Development and evaluation of topical formulations that contain hydroethanolic extract from Schinus terebinthifolia against HSV-1 infection

Abstract The therapeutic drugs to treat Herpes simplex virus (HSV) infections have toxic side effects and there has been an emergence of drug-resistant strains. Therefore, the search for new treatments for HSV infections is mounting. In the present study, semi-solid formulations containing a crude hydroethanolic extract (CHE) from Schinus terebinthifolia were developed. Skin irritation, cutaneous permeation, and in vivo therapeutic efficacy of the formulations were investigated. Treatment with the ointment formulations did not result in any signs of skin irritation while the emulsions increased the thickness of the epidermis in Swiss mice. The cutaneous permeation test indicated that the CHE incorporated in the formulations permeated through the skin layers and was present in the epidermis and dermis even 3 h after topical application. In vivo antiviral activity in BALB/c mice treated with the CHE ointments was better than those treated with the CHE emulsions and did not significantly differ from an acyclovir-treated group. Taken together, this suggests that the incorporation of CHE in the ointment may be a potential candidate for the alternative topical treatment of herpetic lesions.

Antimicrobial and wound healing activity of Ixora coccinea leaf extract in hydrogel formulation

@#<p style="text-align: justify;"><strong>Objectives.</strong> The purpose of this study was to evaluate the antimicrobial and wound healing property of the preformulated hydrogel containing the methanolic leaf extract of Ixora coccinea, as well as its acute dermal irritation using New Zealand rabbits.</p><p style="text-align: justify;"><strong>Methods.</strong> Mature dried leaves of I. coccinea was subjected to extraction using maceration and was concentrated in vacuo. Sodium carboxymethylcellulose and gelatin were used to create hydrogel in which the crude extract was incorporated. Physicochemical properties of the extract and preformulated hydrogel were characterized, while its antimicrobial activities against Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis were determined using the agar well method and compared to the standard drug 2% w/v mupirocin ointment. A wound excision model in rats was used to determine the wound healing property of the preformulated hydrogel against povidone-iodine ointment. Lastly, animal testing was performed following the OECD Guidelines and upon approval of the IACUC Committee.</p><p style="text-align: justify;"><strong>Result.</strong> The preformulated hydrogel was effective against S. aureus (p-value ? 0.001) but resistant to P. aeruginosa and S. epidermidis. Furthermore, the wound contraction rate in groups treated with preformulated hydrogel (p-value = 0.006) is significantly higher than in groups treated with hydrogel base and povidone-iodine. Moreover, no dermal erythema and edema were observed with albino rabbits.</p><p style="text-align: justify;"><strong>Conclusion.</strong> The preformulated hydrogel with I. coccinea methanolic leaf extract is non-irritating, effective against staphylococcal infections commonly found in wounds. Hence, it is a good substitute for povidone-iodine in wound treatment.</p>

Effect of hot or warm property on skin toxicity of essential oil as penetration enhancer and its mechanism / 中国中药杂志

To compare the effect of hot or warm property of Chinese medicine(CM) on the skin toxicity of essential oils(EOs) as penetration enhancer in vitro and in vivo, and explore the mechanism. EOs were extracted from WIM of Bichengqie(Litseae Fructus), Dingxiang(Flos Syzygii Aromatici), Huajiao(Pericarpium Zanthoxyli Bungeani), and Xiaohuixiang(Fructus Foeniculi) with warm property, and Ganjiang(Rhizoma Zingiberis), Gaoliangjiang(Rhizoma Alpiniae Officinari), Hujiao(Fructus Piperis), and Wuzhuyu(Fructus Evodiae Rutaecarpae) with hot property, respectively. Then the in vitro toxicity was evaluated by human keratinocyte cytotoxicity. In vivo skin irritation potency was also evaluated through pathological observation after topical administration. The components, especially those located in stratum corneum, were analyzed by GC-MS. The main components, namely monoterpenes and sesquiterpenes, of EOs extracted from CM with hot property,were detected for the interaction with keratino-lipid ceramide 3 by molecular simulation technology; and the interaction energy value was calculated based on the optimal conformation. It was found that the skin cell toxicity of EOs from CM with hot property was significantly higher than that of EOs from CM with warm property. However, there was no significant difference between them by in vivo skin irritation evaluation. Whether from CM with hot property or warm property, EOs showed a significant reduced toxicity compared with azone. Sesquiterpenes(33.56%±19.38%) were found to be one of the main components in EOs from CM with hot property, while almost no sesquiterpenes was found in EOs from CM with warm property. After topical administration of EOs from CM with hot property, sesquiterpenes were demonstrated to be prone to locate in stratum corneum. The results of molecular simulation also revealed that the interaction between sesquiterpenes and ceramide 3 was significantly stronger than that of monoterpenes(P<0.01). In conclusion, the location of sesquiterpenes in stratum corneum resulted in the significant difference between in vitro skin cell toxicity and in vivo skin irritation potency. The EOs from CM with hot property shall be taken into account for further development of potent penetration enhancer.

Assessment of the Dermal Acute Irritation Potential of Natural Veterinary Medicine Minyak Rajas in Albino Rabbits

Aims: This study was designed to assess the potential for acute dermal irritation of natural veterinary medicine Minyak Rajas (produce by SonggolangitPersadaLimited Company, Bali, Indonesia) in albino rabbits. It is a rather thick liquid which contains various medicinal herbal extracts, formulated with effective microorganism technology. This medicine is effective in the treatment of skin infections and inflammation, wounds, intestinal worms and digestive disorder. Additionally, it works for game fowl muscle strengthening.Place and Duration of Study:This study was conducted at the Veterinary Pharmacy and Pharmacology Laboratory, Faculty of Veterinary Medicine, Udayana University, between April 2020 and May 2020.Methodology:Experimental animals used were three male albino rabbits (Oryctolaguscuniculus) in healthy conditions and weighing of >2 Kg. Test procedures followed the guidelines of Organisation for Economic Cooperation and Development, and chemicals used were applied in a single dose of 0.5 ml on animal skins, with untreated skin as a control.Results:Very slight erythema was found after the Minyak Rajas application and the lesion was about 48 hours.Overall, no severe erythema, edema or other skin lesions were observed. According to the AmandedDraize system, the Primary Irritation Indexes of 0.16 is categorized as non-irritating.Conclusion:We conclude that the natural veterinary medicine of MinyakRajasis safe to be used

Study on Skin Irritation of Clobetasone Butyrate Cream in Rabbits and Its Skin Sensitization in Guinea Pigs / 中国药房

OBJECTIVE：To study the skin irritation and se nsitization of domestic generic drug Clobetasone butyrate cream ， and to compare it with commercial drug （original drugs ）. METHODS ：The skin irritation test was conducted on rabbits. Totally 24 rabbits were randomly divided into test preparation intact skin group ，test preparation abraded skin group ，commercial drug intact skin group and commercial drug abraded skin group ，with 6 rabbits in each group. 0.5 mL test preparation or commercial drug was administered to the left side of intact or abraded skin and the same amount of excipient on the right side of each rabbit twice a day for consecutive 7 days. The irritation of the drug to the rabbit skin was observed ，and the erythema and edema of the skin were scored；the skin of administration site was taken at 72 h after last administration and the end of 7 d after drug withdrawal for histopathological examination. The skin sensitization test （Buehler test ）was carried out on guinea pigs. Totally 60 guinea pigs were randomly divided into test preparation group （n＝20），commercial drug group （n＝20），positive control group （n＝10）and excipient control group （n＝10）. 0.2 mL test preparation or commercial drug was administrated to the left side of the rib abdomen skin of each guinea pig at the 0，7th，14th day to induce model ，and an equal amount of corresponding preparation was administered to the right side in the same way at the 28th day for stimulation. Hypersensitive response such as erythema and edema were observed and scored at 24 h and 48 h after the stimulation. The incidence of hypersensitive response was then calculated. RESULTS：In skin irritation test of rabbits ，no erythema and edema was caused by the test preparation or commercial drug on intact skin of rabbits ；scores of skin irritation was 0；there was no dermal irritation. Both test preparation and commercial drug caused transient slight erythema on abraded skin of a few rabbits ；scores of intact and abraded skin irritation were 0-0.33；there was no dermal irritation. There was no statistical significance among groups. No dermal pathological changes were observed. In skin sensitization test of guinea pig ，no hypersensitive response such as erythema and edema was found on the skin of guinea pigs in both test preparation and commercial drug groups ；both score and the incidence of hypersensitive response were 0. Compared with excipient control group ，there was no statistical significance of average score and the incidence of hypersensitive response in test preparation group and commercial drug group. CONCLU- SIONS：In skin irritation test of rabbits and skin sensitization test of guinea pigs ， the evaluation results of generic Clobetasone butyrate cream are the same as those of the original drug. It has no irritation to the skin of rabbit ，and no sensitization to the skin of guinea pigs.

In Vivo Evaluation Of Tazarotene Solid Lipid Nanoparticles Gel For Topical Delivery

The purpose of this research work was to develop and optimize the Solid Lipid Nanoparticles (SLNs) of Tazarotene for the effective topical delivery in the treatment of psoriasis. Tazarotene loaded SLNs were prepared by hot homogenization followed by the ultrasonication using Taguchi’s design and based on the results further investigation was made using central composite design. The lipid Dynasan-116, surfactant poloxomer-188 and co surfactant egg lecithin resulted in better percent drug loading and evaluated for particle size, zeta potential, TEM, drug entrapment efficiency, in vitro drug release and stability. All parameters were found to be in an acceptable range. In vitro drug release of optimized SLN formulation (F1) was found to be 98.12 ± 1.52%, whereas pure drug release was 42.12 after 60 min. The optimized formulation was incorporated into the gel. The release rate (flux) of tazarotene across the membrane and excised skin differs significantly. The accumulative amount of Tazarotene in skin from SLN based gel formulation and marketed gel were 41.12 ± 0.12 mg and 30.02 ± 0.04 mg respectively. This result supported our hypothesis made in skin permeation studies on rat skin. From histopathological studies the microscopic observations indicate that the optimized SLN formulation, SLN based gel formulation and marketed gel has no significant effect on the microscopic structure of the skin. The skin-irritation studies indicated that SLN based gel containing Tazarotene did not show any sign of skin irritation as compared to moderate erythema shown by marketed gel formulation (Tazret® gel) after 72 h of application. Thus, SLN based gel formulation demonstrated advantage over marketed formulation in improving the skin tolerability of Tazarotene indicating their potential in improving patient acceptance and topical delivery of Tazarotene.

Investigation of Skin Irritation of Essential Oils from Interior-warming Medicines / 中国实验方剂学杂志

Objective:To investigate the skin irritation of essential oils(EOs) extracted from interior-warming medicines. Method:Three EOs from interior-warming medicines(Cinnamomi Cortex, Caryophylli Flos and Alpiniae Officinarum Rhizoma) were selected as research objects.The in vitro skin cytotoxicity and in vivo skin irritation of these EOs were determined and compared.Moreover, the skin irritation was also predicted by the novel skin test panels. Result:Toxicity of these three EOs to human skin fibroblasts(HSF) was significantly different, half-inhibitory concentration(IC50) values of EOs from Cinnamomi Cortex, Alpiniae Officinarum Rhizoma and Caryophylli Flos were (11.16±0.28), (53.33±1.71), (226.70±17.61) mg·L-1, respectively.However, in vivo skin irritation evaluation showed that the local toxicity of these three EOs was in the order of EO of Cinnamomi Cortex > EO of Caryophylli Flos > EO of Alpiniae Officinarum Rhizoma. The evaluation results of skin test panels for these three EOs were in accordance with the results of in vivo skin irritation evaluation. Conclusion:Toxicity of these three EOs against skin cells in vitro is inconsistent with their in vivo skin irritation. Skin test panels are expected to be able to accurately predict in vivo skin irritation of EOs instead of cytotoxicity evaluation.

IL-1 Receptor Antagonist Reduced Chemical-Induced Keratinocyte Apoptosis through Antagonism to IL-1α/IL-1β

Extracellular interleukin 1 alpha (IL-1α) released from keratinocytes is one of the endpoints for in vitro assessments of skin irritancy. Although cells dying via primary skin irritation undergo apoptosis as well as necrosis, IL-1α is not released in apoptotic cells. On the other hand, active secretion has been identified in interleukin-1 receptor antagonist (IL-1ra), which was discovered to be a common, upregulated, differentially-expressed gene in a microarray analysis performed with keratinocytes treated using cytotoxic doses of chemicals. This study examined whether and how IL-1ra, particularly extracellularly released IL-1ra, was involved in chemically-induced keratinocyte cytotoxicity and skin irritation. Primary cultured normal adult skin keratinocytes were treated with cytotoxic doses of chemicals (hydroquinone, retinoic acid, sodium lauryl sulfate, or urshiol) with or without recombinant IL-1ra treatment. Mouse skin was administered irritant concentrations of hydroquinone or retinoic acid. IL-1ra (mRNA and/or intracellular/extracellularly released protein) levels increased in the chemically treated cultured keratinocytes with IL-1α and IL-1β mRNAs and in the chemically exposed epidermis of the mouse skin. Recombinant IL-1ra treatment significantly reduced the chemically-induced apoptotic death and intracellular/extracellularly released IL-1α and IL-1β in keratinocytes. Collectively, extracellular IL-1ra released from keratinocytes could be a compensatory mechanism to reduce the chemically-induced keratinocyte apoptosis by antagonism to IL-1α and IL-1β, suggesting potential applications to predict skin irritation.

Preparation of tea tree oil gel and its pharmacodynamic study and irritation evaluation / 中草药

Objective To study the prescription and preparation technology of tea tree oil gel, and evaluate its anti-inflammatory efficacy, antibacterial effect and the irritation. Methods The tea tree oil gel was prepared using the carbomer-940 as gel matrix, Cremophor RH-40 and 1,2-propylene glycol as solvents. The appearance characters, pH value, viscosity, moisture retention, drug content, and the stability were observed. The anti-inflammatory efficacy, the antibacterial effect and the irritation of tea tree oil gel were evaluated. Results The prescription of tea tree oil gel was selected as following tea tree oil (1.0%), Cremophor RH-40 (5.0%), 1,2-propylene glycol (5.0%), Carbomer-940 (0.6%), glycerol (8.0%), with distilled water 100 g, adjusting pH to 5.0 by triethanolamine. The gel exhibited transparent, well uniformity, appropriate viscosity and fine coating expansion performance, with pH value of 5.52 ± 0.03, viscosity at (48 782 ± 25) mPa•s, the moisture retaining rate of (93.32 ± 0.38)% for 24 h test, containing tea tree oil of (9.55 ± 0.10) mg/g. The inhibition rate of tea tree oil gel on the mouse auricle swelling was 46.15%, which was significantly different as compared to the negative control group (P < 0.01). The diameters of inhibition zone of the gel against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa respectively was (15.50 ± 0.96), (15.25 ± 2.36), and (15.75 ± 1.91) mm. The half hemolysis rate (LC50) and the hemoglobin degeneration index (DI) respectively were 456 157 mg/L and 157.98%. The tea tree oil gel had no eye irritation in rabbits based on the value of LC50/DI 2 887.44. Fourteen consecutive’days administration indicated that the tea tree oil gel had no skin irritation in rabbits. The illumination score of irritative reaction to the rabbit skin was 0.125 after a single administration, while that was 0.036 after successive administration experiment. The results of high speed centrifugalization cold- resistance and heat-resistance tests showed that the preparation exhibited good stability, which needed to be kept tightly in a cool place and protected from light. Conclusion The formulation design was reasonable, while the preparation technology was simple, corresponding to the main index of the gel for topical application, with good anti-inflammatory efficacy, antibacterial effect and safety, which offered the basis for further research and development of tea tree oil.

In vivo transdermal permeation-enhancement activity and skin irritation of eucalyptus oil by using microdialysis technique / 中草药

Objective To evaluate the skin irritation of eucalyptus oil and its in vivo transdermal penetration enhancement properties by using the cutaneous microdialysis technique. Methods The CCK-8 assay was used to measure the toxicity of eucalyptus oil on HaCaT cells, and the TEWL values of the rat skin was determined to investigate the effect of eucalyptus oil on the skin integrity and irritation. Ligustrazine and geniposide were chosen as lipophilic and hydrophilic model drugs, respectively, and their microdialysis probe in vivo recoveries were determined using the retrodialysis method. After treatment with eucalyptus oil, the skin pharmacodynamics behaviors of two model drugs were investigated to evaluate its penetration-enhancement activity. Results The cytotoxicity test revealed there IC50 value of eucalyptus oil to HaCaT cells was 2.452 mmol/L, which was significantly higher than that of chemical penetration enhancer Azone (IC50, 0.266 mmol/L). Meanwhile, the eucalyptus oil had a certain impact on the rat skin TEWL values, but it was weaker than Azone, this implied that the eucalyptus oil had a mild skin irritation. The in vivo transdermal microdialysis tests revealed that the enhancement ratios (ER) of ligustrazine and geniposide were 11.40 and 13.79, respectively, indicating that eucalyptus oil could effectively facilitate the transdermal permeation of both of lipophilic and hydrophilic drugs. Although the penetration enhancement property was generally weaker than Azone, the ER value of eucalyptus oil was closely approximate to Azone. Conclusion The eucalyptus oil could promote the transdermal permeation of both lipophilic and hydrophilic drugs with mild skin irritation, which provided the data support for its application in topical preparation.

Experimental study on skin irritation and anaphylaxis of liquid bandage / 医疗卫生装备

Objective To observe the skin irritation and anaphylaxis of the liquid bandage to facilitate its safety evaluation. Methods In case of skin irritation test,some New Zealand rabbits were divided into an unaffected skin group and an affected skin group, and had their skin observed for erythema, edema and etc after undergoing 1-d and 7-d administration respectively;in case of anaphylaxis,the guinea pigs went through drug sensitization respectively at the 1st,7th and 14th days and experienced re-sensitization 14 days after,and the symptoms of anaphylaxis were observed such as erythema and edema. Results The liquid bandage had no irritation to the unaffected and affected skin of New Zealand rabbit by single or multiple administration with the irritation mean value being lower than 0.5.There were no anaphylaxis symptoms such as erthema and edema found in the guinea pig by the liquid bandage.Conclusion The liquid bandage proves its skin safety by non-irritation to the unaffected and affected skin of New Zealand rabbit and non-anaphylaxis to the guinea pig.

Quality Evaluation and Transdermal Study of Matrine Microemulsion-based Hydrogel / 中国药师

Objective: To study the quality and transdermal properties of matrine microemulsion-based hydrogel (MBH) to provide basis for the development of the preparation.Methods: The stability of MBH was observed at 4 ℃ for 3 months and the changes of particle appearance, viscosity, pH and matrine content were observed.The transdermal permeation of MBH was investigated by a dual chamber permeation and diffusion device with excised mouse skin as the barrier.Taking rabbits as the experimental subjects, the irritation of MBH to the normal skin and damaged skin was investigated.Results: The appearance, viscosity, pH and matrine content of MBH at 4 ℃ in 3 months did not change significantly.In vitro transdermal test showed that MBH had a good penetration rate on mouse skin, and no skin irritation occurred after single or multiple administrations.Conclusion: MBH has good stability and high rate of transdermal penetration without skin irritation, which is a promising drug delivery system of matrine with good application prospects.

Study on the Skin Irritation of Hongzhi Gutong Cataplasm in Rabbits / 中国药房

OBJECTIVE:To study the safety of percutaneous administration of Hongzhi gutong cataplasm. METHODS:Rab-bits were taken for single dose in complete skin irritation test(n=4),single dose in damaged skin irritation test(n=4)and multi-ple doses in complete skin irritation test(n=4). The left and right sides of the skin respectively paste 3 cm×3 cm blank matrix and Hongzhi gutong cataplasm for 24 h(calculated by crude drug of 0.14 g). After removing tape 1,24,48,72 h,the erythema and edema in hair removal site of rabbits in the former 2 tests were observed;after 24 h of administration,the rabbits in the last group were administrated again after exposing the administration area for 1 h,repeated 3 times,the erythema and edema in hair removal site after removing tape the first,second time and 1,24,48,72 h in the third time were respectively observed. RESULTS:In the 3 experiments,the scores of erythema and edema of all rabbits were 0,and skin irritation was evaluated as no irritation. CONCLU-SIONS:Hongzhi gutong cataplasm has no skin irritation in rabbits.

Evaluation of Rabbit Skin Irritation and in vitro Transdermal Absorption of Diclofenac Sodium Microemul-sion / 中国药房

OBJECTIVE:To investigate the property,skin irritation and in vitro transdermal absorption of Diclofenac sodium microemulsion(DS-ME),and to explore the feasibility of local external use of it. METHODS:The content of DS in DS-ME was determined by ultraviolet spectrophotometry. The distribution of particle size was determined by laser particle size analyzer. The ef-fects of DS-ME and blank micro-emulsion on normal skin of single administration,normal skin of multiple administration and dam-aged skin of single administration were investigated by rabbit skin irritation test. The transdermal parameters of DS-ME and commer-cially available DS gel through isolated skin of mice were compared by Franz diffusion cell. RESULTS:The prepared DS-ME was O/W microemulsion with particle size of(30.140±9.020)nm. Compared with blank ME,DS-ME had no significant difference in rabbit skin irritation score. Steady permeation rates of DS-ME and commercially available DS gel were 34.16 and 18.62 μg/(cm2·h), respectively;the permeation coefficient of them were 1.029 and 0.561 cm/h;the delay time were 0.124 2 and 0.367 2 h. CONCLU-SIONS:The particle size of DS-ME is small and not irritant to skin,and can improve transdermal absorption rate of DS.

Increased Skin Irritation by Hydroquinone and Rsetinoic Acid Used in Combination

BACKGROUND: Hydroquinone (HQ) is frequently combined with retinoic acid (RA) to enhance lightening efficacy, which may also affect skin irritancy. Although skin irritation leads to postinflammatory hyperpigmentation, little research has been performed to compare skin irritancy between each component and the combination. OBJECTIVE: This study was done to examine whether HQ-RA combination increased skin irritation induced by HQ or RA alone. METHODS: Patch testing was performed using maximum therapeutic and higher concentrations of HQ and RA in 10 volunteers, and then, it was performed using their popular therapeutic concentrations and combination in the other 20 volunteers. In vitro irritation was also assessed in primary cultured normal human keratinocytes treated with 80% and 50% cell survival doses of HQ, 80% cell survival dose of RA, and their combination. RESULTS: The combination in patch testing induced stronger erythema than the corresponding concentrations of HQ and RA, which was remarkable with use of combination of higher concentrations. In cultured keratinocytes, the RA combination significantly decreased cell viability, but increased cytotoxicity and extracellular interleukin 1 alpha release with corresponding doses of HQ. CONCLUSION: The results of patch tests and in vitro irritation assessment tests suggested that HQ and RA increased skin irritation when used in combination.

Safety Study of Polyisobutylene Gutong Plaster by Transdermal Administration / 中国药房

OBJECTIVE:To investigate the safety of Polyisobutylene (PIB) Gutong plaster by transdermal administration. METHODS:66 rabbits were randomly divided into a normal group,a group with intact skin and a group with damaged skin. The latter two groups were respectively re-divided into PIB group,the groups of low,medium and high-dose PIB Gutong plaster and Gutong plaster group. An acute toxicity test was conducted on the rabbits,which 14 d of continuous observation was made 24 h af-ter transdermal administration. Another 60 rabbits were divided into several groups as above except for a normal group. A single pri-mary skin irritation test was conducted on them,where skin irritation reactions were recorded 6 h after a single administration based on intra-individual left/right self comparison method. 70 guinea pigs were randomized into a negative control group (vase-line),a PIB group,a positive control group(2,4-dinitrochlorobenzene),a Gutong plaster group and the groups of low,medium and high-dose PIB Gutong plaster,which were dosed for sensitization,followed by a skin sensitization test. RESULTS:No obvi-ous toxicity symptoms could be seen after administration of PIB Gutong plaster. The rabbits’intact or damaged skin had no irrita-tion response to PIB and low and medium-dose PIB Gutong plaster. PIB Gutong plaster caused no irritation response in the rabbits’ intact skin,but slight irritation in damaged skin 1 h after administration. The allergic reaction incidence of the positive control group of guinea pigs was 100% while that of any other groups was 0. CONCLUSIONS:The PIB Gutong plaster is safe for trans-dermal administration.

Liquid crystalline systems containing Vitamin E TPGS for the controlled transdermal nicotine delivery

ABSTRACT Transdermal nicotine patches have been used in smoking cessation therapy, suggested for the treatment of skin disorders with eosinophilic infiltration and have been found to improve attention performance in patients with Alzheimer's disease and age-associated memory impairment. However, skin irritation with extended patch use is still a problem. The aim of this work was to develop a simple to prepare liquid crystalline system containing vitamin E TPGS that would be able to control nicotine delivery and reduce irritation and sensitization problems. The liquid crystalline phases were macroscopically characterized by visual analysis and examined microscopically under a polarized light microscope. Topical and transdermal delivery of nicotine were investigated in vitro using porcine ear skin mounted on a Franz diffusion cell. Nicotine skin permeation from the developed cubic phase followed zero-order kinetics (r = 0.993) and was significantly enhanced after 12 h when compared to the control formulation (nicotine solution) (p < 0.05) (138.86 ± 20.44 and 64.91 ± 4.06 μg/cm2, respectively). Cubic phase was also able to target viable skin layers in comparison to control solution (8.18 ± 1.89 and 2.63 ± 2.51 μg/cm2, respectively). Further studies to evaluate skin sensitization and irritation are now necessary.

RESUMO Adesivos transdérmicos de nicotina são utilizados para cessação de fumar, tratamento de problemas de pele com infiltração de eosinófilos e para melhorar a atenção em pacientes com doença de Alzheimer e enfraquecimento da memória associada à idade. No entanto, a irritação da pele com o uso prolongado dos adesivos ainda é um problema. O objetivo deste trabalho foi desenvolver sistema líquido cristalino (SLC) de preparo simples contendo vitamina E TPGS capaz de controlar a liberação de nicotina e reduzir os problemas de irritação cutânea. Os SLCs foram caracterizados por análise visual e microscopia de luz polarizada. As administrações tópica e transdérmica de nicotina foram investigadas in vitro utilizando pele de orelha de porco em célula de difusão de Franz. A permeação da nicotina veiculada pela fase cúbica desenvolvida seguiu cinética de ordem zero (r = 0,993) e foi significativamente maior do que o controle (solução de nicotina) após 12 h (p < 0,05) (138,86 ± 20,44 e 64,91 ± 4,06 µg/cm2, respectivamente). A fase cúbica também promoveu aumento da penetração de nicotina nas camadas viáveis da pele quando comparado ao controle (8,18 ± 1,89 e 2,63 ± 2,51 µg/cm2, respectivamente). Estudos futuros para avaliar a sensibilização e irritação da pele são necessários.

Permeação cutânea: desafios e oportunidades / Skin permeation: challenges and opportunities

O transporte de fármacos pela via transdérmica tem vindo a despertar um grande interesse, uma vez que constitui uma alternativa para ultrapassar as limitações de outras vias, como a oral e parenteral. No entanto, esta via ainda se destina apenas a um grupo restrito de fármacos, devido ao fato de que a pele apresenta uma baixa permeabilidade ao movimento de moléculas estranhas, como consequência da função barreira desempenhada pela camada córnea. Diversas estratégias têm sido desenvolvidas para contornar a barreira da pele com o objetivo de aumentar a permeação de fármacos, abrangendo métodos passivos ou ativos. O presente trabalho visa à revisão dessas estratégias, abordando os respetivos mecanismos de ação, bem como algumas combinações entre os diferentes métodos que têm demonstrado um efeito sinérgico e abordando, ainda, o problema da irritação da pele que pode advir da administração de fármacos por esta via.

Transdermal drug delivery has shown to be an interesting alternative to overcome limitations of conventional routes, such as the oral and parenteral ones. Nonetheless, the practical applications still remains limited to a narrow range of drugs, due to the skin barrier layer of the stratum corneum, which provides a low permeability to exogenous molecules. This review focuses on the strategies developed to enhance drug permeation, which include passive and active methods, and their respective mechanisms of action, as well as the combination of different methods that have shown to work in synergy. The problem of skin irritation that may result from the administration of drugs by this route is also addressed.

Irritation of a new specimen preservation solution on the skin,eye of rabbits and its effect for specimens preser-vation / 局解手术学杂志

Objective To conduct the preliminary toxicology tests and evaluate the preservation effect on a new specimen preservation solution in order to provide scientific basis for its application security. Methods Twenty-four New Zealand white rabbits were randomly di-vided into the normal saline group, the formalin preservation group,the mixture group,and the new preservation solution group. Recorded the irritation of different solution on the skin,eye of rabbits,the effect of liver sample preservation in different solution,and the evaporation rate of these solution. And to find a set of preservative solution which is more suitable for preservation of specimens and can reduce the cost. Results The new preservation solution is stimulus on rabbit skin and eye,and it is stronger than the formaldehyde group. Compared with the other three groups,the mixture group has the best preservation effect, and the new preservation solution group has a better preservation effect than the formalin preservation solution group. Conclusion The 1∶1 mixture solution of the new preservation solution and formaldehyde is more suitable preservation solution and it can reduce the costs.

The Behind the Knee (BTK) as an Innovative Test Model for Mechanical and Chemical Irritation, Lotion and Dye Transfer and Testing on Compromised Skin.

Aims: The aim of this manuscript is to present innovative applications of the BTK model that can potentially contribute additional aspects of safety evaluations for a broader range of products and materials intended for prolonged skin contact. Study Design and Methodology: The basic BTK protocol is one 6-h exposure per day for 4 days. Modification to the basic protocol were made for individual studies, as needed. Results: Studies using fabrics, tissues and films indicate the BTK may be well suited to evaluating these materials for skin compatibility. The BTK test discriminated between; different fabrics, drying methods of the same fabric, similar toilet tissue products, and two similar topsheet films used as coverings on the surface of a range of absorbent consumer products. The method was used successfully to measure the transfer of lotion, and lotion skin benefits from lotioned absorbent products. Conclusion: Studies demonstrate that the utility of the BTK goes beyond the original intent of evaluating the potential skin effects of feminine protection products. The ability to compare fabrics, tissues and films indicate the test model may be useful in the development broad range of absorbent consumer products and in textile development. The utility of the model in measuring the transfer of lotion and other materials from products to the skin surface has the potential to fill an important gap in the development of quantitative exposure assessments. Added endpoint measures, such as enhanced visual scoring and sensory effects further increase the ability to differentiate between very similar products without requiring other protocol modifications.