Nano-lipoidal carriers of tretinoin with enhanced percutaneous absorption,photostability, biocompatibility and anti-psoriatic activity

Tretinoin (TRE) is a widely used retinoid for the topical treatment of acne, psoriasis, skin cancer and photoaging. Despite unmatchable efficacy, it is associated with several vexatious side effects like marked skin erythema, peeling and irritation, eventually leading to poor patient compliance. Its photo-instability and high lipophilicity also pose challenges in the development of a suitable topical product. The present study, therefore, aims to develop biocompatible lipid-based nanocarriers of TRE to improve its skin delivery, photostability, biocompatibility and pharmacodynamic efficacy. The TRE-loaded liposomes, ethosomes, solid lipid nanoparticles (SLNs) and nanostructured lipidic carriers (NLCs) were prepared and characterized for micromeritics, surface charge, percent drug efficiency and morphology. Bioadhesive hydrogels of the developed systems were also evaluated for rheological characterization, photostability, ex vivo skin permeation and retention employing porcine skin, and anti-psoriatic activity in mouse tail model. Nanoparticulate carriers (SLNs, NLCs) offered enhanced photostability, skin transport and anti-psoriatic activity vis-à-vis the vesicular carriers (liposomes, ethosomes) and the marketed product. However, all the developed nanocarriers were found to be more biocompatible and effective than the marketed product. These encouraging findings can guide in proper selection of topical carriers among diversity of such available carriers systems.     

Effective topical delivery systems for corticosteroids: dermatological and histological evaluations

Abstract

Atopic dermatitis (AD) is a chronic and relapsing skin disease with severe eczematous lesions. Long-term topical corticosteroid treatment can induce skin atrophy, hypopigmentation and transepidermal water loss (TEWL) increase. A new treatment approach was needed to reduce the risk by dermal targeting. For this purpose, Betamethasone valerate (BMV)/Diflucortolone valerate (DFV)-loaded liposomes (220–350?nm) were prepared and incorporated into chitosan gel to obtain adequate viscosity (～13?000 cps). Drugs were localized in stratum corneum?+?epidermis of rat skin in ex-vivo permeation studies. The toxicity was assessed on human fibroblast cells. In point of in-vivo studies, pharmacodynamic responses, treatment efficacy and skin irritation were evaluated and compared with previously prepared nanoparticles. Liposome/nanoparticle in gel formulations produced higher paw edema inhibition in rats with respect to the commercial cream. Similar skin blanching effect with commercial creams was obtained via liposome in gels although they contain 10 times less drug. Dermatological scoring results, prognostic histological parameters and suppression of mast cell numbers showed higher treatment efficiency of liposome/nanoparticle in gel formulations in AD-induced rats. TEWL and erythema measurements confirmed these results. Overview of obtained results showed that liposomes might be an effective and safe carrier for corticosteroids in skin disease treatment.     

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.     

Microemulsions mediated effective delivery of methotrexate hydrogel: more than a tour de force in psoriasis therapeutics

Methotrexate (MTX), a well known drug for the treatment of cancer and rheumatoid arthritis, has gained prominence in the treatment of psoriasis over the period of years. However, the present mode of systemic administration through oral or parenteral route has always proposition, full of compromises. The toxicity of drug to the vital organs and physiological environment is the major concern. Also, its poor skin penetration is one major problem. Hence novel system based on lipid carriers has been considered here to overcome the barriers. Microemulsions (MEs) were prepared using pseudo-ternary phase diagram (PTPD) and they were characterized for various parameters such as size, shape (cryo-SEM), PDI, zeta potential, etc. The chosen MEs system (optimized) was then incorporated into secondary vehicles and characterized for rheological behavior, texture profile analysis, in vitro release, ex vivo permeation and drug distribution into different layers of skin. The developed formulations were further evaluated in ex vivo and in vivo such as cell line study, imiquimod-induced psoriatic model, allergic contact dermatitis, rat tail model (% orthokeratosis) and safety test (Draize test). The MEs based MTX gel has shown its potential in locating the drug at the desired domain of stratum corneum, epidermal and dermal layers of skin and reducing systemic absorption. Our results are suggestive of MEs potential as a novel carrier for topical delivery of MTX in topical therapeutic and safety approaches. In conclusion, developed MEs-based hydrogel has shown promising results in achieving effective delivery of MTX.     

Hyperbranched dendritic nano-carriers for topical delivery of dithranol

Abstract

The purpose of the current investigation was to explore the potential of polypropylene imine (PPI) dendrimers to deliver dithranol (DIT) topically and to evaluate its encapsulation, permeation and skin irritation potential. PPI (5.0 generation, 5.0?G) dendrimers and DIT-loaded PPI (DIT–PPI) were prepared and characterized by spectroscopy and transmission electron microscopy. DIT encapsulation, in vitro skin permeation study, skin irritation studies, fluorescent studies and tape stripping studies were performed. Loading of DIT was found to be pH dependent with maximum encapsulation at acidic pH (1.0?±?0.02, 17.2?±?0.56 and 57.1?±?1.32% at 7.4, 5.5 and 1.2 pH, respectively). DIT–PPI showed significantly enhanced permeation rate constant and lesser skin irritation (11.61?±?1.80?μg/cm²/h and 1.0, respectively) when compared with the plain DIT solution (2.72?±?0.31?μg/cm²/h and 2.3, respectively). Skin separation studies and confocal laser scanning microscope images showed that the dye-loaded dendrimers exhibits deposition of dye in pilosebaceous compartment. These studies demonstrate that PPI can be exploited to improve the topical bioavailability of the molecules in a controlled pattern. The enhanced accumulation of DIT via dendrimer carrier within the skin might help optimize targeting of this drug to the epidermal and dermal sites, thus creating new opportunities for well-controlled, modern topical application of DIT for the treatment of psoriasis.     

Utility of MTT assay in three-dimensional cultured human skin model as an alternative for draize skin irritation test: approach using diffusion law of irritant in skin and toxicokinetics-toxicodynamics correlation

Purpose. A cytotoxicity assay using a three-dimensional cultured human skin model, Living Skin Equivalent-high (LSE-high) was evaluated as an alternative to the Draize skin irritation tests using animals. A relation between the cytotoxicity and calculated concentration of an irritant in skin was also evaluated. Methods. Colorimetric thiazoyl blue (MTT) conversion assay and a surfactant, cetylpyridinium chloride (CPC), were selected as a cytotoxicity assay and a model irritant. The fraction of dead cell number in the MTT assay or the Draize irritation score (in vitro and in vivo irritation data, respectively) was treated as a function of CPC concentration in the viable skin of LSE-high and guinea pig. Separately, in vitro permeations of CPC through the LSE-high or excised guinea pig skin were determined to calculate the average concentration of CPC in the viable skin using the Fickian diffusion theory. The obtained relations between the irritation scores and CPC concentration were evaluated by the Emax model (Hill equation). Results. CPC concentration showing 50% irritation (IC ₅₀) was similar for the MTT assay (18.9%) and Draize test (12.3%), and a good relationship (r = 0.981) was observed between the fraction of dead cell number and the Draize score. In contrast, IC ₅₀, 1.32%, for the MTT assay in LSE-high was much lower than that using guinea pig skin. We then corrected the results for the MTT assay using a ratio of IC ₅₀ in guinea pig skin against LSE-high, resulting in a good relation between both MTT results in guinea pig skin and LSE-high. Conclusion. The present results suggest that the MTT assay using LSE-high may be utilized as an alternative for the Draize test in animals for evaluating skin irritation.     

Topical delivery for the treatment of psoriasis

Importance of the field: Psoriasis is one of the most common human skin diseases. Topical therapy forms the cornerstone in the management of mild-to-moderate psoriasis. Topical therapies are also used as adjunctive to systemic therapy in moderate and severe forms of the disease.

Areas covered in this review: In this review, an overview of psoriasis pathogenesis, new topical medications for psoriasis, new targets and molecules, combination topical therapies and combination of topical and phototherapy is provided. Over the past decade several efficacious and acceptable treatment options have emerged from the age-old therapies. The development of sophisticated formulation options has led to an enhancement in the rate and extent of drug delivery across the skin, increasing therapeutic value and improving patient compliance.

What the reader will gain: Readers will learn about monotherapy and combination topical products as well as new topical drug delivery technology to achieve optimal clinical outcomes. This review will highlight the need to generate more dermal pharmacokinetic data for better understanding of the impact of formulation change on skin pharmacokinetics to help design improved topical drug delivery systems.

Take home message: New topical formulations have the potential to achieve better efficacy with improved safety profile.     

Assessment of dermal toxicity of nanosilica using cultured keratinocytes,a human skin equivalent model and an in vivo model

Assessments of skin irritation potentials are important aspects of the development of nanotechnology. Nanosilica is currently being widely used for commercial purposes, but little literature is available on its skin toxicity and irritation potential. This study was designed to determine whether nanosilica has the potential to cause acute cutaneous toxicity, using cultured HaCaT keratinocytes (CHK), a human skin equivalent model (HSEM), and in vivo model. Nanosilica was characterized by scanning electron microscopy. We evaluated the cytotoxic effects of nanosilica on CHKs and the HSEM. In addition, we also investigated whether two commercially available nanosilicas with different sizes (7 and 10–20 nm) have different effects. To confirm in vitro results, we evaluated the irritation potentials of nanosilicas on rabbit skin. Nanosilicas reduced the cell viabilities of CHKs in a dose-dependent manner. However, the HSEM revealed no irritation at 500 μg/ml of nanosilica. Furthermore, this result concurred with Draize skin irritation test findings. The present study data indicate that nanosilica does not cause acute cutaneous irritation. Furthermore, this study shows that the HSEM used provides more useful screening data than the conventional cell culture model on the relative toxicities of NPs.     

Assessment of dermal irritation potential of MWCNT

There is an increasing concern regarding the potential toxicity of nanoparticles (NPs), but little literature is available on its skin toxicity and irritation potential. We investigated whether multi-walled carbon nanotubes (MWCNTs) affect skin irritation using HaCaT cell line, the human skin equivalent model (HSEM), and anin vivo model. We evaluated the cytotoxic effects of MWCNTs on HaCaT cells and the HSEM. To confirm in vitro results, we evaluated the irritation potentials of MWCNTs on rabbit skin. In MTT assay, MWCNTs cytotoxicity depended on the concentration of MWCNTs in HaCaT cells. The HSEM skin irriation experiments revealed that MWCNTs have no irritation potential. These HSEM data are consistent with Draize skin irritation test. MWCNTs did not induce the cutaneous irritation of rabbit skin. We suggest that MWCNTs do not induce any acute cutaneous irritation and the HSEM offers a useful alternative method for evaluating the toxicities of toxicants including NPs.     

Dermal toxicity and microscopic alterations by JP-8 jet fuel components in vivo in rabbit

In this study, we investigated the skin irritation, macroscopic and microscopic barrier alteration in vivo in rabbits from aliphatic and aromatic components of jet propellant-8 (JP-8) jet fuel. Macroscopic barrier properties were evaluated by measuring transepidermal water loss (TEWL), skin capacitance, and skin temperature; microscopic changes were observed by light microscopy. Draize visual scoring system was used to measure skin irritation. We found significant (P<0.05) increase in temperature at the site of all chemically saturated patches immediately after patch removal in comparison to the control site. Tridecane (TRI) produced a greater increase in temperature and capacitance at all time points than all the other components of JP-8. Both the aliphatic and aromatic components increased the TEWL at all time points. Tridecane produced greater increase in TEWL followed by naphthalene (NAP), 1-methylnaphthalene (1-MN), 2-metylnaphthalene (2-MN), tetradecane (TET), and dodecane (DOD). All of the above components of JP-8 caused moderate to severe erythema and edema, which were not resolved to the baseline even after 24 h of patch removal. Light microscopy revealed an increase in epidermal thickness (ET), and decrease in length and thickness of collagen fibers’ bundle by the above components of JP-8. These results suggest potential dermatotoxicity from the JP-8 components.     

In vitro and in vivo skin anti-aging evaluation of gel containing niosomes loaded with a semi-purified fraction containing gallic acid from Terminalia chebula galls

Context: The galls of Terminalia chebula Retz. (Combretaceae) frequently appear in many Thai Lanna medicinal plant recipes for promotion of longevity.

Objective: The objective of this study was to evaluate the skin anti-aging of gel containing niosomes loaded with a semi-purified fraction containing gallic acid from T. chebula galls.

Method: The semi-purified fraction containing phenolic compounds including gallic acid isolated from T. chebula galls loaded in non-elastic or elastic niosomes, and its developed gel, were evaluated for rabbit skin irritation by the closed patch test and skin anti-aging in human volunteers by measuring skin elasticity and roughness.

Results: Gel containing the fraction unloaded (SS) or loaded in non-elastic (SN) or elastic (SE) niosomes and gallic acid loaded in non-elastic (GN) or elastic (GE) niosomes showed no skin irritation, whereas the unloaded gallic acid (GS) gave the irritation in rabbit’s skin by the closed patch test. The % parameter changes of skin elastic recovery and skin elastic extension when applied with SN and SE gels were +28.73 and +32.57; ?21.25 and ?22.63%, respectively. SN and SE gel also showed a significant decrease of the maximum and average roughness values with the parameter changes of ?29.43 and ?32.38; ?39.47 and ?35.28%, respectively.

Conclusion: The semi-purified fraction loaded in niosomes indicated not only higher chemical stability of gallic acid containing in the fraction, but also more in vivo anti-aging activities than the unloaded fraction when incorporated in gel.     

Solid lipid nanoparticles and nanostructured lipid carrier-based nanotherapeutics in treatment of psoriasis: a comparative study

Background: The present work focuses on the development of ultra-small solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) encapsulating cyclosporine and calcipotriol, further incorporated into gel, increasing their penetration through the skin.

Research design and methods: Developed SLN and NLC were characterized regarding particle size, zeta potential, %entrapment efficiency and dispersed into carbopol 934P-NF gel. Gel was further characterized for rheological behavior and spreadability. Ex vivo dermatokinetic by tape stripping method, in vitro efficacy on HaCaT cell lines and in vivo efficacy on imiquimod induced psoriatic model in mice were evaluated.

Results: Ultra-small (size<100 nm) particles were formed with high entrapment efficiency and spherical morphology. Ex vivo dermatokinetic studies revealed deeper and confined drug penetration of lipid formulation gel in epidermal layers as compared to free drug. In vitro study on HaCaT cell lines depicted higher uptake and high efficacy owing to decrease in cell viability for NLC. The anti-psoriatic efficacy in BALB/c mice (evaluated on basis of cytokine levels and skin morphology) highlighted potential of drug-loaded NLC significantly higher as compared to drug loaded SLN and marketed formulation Betagel.

Conclusions: The study demonstrated that NLC gel had higher efficacy in psoriatic management and hold promise for further exploration.     

Evaluation of a tiered in vitro testing strategy for assessing the ocular and dermal irritation/corrosion potential of pharmaceutical compounds for worker safety

Introduction: Irritation reactions are a frequently reported occupational illness. The potential adverse effects of pharmaceutical compounds (PCs) on eye and skin can now be assessed using validated in vitro methods.

Objectives: Our overall aim is to reduce animal testing by replacing the historically utilized in vivo test methods with validated in vitro test methods which accurately determine the ocular and dermal irritation/corrosion potential of PCs to inform worker safety within the pharmaceutical space. Bristol–Myers Squibb (BMS) and the Institute for In Vitro Sciences (IIVS) have therefore conceptualized and internally qualified a tiered in vitro testing strategy to inform occupational hazards regarding eye and skin irritation and corrosivity of PCs. For the small scale pre-qualification phase, we paired historical in vivo and newly generated in vitro data for 15 PCs to determine the predictive capacity of in vitro assays already validated for the eye and skin irritation/corrosion endpoints and accepted for certain regulatory submissions. During the post-qualification phase, a group of 24 PCs were subjected exclusively to the developed tiered testing strategy, which is based on three Organisation for Economic Co-operation and Development (OECD) in vitro methods.

Materials and methods: The qualified in vitro testing strategy utilizes the Corrositex^® assay for the corrosivity (OECD TG 435), the Bovine Corneal Opacity and Permeability (BCOP) assay for ocular irritation (OECD TG 437), and the EpiDerm? tissue model-based Skin Irritation Test (SIT) for dermal irritation (OECD TG 439). In the first step, the pH of each PC was determined. For compounds with pH extremes ≥11 or ≤2, the Corrositex^® assay was generally conducted first. For compound(s) that were incompatible with or were negative in the Corrositex^® assay or had pH values between 2 and 11, the BCOP assay and SIT were performed first.

Results: The results of the tiered testing strategy’s qualification phase demonstrated that the BCOP assay is sensitive enough to identify a wide range of eye irritation/corrosion potentials and its over-prediction rate was considered acceptable to inform occupational hazards and ensure the proper handling practices of PCs. The SIT correctly predicted the skin irritation potential of 14 out of the 15 PCs included in the qualification phase, only over-predicting one PC. In the post-qualification phase, four PCs out of four tested were predicted corrosive by the Corrositex^® assay and thus no further testing was needed or conducted. The rest of the PCs were evaluated in the BCOP assay (both neat and as a 20% dilution), with the higher response being used for hazard classification. Four PCs were determined to be severe eye irritants, 1 a moderate irritant, 8 were mild irritants, and 8 were non-irritants. The same set of PCs was evaluated using the SIT and were classified as non-irritants to skin. These results are consistent with the BMS historical in vivo results showing a very low number of PCs as skin irritants.

Conclusions: This tiered in vitro testing strategy, which replaces the use of animal studies, was found to be reasonably accurate in its predictive capacity when compared to historical in vivo results and represents a conservative and reliable platform that can be utilized for the prediction of ocular and dermal irritation/corrosion potential of PCs and for subsequent GHS classification and worker safety hazard communications.     

Nanogel for dermal application of the triterpenoids isolated from Ganoderma lucidum (GLT) for frostbite treatment

Abstract

Objective: The purpose of this study was to formulate stable Ganoderma lucidum (GLT) nanogels suitable for topical delivery with a view to improve the therapeutic effect for frostbite.

Methods: GLT nanosuspensions were formulated using the high-pressure homogenization technique and then suitably gelled for characterized. In order to confirm the advantages of GLT nanogel for dermal application, skin permeation studies in vitro and pharmacodynamic evaluation in vivo were studied and compared with GLT–carbopol gel.

Results: The particle size analysis and SEM studies revealed that GLT nanosuspensions were still stably kept their particle size after suitably gelled by carbopol preparation. The drug content, pH, and spreadability of the GLT nanogel was found to be 99.23?±?1.8%, 6.07?±?0.1, and 26.42 (g·cm)/s, which were within acceptable limits. In vitro permeation studies through rat skin indicated that the amount of GLT permeated through skin of GLT nanogel after 24?h was higher than GLT–carbopol gel, and GLT nanogel increased the accumulative amount of GLT in epidermis five times than GLT–carbopol gel. No oedema and erythema were observed after administration of GLT nanogel on the rabbits' skin. Pharmacodynamic study showed that GLT nanogel was more effective than GLT–carbopol gel in treatment of frostbite.

Conclusion: The GLT nanogel possess superior therapeutic effect for frostbite compared with the GLT–carbopol gel, which indicates that nanogels are eligible for the use as a suitable nanomedicine for dermal delivery of poorly soluble drugs such as GLT.     

In Vivo Percutaneous Absorption,Skin Barrier Perturbation,and Irritation from JP-8 Jet Fuel Components

Abstract

JP-8 jet fuel has been reported to cause systemic and dermal toxicities in animal models and humans. There is a great potential for human exposure to JP-8. In this study, we determined percutaneous absorption and dermal toxicity of three components of JP-8 (i.e., xylene, heptane, and hexadecane) in vivo in weanling pigs. In vivo percutaneous absorption results suggest a greater absorption of hexadecane (0.43%) than xylene (0.17%) or heptane (0.14%) of the applied dose after 30 min exposure. Transepidermal water loss (TEWL) provides a robust method for assessing damage to the stratum corneum. Heptane showed greater increase in TEWL than the other two chemicals. No significant (p<0.05) increase in temperature was observed at the chemically treated site than the control site. Heptane showed greater TEWL values and erythema score than other two chemicals (xylene and hexadecane). We did not observe any skin reactions or edema from these chemicals. Erythema was completely resolved after 24 h of the patch removal in case of xylene and hexadecane.     

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.     

The agarose diffusion method for ocular irritancy screening: cosmetic products,part i

Abstract

The cosmetics industry is the target of criticism from animal welfare and animal rights groups for its use of the Draize eye irritancy test to substantiate the safety of cosmetic ingredients and products. To date, the two main difficulties in the development of alternatives to the Draize test have been a lack of high correlation between in vitro alternative test results and in vivo Draize test results, and the inability to present typical cosmetic formulations to these alternative test systems. For these reasons it occurred to us to test cosmetic products with the agarose diffusion test. This test has been scientifically validated and is well-established as an in vitro alternative test to screen the toxicity of plastics in medical devices. Sixteen cosmetic products initially tested with the Draize eye irritancy test and skin irritation test were tested in the agarose diffusion method to determine whether zone of lysis and/or cell toxicity could be correlated with either Draize eye test results or primary irritation index (PII). Even though the sample size was small (16 cosmetic products exclusive of controls), 80% (4/5) of the samples positive in the Draize eye test were predicted by the agarose diffusion method. Eighty-two percent (9/11) of the Draize negative samples were predicted by this same method, for an overall correlation of 81 % between the agarose diffusion method and the results in the Draize eye irritancy test. Only 19% of the test materials were false positives (2/16) or false negatives (1/16), suggesting that the agarose diffusion model may be slightly more sensitive than the Draize eye method. No correlation between the agarose diffusion test and the primary skin irritation test results could be established. These results indicate a high degree of correlation between an in vitro screening test as an alternative to the Draize eye irritancy test and permit testing of oil-in-water emulsions (both pigmented and nonpigmented), water-based suspensions, petroleum-distillate-based suspensions, solutions, physical mixtures of waxes, and physical mixtures of dry powders in this alternative test system.     

Polymeric microparticles-based formulation for the eradication of cutaneous candidiasis: development and characterization

Abstract

Cutaneous candidiasis is a common topical fungal infection which may be more prominent in patients associated with AIDS. It is usually treated by conventional formulations such as cream, gel, which show various adverse effects on skin along with systemic absorption. To overcome these drawbacks, various novel drug delivery systems have been explored. Poly(lactic-co-glycolic acid) (PLGA)-based microparticulate systems have shown good dermal penetration after topical application. Therefore, in the present study clotrimazole-loaded PLGA microspheres were prepared for targeted dermal delivery. Microspheres were prepared by using a single emulsification (oil-in-water, O/W) evaporation technique and characterized for different parameters. Prepared microparticulate systems were dispersed in Carbopol 934® gel and antifungal activity was carried out on experimentally induced cutaneous candidiasis in immunosuppressed guinea pigs. Particle size of optimized formulation was 2.9?µm along with 74.85% entrapment of drug. Skin retention studies revealed that drug accumulation in the skin was higher with microspheres gel as compared to marketed gel. Confocal microscopy of skin further confirmed penetration of microspheres up to 50?µm into the dermal region. In-vivo antifungal activity studies demonstrated that microsphere gel showed better therapeutic activity, lowest number of cfu/ml was recorded, as compared to marketed gel after 96?h of application. Based on the results of the study, it can be concluded that PLGA microparticles may be promising carriers to deliver clotrimazole intradermally for the treatment of invasive fungal infections.     

薄荷脑鼻腔原位凝胶剂的制备及安全性研究

目的 制备薄荷脑鼻用原位凝胶剂,并对其进行安全性考察。方法 采用去乙酰结冷胶为材料制备离子敏感性原位凝胶。考察鼻腔原位凝胶对蟾蜍鼻黏膜纤毛的毒性及大鼠鼻黏膜的影响;并进行家兔皮肤刺激实验和豚鼠皮肤过敏实验,观察皮肤反应并评分。结果 薄荷脑鼻用原位凝胶剂对蟾蜍鼻黏膜纤毛无显著毒性,对大鼠鼻黏膜形态及细胞分化无显著影响;对家兔完整皮肤无刺激作用,豚鼠皮肤无过敏反应。结论 薄荷脑鼻用原位凝胶剂具有制备工艺简便、纤毛毒性低、生理相容性好的优点,开发为经鼻给药系统可行性良好。     

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.