

Anti-inflammatory,anti-lipid peroxidative,antioxidant and membrane stabilizing activities of hydroalcoholic extract of Terminalia chebula fruits

Abstract

Context: Arthritis is inflammation of one or more joints. Terminalia chebula Retz. (Combretaceae) fruit is mentioned in Ayurveda as useful in treating arthritic disorders.

Objective: This work was undertaken to evaluate the anti-inflammatory, antioxidant, anti-lipid peroxidative and membrane-stabilizing effects of hydroalcoholic extract of Terminalia chebula fruits and also to establish a possible association between them.

Materials and methods: In vivo anti-inflammatory activity of T. chebula fruit extract at different doses ranged from 50 to 500?mg/kg, p.o. was evaluated against carrageenin-induced inflammation in rats. Human erythrocyte hemolytic assay was used for in vitro anti-inflammatory activity testing with 50 to 500?µg/ml fruit extract. Antioxidant potential of test fruit extract (10 to 100?µg/ml) was evaluated using TBARS and DPPH methods. The fruit extract was standardized for total phenolic content using Folin-Ciocalteu method.

Results: The standardized extract at 250?mg/kg, p.o. dose caused 69.96% reduction in carrageenin-induced rat paw edema and demonstrated 96.72% protective effect on human RBC membrane stability. Besides, T. chebula fruit extract significantly reduced the in vivo formation of TBARS in carrageenin-induced rat liver with IC₅₀ 94.96?mg/kg, p.o. and also in vitro radical scavenging activities in DPPH assay method with IC₅₀ 42.14?µg/ml. The standardized extract contains phenolics 118.5?mg gallic acid equivalent/g of extract.

Discussion and conclusion: These promising findings support the traditional use of T. chebula fruits in the treatment of arthritic disorders and suggest that radical quenching may be one of the mechanisms for its anti-inflammatory activity.     

Formulation and characterization of Phospholipon 90 G and tween 80 based transfersomes for transdermal delivery of eprosartan mesylate

The objective of the current study was to formulate the eprosartan mesylate loaded transfersomes using different proportions of Phospholipon^® 90?G and Tween^® 80 (95–75:5–25% w/w). The prepared transfersomes were characterized for their vesicles size, shape, polydispersity index, zeta potential, entrapment efficiency, in vitro skin permeation, confocal laser scanning microscopy, and in vivo skin irritation. Results revealed that the formulated transfersomes were negatively charged, spherical unilamellar structure of 71.18–85.66?nm with entrapment efficiency of 83.00–88.19%, and presented transdermal flux of 1.78–5.02?μg/cm²/h across rat skin. Confocal laser scanning microscopy confirmed that the formulated rhodamine 6?G loaded transfersomes could penetrate deeply and uniformly into rat skin. Additionally, in vivo skin irritation studies revealed that the prepared transfersomes were devoid of any skin irritation potential (erythema and edema). Results of this study revealed that the transfersomes prepared with Tween^® 80 could be used to enhance the transdermal delivery of eprosartan mesylate. In conclusion, transdermal transfersomes formulation may prove to be an encouraging drug carrier for eprosartan mesylate and other actives, particularly owing to their simple formulation and unsophisticated scale-up methods.     

Short term study of human skin irritation by single application closed patch test: assessment of four multiple emulsion formulations loaded with botanical extracts

Background: Assessment of skin irritation potential is a major concern in safety assessment of cosmetics, when long-term use of these products are expected. Non-invasive bioengineering probes have been used previously to measure skin irritation potential of cosmetic ingredients.

Objectives: Experimentation carried out to weigh up the skin irritation potential of four multiple emulsion formulations via visual and non-invasive measurements. Immediate effects of formulations and comparison of two assessment techniques were also tried to establish.

Methods: Four multiple emulsion formulations one control (without botanical active) and three containing the functional botanical actives plus additives were tested in this study using the following techniques: transepidermal water loss (TEWL), COLIPA visual scoring method (CVSM), Mexameter MPA 5 (Courage + Khazaka, Germany) and capacitance [Corneometer MPA 5 (Courage + Khazaka, Germany)]. Visual examination and non-invasive measurements were performed at baseline and after 24?h. The formulations were applied on the forearm of 12 healthy volunteers of same sexes aged 20–25 years.

Results: We found that none of the formulation produced irritation both on visual and instrumental evaluation. However, formulations MeB and MeC have comparable immediate effects on dryness, erythema, melanin and TEWL. Formulation MeC produced more effective results on different parameters, may be due to synergistic effect of two extracts, while MeA failed to produce any immediate effects on skin parameters. Moreover results of both assessment methods are parallel to each other.

Conclusions: None of the formulation produce irritant effects, barrier impairment effects or immediate effects except for the formulation MeC which produced appreciable results than other formulations but statistically these results were insignificant (p?>?0.05). Based on these results, it could be concluded that formulations may be implied safely as skin rejuvenating candidates.     

Percutaneous delivery of α-melanocyte-stimulating hormone for the treatment of imiquimod-induced psoriasis

Purpose: α-Melanocyte-stimulating hormone (α-MSH) is an endogenous peptide hormone with anti-inflammatory responses. We developed topical formulation(s) of α-MSH to reduce psoriasis-related inflammation.

Methods: Transcutol (TC) and n-methyl 2-pyrrolidone (NMP) were used to formulate a gel for α-MSH. Skin permeation and dermal microdialysis of the solution and optimized gel were performed. The inflammatory response of α-MSH gel was investigated in imiquimod-induced psoriasis mouse model. Histology and immunohistochemistry were then performed on treated skin.

Results: Solution comprising 50%w/w TC and 10%w/w NMP showed higher (p?<?0.05) skin retention (0.27?±?0.024?µg of α-MSH/mg of skin) than solutions containing either 50% w/w TC or 10% w/w NMP at 24?h. Dispersion of α-MSH in Carbopol Ultrez 10 produced a uniform dispersion. α-MSH gel showed pseudoplastic flow with thixotropic behavior. Dermal microdialysis results suggested that skin permeation of gel after 5?h was 1.9-folds higher than the solution. Further, gel-treated psoriatic-like plaque skin sections showed significant (p?<?0.05) decrease in the expression of a melanocortin receptor, in the psoriasis area and severity index score and transepidermal water loss compared to the solution.

Conclusion: TC, NMP and Carbopol Ultrez 10 form a stable gel with improved skin permeation of α-MSH for a reduction in psoriasis-associated inflammation.     

Nanoemulsion gel-based topical delivery of an antifungal drug: in vitro activity and in vivo evaluation

Abstract

Objective: In this study, attempt has been focused to prepare a nanoemulsion (NE) gel for topical delivery of amphotericin B (AmB) for enhanced as well as sustained skin permeation, in vitro antifungal activity and in vivo toxicity assessment.

Materials and methods: A series of NE were prepared using sefsol-218 oil, Tween 80 and Transcutol-P by slow spontaneous titration method. Carbopol gel (0.5%?w/w) was prepared containing 0.1%?w/w AmB. Furthermore, NE gel (AmB-NE gel) was characterized for size, charge, pH, rheological behavior, drug release profile, skin permeability, hemolytic studies and ex vivo rat skin interaction with rat skin using differential scanning calorimeter. The drug permeability and skin irritation ability were examined with confocal laser scanning microscopy and Draize test, respectively. The in vitro antifungal activity was investigated against three fungal strains using the well agar diffusion method. Histopathological assessment was performed in rats to investigate their toxicological potential.

Results and discussion: The AmB-NE gel (18.09?±?0.6?µg/cm²/h) and NE (15.74?±?0.4?µg/cm²/h) demonstrated the highest skin percutaneous permeation flux rate as compared to drug solution (4.59?±?0.01?µg/cm²/h) suggesting better alternative to painful and nephrotoxic intravenous administration. Hemolytic and histopathological results revealed safe delivery of the drug. Based on combined results, NE and AmB-NE gel could be considered as an efficient, stable and safe carrier for enhanced and sustained topical delivery for AmB in local skin fungal infection.

Conclusion: Topical delivery of AmB is suitable delivery system in NE gel carrier for skin fungal infection.     

Formulation and evaluation of meloxicam niosomes as vesicular carriers for enhanced skin delivery

Context: Skin delivery of Meloxicam (MX) offers several advantages over the oral route which is associated with potential side effects.

Objectives: The aim of this study was to develop transdermal MX in niosomes.Materials and Methods: Vesicles prepared by thin film hydration method were characterized and the acute anti-inflammatory activity of 0.5% MX niosomal hydrogel was evaluated using carrageenan induced rat paw edema method. Results: The results revealed that niosomes prepared from span 60 and cholesterol at 6:4 molar ratio using 20?mg of MX were of the highest entrapment efficiency (> 55%) and with particle size (187.3?nm). There was a marked increase in the percentage inhibition of edema in animals treated with MX vesicular gel compared to those treated with free MX and piroxicam gels.

Discussion: There was an inverse proportionality between vesicle size and cholesterol content. With increased cholesterol molar ratio the bilayer stability increased and permeability decreased leading to efficiently trapping the MX. In contrast, higher amounts of cholesterol may compete with the drug for packing space within the bilayer. The inhibitory effect of MX niosomal gel may be attributed to its superior skin permeation.

Conclusions: The results suggest that niosomes may be promising vehicles for transdermal delivery of MX.     

Curcumin entrapped hyaluronan containing niosomes: preparation,characterisation and in vitro/in vivo evaluation

Curcumin, a natural polyphenolic compound, has numerous pharmacological activities; while it faces several bioavailability problems, due to its poor solubility and stability. So, many nanostructures have been designed to overcome these drawbacks. The aim of this study was to prepare a polymeric niosomal structure by incorporating hyaluronan to improve curcumin efficiencies. Hyaluronan containing niosomes were prepared by thin film hydration medium with slight modifications. In the formulation of hyaluronan containing niosomes size and zeta potential studies, Atomic Force Microscopy (AFM), Transmission Electron Microscopy (TEM), Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC), X-Ray Diffraction (XRD), in-vitro release test, DPPH antioxidant assay and in-vivo anti-inflammatory test were investigated. The results showed that hyaluronan containing niosomes were 249.83?±?6.38?nm and the entrapment of curcumin was 98.28?±?0.278% (w/w). In addition, the shape of the hyaluronan containing niosomes was spherical. 500?µl of the prepared formulation with 4.002?×?10^?7 moles of curcumin showed 100% antioxidant effect. Moreover, the anti-inflammatory effect of the hyaluronan containing niosomes was higher than the anti-inflammatory effect of the simple suspension of curcumin.     

Localized delivery of a lipophilic proteasome inhibitor into human skin for treatment of psoriasis

Purpose: Pentaerythritol tetrakis (3,5-di-tert-butyl-4-hydroxyhydrocinnamate) (PTTC) is a cinnamate tetraester with proteasome inhibitor activity, which may be used as a topical treatment in psoriasis, but has a computed log?P of 23. The objective of this in vitro study was to determine the intradermal delivery, skin irritation and potential efficacy of PTTC in treating psoriasis.

Methods: Solubility studies were performed to find a suitable vehicle for PTTC. Permeation studies were performed with microneedle-treated skin. A cell culture irritation test was dosed with a positive control, negative control and PTTC. An MTT assay was performed to evaluate cell viability and irritancy. Psoriatic cell culture was also dosed with PTTC and IL-6 levels were determined by ELISA.

Results: Solubility was greatest in dimethyl sulfoxide and ethyl pyruvate, with dimethyl sulfoxide delivering a greater amount (2343.41?±?384.26?µg) into stratum corneum. PTTC alone as well as topical PTTC emulsion formulation were found to be non-irritant with cell viability of 69.0?±?5.64% and 74.6?±?5.03%, respectively. Treatment with neat PTTC slightly reduced IL-6 levels and PTTC emulsion significantly reduced IL-6 levels to 92.53?±?12.74?pg/ml compared to basal levels (141.69?±?8.41?pg/ml).

Conclusion: PTTC can be delivered intradermally to potentially treat psoriasis.     

Enhancement of Transdermal Absorption,Gene Expression and Stability of Tyrosinase Plasmid (pMEL34)-Loaded Elastic Cationic Niosomes: Potential Application in Vitiligo Treatment

The pMEL34 was loaded in elastic cationic niosomes (Tween61/Cholesterol/DDAB at 1:1:0.5 molar ratio) by chloroform film method with sonication and rehydrated with 25% ethanol. The amount of pMEL34 was determined by gel electrophoresis and gel documentation. The maximum loading of pMEL34 in elastic cationic niosomes was 150 mg/16 mg of the niosomal compositions. At 8 weeks, the remaining plasmid in the elastic niosomes kept at 4 ± 2 °C, 27 ± 2 °C were 49.75% and 38.57%, respectively, whereas at 45 ± 2 °C, all plasmids were degraded. For transdermal absorption through rat skin investigated by Franz diffusion cells at 6 h, the fluxes of pMEL34 loaded in elastic and nonelastic niosomes in viable epidermis and dermis (VED) were 0.022 ± 0.00 and 0.017 ± 0.01 μg/cm²/h, respectively, whereas only pMEL34 loaded in elastic cationic noisome was observed in the receiver solution. The pMEL34 loaded in elastic cationic niosomes showed the highest tyrosinase gene expression demonstrating higher tyrosinase activity than the free and the loaded plasmid in nonelastic niosomes of about four times. This study has suggested the potential application of elastic cationic niosomes as an efficient topical delivery for tyrosinase gene in vitiligo therapy. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:3533-3541, 2010