Evidence of Cannabidiol Effectiveness Associated or Not with Tetrahydrocannabinol in Topical Administration: A Scope Review.

Cannabis sativa is a plant of the Cannabaceae family, whose molecular composition is known for its vast pharmacological properties. Cannabinoids are the molecules responsible for Cannabis sativa potential effects, especially tetrahydrocannabinol and cannabidiol. Scientific development has shown interest in the potential of cannabidiol in various health conditions, as it has demonstrated lower adverse events and great pharmacological potential, especially when administered topically. The present study aims to carry out a scoping review, focusing on the use of cannabidiol, in vivo models, for topical administration. Thus, the methodological approach used by the Joanna Briggs Institute was applied, and the studies were selected based on previously established inclusion criteria. Even though more information regarding the dose to achieve pharmacological potential is still needed, cannabidiol demonstrated potential in treating and preventing different conditions, such as glaucoma, atopic dermatitis, epidermolysis bullosa, and pyoderma gangrenosum.

Identification of Epstein-Barr virus after topical treatment for oral hairy leukoplakia: A preliminary study.

BACKGROUND: This study evaluated the presence of Epstein-Barr virus type 1 (EBV-1) DNA in patients living with HIV, before and after three different topical therapy protocols for oral hairy leukoplakia (OHL). METHODS: The sample consisted of five patients treated with topical solution of 25% podophyllin resin; six with 25% podophyllin resin plus 5% acyclovir cream; and four with 25% podophyllin resin plus 1% penciclovir cream. DNA was extracted from OHL scrapings and amplified by the PCR using specific primers for EBV-1 (EBNA-1). RESULTS: Clinical healing of OHL lesions was observed across all treatment groups over time. At baseline, EBNA-1 was detected in all OHL lesions. After treatment, OHL samples from three patients treated with 25% podophyllin resin plus 5% acyclovir cream and from one patient treated with 25% podophyllin resin plus 1% penciclovir cream exhibited negative EBNA-1 viral gene encoding. Despite the clinical resolution of OHL, 11 patients (73.3%) showed EBNA-1 positivity immediately after the lesion disappeared. Three patients (20%) treated with podophyllin resin displayed both EBNA-1 positivity and a recurrence of OHL, in contrast to no recurrence in the other two groups. CONCLUSIONS: These findings suggest potential associations between treatment formulations, EBNA-1 persistence, and the recurrence of OHL lesions.

Norcantharidin Nanoemulsion Development, Characterization, and In Vitro Antiproliferation Effect on B16F1 Melanoma Cells.

Melanoma is a highly lethal type of cancer that has had an increase in incidence in the last decades. Nevertheless, current therapies lack effectiveness and have highly disabling side effects, which calls for new therapeutic strategies. Norcantharidin (NCTD) is an acid derivative with potential antitumor activity isolated from natural blister beetles. However, its solubility limitations restrict its use. To address this issue, we developed an oil-in-water nanoemulsion using commonly available cosmetic ingredients, which increased NCTD solubility 10-fold compared to water. The developed nanoemulsion showed a good droplet size and homogeneity, with adequate pH and viscosity for skin application. In vitro drug release studies showed a sustained release profile, ideal for prolonged therapeutic effects. Accelerated stability studies proved that the formulation was reasonably stable under stress conditions, with particle separation fingerprints, instability index, particle size, and sedimentation velocity analyses being conducted. To assess the therapeutic potential of the developed formulation, in vitro studies were conducted on melanoma B16F1 cells; results showed an IC50 of 1.026 +/- 0.370 mg/kg, and the cells' metabolic activity decreased after exposure to the NCTD nanoemulsion. Hence, a new "easy-to-make" nanoformulation with therapeutic potential on melanoma cells was developed, as a possible adjuvant for future melanoma treatment.

Topical therapy for pain management in malignant fungating wounds: A scoping review.

AIMS AND OBJECTIVES: To map and synthesise the existing literature on topical therapies for malignant fungating wounds pain management and the gaps involved. BACKGROUND: Most cancer patients with malignant fungating wounds suffer from wound-related pain, affecting their quality of life. Unfortunately, even though pain is a relevant symptom in cancer and palliative care, little is currently known about topical treatments' availability and impact on pain management. DESIGN: A scoping review following JBI® methodology METHODS: Searches were performed in CINAHL, LILACS, Embase, Web of Science, PubMed, Cochrane, NICE, Scopus, JBISRIR and grey literature, in English, Portuguese and Spanish, with no time limit. Two authors independently reviewed all citations and a third was called in case of divergence, and studies in adults with malignant fungal wounds reporting topical pain interventions were included. In addition, a data extraction tool for synthesis and thematic analysis was developed. This study followed the PRISMA-ScR Checklist. RESULTS: Seventy publications were selected from 796 records retrieved from databases. The studies mainly included non-systematic reviews and case studies with only six clinical trials. According to the narrative synthesis, twenty therapies were identified, including the use of wound dressings (58.6%), analgesic drugs (55.7%), topical antimicrobials (25.7%), skin barriers (15.7%), cryotherapy (5.7%) and negative pressure wound therapy (4.3%). Therapies were recommended to be applied to the wound bed or the periwound skin. In 68.5% of the studies, a standardised assessment for pain was not described. CONCLUSIONS: Topical therapies applied to malignant fungating wounds or periwound areas had been examined for pain management. However, their effectiveness was analysed in a few interventional studies, indicating the need for further primary studies to inform evidence-based practice. IMPLICATION FOR PRACTICE: Highlighted topical therapies for clinical practice consideration are opioids, anaesthetics and antimicrobials, with positive results described in randomised clinical trials. This study did not include patients.

Use of Chamomile Infusion to Mitigate Radiotherapy-Induced Dry Desquamation in Head and Neck Cancer Patients.

PURPOSE: To evaluate the effect of using a compress with Chamomilla recutita infusion in the regression of dry desquamation and in the prevention of moist desquamation in head and neck cancer patients undergoing radiotherapy. METHODS: A prospective intervention study was carried out from May 2019 to May 2021. In total, 43 participants were included, who were instructed to apply the compress with the infusion 3 times a day, after occurrence of dry desquamation. Skin evaluation took place daily from initiation of the intervention up to the end of radiotherapy. RESULTS: All the participants presented dry desquamation regression, where 65.1% (95% CI 50.1-78.1) had total regression until the end of radiotherapy, with a mean of 9 days of regression. Only 34.9% (95% CI 21.8-49.9) of the participants developed moist desquamation by the end of the radiotherapy sessions, with a mean accumulated dose of ionizing radiation of 50.9 Gy. CONCLUSION: This study highlighted the potential clinical benefits of using Chamomilla recutita in the regression of dry desquamation and in the prevention of moist desquamation.

Treatment of chronic wounds with methylene blue photodynamic therapy: A case report.

Methylene blue (MB) mediated photodynamic therapy (PDT) is an emerging treatment for different kinds of skin lesions and ulcers. Our case report aims to assess its potential in treating diabetic foot ulcers, venous leg ulcers, and pressure ulcers. Patients presented with complex chronic wounds larger than 40 cm2 with low healing potential. Once a week, patients had an aqueous formulation of MB at a concentration of 10 mg/mL (1% w/v) applied topically on their wounds, which were then irradiated with a light-emitting diode (LED) light source (660 nm, 3.8 J/cm2) with 9 mW/cm2 on tissue surface. Symptom improvement and recurrence rates were assessed with a long-term follow-up from 2018 to 2021. The results were satisfactory, with significant wound size reduction, and a decrease in aspects indicative of infection including odor, presence of exudates, and purulence. After methylene blue-mediated photodynamic therapy (MB-PDT), patients showed significantly reduced wound secretion, no signs of local reaction, and no adverse effects such as burning sensation, pain, itching, skin erythema, or general malaise.

Silver Nimesulide Complex in Bacterial Cellulose Membranes as an Innovative Therapeutic Method for Topical Treatment of Skin Squamous Cell Carcinoma.

Oxidative stress and inflammation act on skin squamous cell carcinoma (SSCC) development and progression. Curative therapy for SSCC patients is mainly based on surgical resection, which can cause various sequelae. Silver ions have in vitro activities over tumor cells, while nimesulide has antioxidant and anti-inflammatory activities. This study aimed to evaluate the effects of a silver(I) complex with nimesulide (AgNMS) incorporated in a sustained release device based on bacterial cellulose membrane, named AgNMS@BCM, on topic SSCC treatment. The antiproliferative effect of AgNMS complex was evaluated in the SCC4, SCC15 and FaDu SCC lines. AgNMS complex activity on exposure of phosphatidylserine (PS) residues and multicaspase activation were evaluated on FaDu cells by flow cytometry. The AgNMS@BCM effects were evaluated in a SSCC model induced by 7,12-dimethylbenzanthracene/12-o-tetradecanoyl-phorbol-13-acetate (DMBA/TPA) in mice. Toxicity and tumor size were evaluated throughout the study. AgNMS complex showed antiproliferative activity in SCC15 and FaDu lines in low to moderate concentrations (67.3 µM and 107.3 µM, respectively), and induced multicaspase activation on FaDu cells. The AgNMS@BCM did not induce toxicity and reduced tumor size up to 100%. Thus, the application of AgNMS@BCM was effective and safe in SSCC treatment in mice, and can be seen as a potential and safe agent for topic treatment of SSCC in humans.

Polymeric Biomaterials for Topical Drug Delivery in the Oral Cavity: Advances on Devices and Manufacturing Technologies.

There are several routes of drug administration, and each one has advantages and limitations. In the case of the topical application in the oral cavity, comprising the buccal, sublingual, palatal, and gingival regions, the advantage is that it is painless, non-invasive, allows easy application of the formulation, and it is capable of avoiding the need of drug swallowing by the patient, a matter of relevance for children and the elderly. Another advantage is the high permeability of the oral mucosa, which may deliver very high amounts of medication rapidly to the bloodstream without significant damage to the stomach. This route also allows the local treatment of lesions that affect the oral cavity, as an alternative to systemic approaches involving injection-based methods and oral medications that require drug swallowing. Thus, this drug delivery route has been arousing great interest in the pharmaceutical industry. This review aims to condense information on the types of biomaterials and polymers used for this functionality, as well as on production methods and market perspectives of this topical drug delivery route.

Effectiveness of local and topical anesthesia during gingival retraction / Eficácia da anestesia local e tópica durante a retração gingival

Objective: To compare the effectiveness of local and topical anesthesia during gingival retraction in prepared abutment teeth. Material and Methods: 72 patients desiring full mouth rehabilitation or bilateral fixed partial denture in the same arch were selected based on the inclusion criteria framed and were randomly allocated into Groups A and B of 36 each. Patients in Group A received gingival retraction with topical anesthesia and Group B received gingival retraction with infiltration anesthesia. All the patients were tested for pain, discomfort and bleeding during gingival retraction. Results: There was no significant difference in pain, discomfort and gingival bleeding (P >.05) during gingival retraction using topical and local anesthetic agents. Conclusion: Topical anesthesia was equally effective as infiltration anesthesia in managing the pain, discomfort and bleeding during gingival retraction by cord packing in prepared abutment teeth. (AU)

Objetivo: Comparar a eficácia da anestesia local e tópica durante a retração gengival previa a moldagem em dentes pilares preparados. Material e Métodos: Foram selecionados 72 pacientes indicados para reabilitação bucal total ou prótese parcial fixa bilateral na mesma arcada com base nos critérios de inclusão formulados e alocados aleatoriamente nos Grupos A e B com 36 pacientes cada. Os pacientes do Grupo A receberam retração gengival com anestesia tópica e no Grupo B receberam retração gengival com anestesia infiltrativa. Todos os pacientes foram testados para dor, desconforto e sangramento durante o procedimento. Resultados: Não houve diferença significativa na dor, desconforto e sangramento gengival (P>. 05) durante a retração gengival com anestésicos tópicos e locais. Conclusão: A anestesia tópica foi tão eficaz quanto a anestesia de infiltração no controle da dor, desconforto e sangramento durante a retração gengival com fio retrator gengival em dentes pilares preparados.(AU)

Wound healing by topical application of Momordica charantia L. formulations on mice.

BACKGROUND AND AIM: Momordica charantia is mainly characterized by its antimicrobial and antioxidant properties. The current study aimed to evaluate the healing activity of gel and cream formulations based on M. charantia on induced wounds in mice. MATERIALS AND METHODS: Acetonic extract of M. charantia was prepared and incorporated into gel and cream formulations. Mus musculus Balb/c (n=30) with induced injury were distributed into five groups: Group I (control - day 7), Group II (control - day 14), Group III (1% gel - day 7), and Group IV (1% gel - day 14) to which 1% M. charantia gel was dermally applied daily for 7 and 14 days, respectively, Group V (1% cream - day 7) and Group VI (1% cream - day 14) to which of M. charantia 1% cream were dermally applied daily for 7 and 14 days, respectively. Time of wound closure was determined during the experimentation; rats were euthanized with sodium pentobarbital 60 mg/kg/pc v.ip. for obtaining skin samples for histopathological analysis. RESULTS: Groups IV and VI showed a higher percentage of wound closure on day 14, and in histopathological analysis, effect was greater in Group VI with the presence of fibroblasts and abundant collagen and elastic fibers. CONCLUSION: M. charantia gel and cream showed wound healing activity on induced wounded mice; the most effective treatment was M. charantia 1% cream formulation.

An Overview on Topical Administration of Carotenoids and Coenzyme Q10 Loaded in Lipid Nanoparticles.

Carotenoids and coenzyme Q10 are naturally occurring antioxidant compounds that are also found in human skin. These bioactive compounds have been the focus of considerable research due to their antioxidant, anti-inflammatory, and photoprotective properties. In this review, the current state of the art in the encapsulation of carotenoids and coenzyme Q10 in lipid nanoparticles to improve their bioavailability, chemical stability, and skin absorption is discussed. Additionally, the main findings are highlighted on the cytotoxic and photoprotective effects of these systems in the skin.

A crossover clinical study to evaluate pain intensity from microneedle insertion in different parts of the oral cavity.

The objective of the present study was to evaluate discomfort and safety of microneedle (MN) insertion in several intraoral regions. A device was developed to standardize MN insertions. MNs were inserted in the following regions of the oral cavity: gingiva, palatine alveolar process, buccal mucosa, dorsum of the tongue and inner portion of the lower lip. Perforations from MNs post insertion were confirmed with topical gentian violet stain. Pain was evaluated in a randomized, double-blinded, crossover study in 30 volunteers. Each volunteer received a MN patch, a 30G hypodermic needle (positive control) and an identical MN patch with its needles laying flat in the plane of the patch (negative control). Adverse events were visually evaluated immediately after (0 h) and 24 h post MN application. The application device developed a consistent application force (10 N) and promoted perforation of all individual MNs on a patch. At all sites, insertion of the hypodermic needle promoted more pain when compared to the negative control (p < 0.001). Application of the MNs promoted less pain than the hypodermic needle (p < 0.05), but slightly more pain as compared to the negative control (p < 0.05) at all sites except the tongue, where the MN did not differ from the negative control (p > 0.05). Hypodermic needle caused bleeding at all insertion sites. In contrast, MNs did not cause bleeding at most sites except in some cases of insertion into the hard gingiva and the palatine alveolar process where tiny blood spots appeared immediately after MN application for few of the MNs on the patch. There were no cases of bleeding at 24 h post MN application. In conclusion, MNs can perforate different sites of the oral cavity in a safe and significantly less painful manner as compared to the 30G hypodermic needle. Thus, analogous to the skin, MN-based approaches could be an attractive approach for drug delivery in the oral cavity.

Surgical treatment of ankyloglossia using an ophthalmic topical anesthetic and a tentacannula for tongue elevation: a case report

Ankyloglossia is characterized by the presence of a short lingual frenum that can be inserted from the alveolar ridge to the lingual apex and, until promoting a true fusion of the tongue to the floor. A short lingual frenum can generate several problems such as phonetic disorders. Objective: To describe a surgical technique for the treatment of ankyloglossia using a topical ophthalmic anesthetic and a tentacannula for tongue elevation. Case report: A 15-year-old female was referred for lingual frenulum surgery due to speech impairment. Clinical examination revealed the presence of ankyloglossia which was both hindering the pronunciation of T, D, L phonemes and reducing tongue mobility. The surgical technique chosen was a lingual frenectomy. An ophthalmic topical anesthetic was initially applied to the lateral borders of the frenum with the patient in an upright position and in the presence of adequate aspiration. With the aid of a tentacannula the tongue was raised and the frenulum gradually released with a Goldman-Fox serrated scissor. The topical anesthetic was continuously trickled onto the surgical site during surgery. Results: No postoperative pain was reported by the patient, healing occurred normally and there was no recurrence of abnormal frenulum insertion. Conclusion: The advantages of this technique in comparison to conventional methods which use infiltrative anesthesia include less trauma and a more precise evaluation of tongue movements during surgery, because there will be better control of mobility for the patient when compared to infiltrative techniques.

Introdução: A anquiloglossia caracteriza-se pela presença de um freio lingual curto que pode inserir-se desde o rebordo alveolar até o ápice lingual e, até promover uma verdadeira fusão da língua ao assoalho. Um freio lingual curto poderá gerar vários problemas como distúrbios fonéticos. Objetivo: descrever uma técnica cirúrgica para tratamento da anquiloglossia utilizando um anestésico tópico oftálmico e uma tentacânula para elevação da língua. Relato do caso: Uma paciente com 15 anos de idade foi encaminhada para cirurgia do frênulo lingual devido ao comprometimento da fala. O exame clínico revelou a presença de anquiloglossia, dificultando a pronúncia dos fonemas T, D, L e, reduzindo a mobilidade da língua. A técnica cirúrgica escolhida foi a frenectomia lingual. Um anestésico tópico oftálmico foi aplicado inicialmente nas bordas laterais do freio com o paciente na posição vertical e na presença de aspiração adequada. Com o auxílio de uma tentacânula, a língua foi elevada e o frênulo foi gradualmente liberado com uma tesoura serrilhada Goldman-Fox. O anestésico tópico foi continuamente gotejado para o local cirúrgico durante a cirurgia. Resultados: Nenhuma dor pós-operatória foi relatada pelo paciente, a cicatrização ocorreu normalmente e não houve recorrência da inserção anormal do frênulo. Conclusão: As vantagens dessa técnica em comparação aos métodos convencionais que utilizam anestesia infiltrativa, incluem menor trauma e uma avaliação mais precisa dos movimentos da língua durante a cirurgia, pois haverá um melhor controle da mobilidade do paciente quando comparado às técnicas infiltrativas.

Effectiveness and adverse events of topical and allergen immunotherapy for atopic dermatitis: a systematic review and network meta-analysis protocol.

BACKGROUND: Atopic dermatitis (AD) is an inflammatory chronic condition that affects the skin of children and adults and has an important impact on the quality of life. Treatments for AD are based on environmental controls, topical and systemic therapies, and allergen-specific immunotherapy (AIT). However, it remains unclear the effectiveness and adverse events of AIT and all conventional topical treatments compared with placebo and each other for AD. METHODS: We will search five electronic databases [Central Cochrane register of controlled trials (CENTRAL), MEDLINE, EMBASE, CINAHL, and LILACS] from inception until November 2019 with no language restriction, and we will include experimental studies [randomized controlled trials (RCTs), and quasi-RCTs]. The primary outcome is global and specific skin symptoms assessment. Secondary outcomes are hospital length of stay, quality of life, and adverse events. Reviewers independently will extract data from the studies that meet our inclusion criteria and will assess the risk of bias of individual primary studies. We will conduct random effects pairwise meta-analyses for the observed pairwise comparisons with at least two trials. Then, we will perform random-effects Bayesian network meta-analysis (NMA) to obtain treatment effects for all possible comparisons and to provide a hierarchy of all interventions for each outcome. Possible incoherence between direct and indirect sources of evidence will be investigated locally (if possible) and globally. To investigate sources of statistical heterogeneity, we will perform a series of meta-regression analyses based on pre-specified important effect modifiers. Two authors will appraise the certainty of the evidence for each outcome applying the GRADE's framework for NMA. DISCUSSION: The findings of this systematic review will shed the light on the effectiveness and adverse events of all possible comparisons for treating AD and on the quality of the collated evidence for recommendations. It will also provide critical information to health care professionals to comprehend and manage this disease at different age stages, treatment type, duration, and severity of atopic dermatitis. SYSTEMATIC REVIEW REGISTRATION: PROSPERO Protocol ID CRD42019147106.

Lipid nanoparticles as carriers of cyclodextrin inclusion complexes: A promising approach for cutaneous delivery of a volatile essential oil.

Solid inclusion complexes with cyclodextrins (CD) may be used to overcome volatility and solubility problems of essential oils of pharmacological interest. However, they lack the many dermatological advantages of lipid nanoparticles. This study intends to evaluate the ability of nanostructured lipid carriers (NLC) to encapsulate hydroxypropyl-ß-cyclodextrin inclusion complexes of Lippia origanoides essential oil (EO) and to maintain the desirable aspects of lipid colloids interaction with the skin, specifically follicular accumulation and controlled delivery. CD and NLC were also evaluated separately. Thymol (TML) was used as the essential oil marker and to produce control formulations. As expected, CD alone, though effective in overcoming volatility and low aqueous solubility of TML, were ineffective in controlling marker release (˜50% of EO released after 3 h, Hixson-Crowell kinetics). Even though NLC controlled drug release (˜20% EO released after 12 h, zero-order kinetics) enabling TML penetration into the skin (> 40 µg/cm2after 12 h), NLC alone were not efficient in preventing TML volatility, especially at higher temperatures (calculated shelf-life of 2 days at 35 °C). The combined approach resulted in a synergistic effect (˜20% EO released after 12 h; shelf life of 6 days). The lack of statistical difference of TML skin penetration from NLC and NLC-CD suggests the developed system maintained all skin interaction aspects of lipid colloids, including follicular accumulation forming a depot for controlled delivery. In conclusion, lipid nanoparticles demonstrated to be promising carriers for inclusion complexes of this particular volatile essential oil.

PnPP-19 Peptide Restores Erectile Function in Hypertensive and Diabetic Animals Through Intravenous and Topical Administration.

INTRODUCTION: With the aim of overcoming the high toxicity of PnTx2-6 (or δ-CNTX-Pn2a), a toxin from the venom of the armed spider (Phoneutria nigriventer), the 19-aminoacid peptide, PnPP-19 (P nigriventer potentiator peptide), was synthesized based on molecular modeling studies of PnTx2-6. PnPP-19 improved the erectile function of normotensive rats and mice, without eliciting side effects, and no signs of toxicity were observed. In addition, PnPP-19 was able to potentiate the effect of sildenafil. AIM: To evaluate the efficacy of PnPP-19 in hypertensive and diabetic mouse/rat models in restoring erectile function, after topical administration; verify the biodistribution of PnPP-19 administration (topical and intravenous), permeation, and cyclic guanosine monophosphate (cGMP)/nitric oxide via implication. METHODS: Corpus cavernosum relaxation was evaluated using cavernous strips from male spontaneous hypertensive rats (SHR) and from streptozotocin (STZ)-diabetic mice contracted with phenylephrine and submitted to electrical field stimulation before and after incubation with PnPP-19 (10-8 mol/L, 10 minutes) or vehicle. This procedure was also used to determine cGMP/nitric oxide levels, at 8 Hz and to check the effect of PnPP-19 with sildenafil citrate. Biodistribution assays were performed using iodine 123-radiolabeled PnPP-19. In vivo erectile function was evaluated using intracavernosal pressure/main arterial pressure ratio in STZ-diabetic rats after PnPP-19 topical administration. MAIN OUTCOME MEASURES: PnPP-19 may become a new drug able to fill the gap in the pharmacologic treatment of erectile dysfunction, especially for hypertensive and diabetic individuals RESULTS: PnPP-19 potentiated corpus cavernosum relaxation, in both control and SHR rats. SHR-cavernosal tissue treated with PnPP-19 (1-32 Hz) reached the same relaxation levels as control Wistar rats (16 and 32 Hz). PnPP-19 treatment improved cavernosal tissue relaxation in STZ-diabetic mice and rats. PnPP-19 enhanced cGMP levels in STZ-diabetic mice corpus cavernosum strips. After topical or intravenous administration in rats, 123I-PnPP-19 was mainly recruited to the penis. When topically administered (400 µg/rat), PnPP-19 restores erectile function in STZ-diabetic rats, also improving it in healthy rats by increasing the intracavernosal pressure/main arterial pressure ratio. PnPP-19 exhibited an additive effect when co-administered with sildenafil, showing a novel mode of action regardless of phosphodiesterase type 5 inhibition. CLINICAL IMPLICATIONS: PnPP-19 seems to be an indicated drug to be tested to treat ED in diabetic and hypertensive patients. STRENGTH & LIMITATIONS: PnPP-19, although active by topical application and showing safety to human beings (not shown), has low permeability, about 10% of the applied dose. CONCLUSION: Our results showed that PnPP-19 may emerge as a potent new drug that can be topically administered, becoming a promising alternative for erectile dysfunction treatment. Nunes da Silva C, Pedrosa Nunes K, De Marco Almeida F, et al. PnPP-19 Peptide Restores Erectile Function In Hypertensive And Diabetic Animals Through Intravenous And Topical Administration. J Sex Med 2019;16:365-374.

Evaluación de formulaciones de ketoconazol para uso tópico en leishmaniasis cutánea por Leishmania(Viannia) / Evaluation of ketoconazole formulations for topical use in cutaneous leishmaniasis caused by Leishmania (Viannia)

RESUMEN Se evaluó la efectividad de diversas formulaciones farmacéuticas de ketoconazol en modelos experimentales de leishmaniasis cutánea (LC) en ratones BALB C. Fueron preparadas formulaciones tópicas tipo gel, lipogel y crema conteniendo potenciadores de la permeación y diferentes concentraciones de ketoconazol. Se determinó la estabilidad, la toxicidad y la actividad anti-Leishmania in vitro. Además, se evaluó in vivo la efectividad de las formulaciones aplicadas tópicamente en ratones con LC infectados con Leishmania (Viannia) braziliensis. Las formulaciones tipo crema fueron evaluadas adicionalmente en ratones infectados con L. (V.) panamensis. Los sistemas evaluados mantuvieron in vitro la actividad del ketoconazol contra los parásitos; sin embargo, ninguna de las formulaciones fue efectiva en curar las lesiones de LC en los ratones. El tratamiento tópico con miltefosina (utilizado como control) curó las lesiones. Se concluye que las formulaciones que contienen ketoconazol diseñados en este estudio, no fueron efectivos contra la LC en los ratones infectados.

ABSTRACT The effectiveness of various pharmaceutical formulations of ketoconazole was evaluated in experimental models of cutaneous leishmaniasis (LC) in BALB C mice. Topical gel, lipogel, and cream formulations containing permeation enhancers and different concentrations of ketoconazole were prepared. Stability, toxicity and anti-Leishmania activity were determined in vitro. In addition, the effectiveness of topically applied formulations in LC-infected mice infected with Leishmania (Viannia) braziliensis was evaluated in vivo. Cream formulations were additionally evaluated in mice infected with L. (V.) panamensis. The systems evaluated maintained in vitro the activity of ketoconazole against parasites; however, none of the formulations were effective in curing LC lesions in mice. Topical treatment with miltefosine (used as a control) cured the lesions. It is concluded that the ketoconazole-containing formulations designed in this study were not effective against LC in infected mice.

Copaiba oil enhances in vitro/in vivo cutaneous permeability and in vivo anti-inflammatory effect of celecoxib.

OBJECTIVES: The aim of this article was to use copaiba oil (C.O) to improve skin permeability and topical anti-inflammatory activity of celecoxib (Cxb). METHODS: Formulations containing C.O (1-50%) were associated with Cxb (2%). In vitro skin permeability studies were conducted using porcine ear skin. Histological analysis of the hairless mice skin samples after application of formulations was achieved with the routine haematoxylin/eosin technique. The anti-inflammatory activity was assessed using the AA-induced ear oedema mice model. KEY FINDINGS: The formulation containing 25% C.O promoted the highest levels of in vitro Cxb permeation through pig ear skin, retention in the stratum corneum (SC) and epidermis/dermis of pig ear skin in vitro (~5-fold) and hairless mice skin in vivo (~2.0-fold), as compared with the control formulation. At 25%, C.O caused SC disorganization and increased cell infiltration and induced angiogenesis without clear signs of skin irritation. The formulation added to 25% C.O as adjuvant inhibited ear oedema and protein extravasation by 77.51 and 89.7%, respectively, and that it was, respectively, 2.0- and 3.4-fold more efficient than the commercial diethylammonium diclofenac cream gel to suppress these inflammatory parameters. CONCLUSIONS: 25% C.O is a potential penetration enhancer for lipophilic drugs like Cxb that can improve cutaneous drug penetration and its anti-inflammatory activity.

A simple HPLC method for the determination of halcinonide in lipid nanoparticles: development, validation, encapsulation efficiency, and in vitro drug permeation

ABSTRACT Halcinonide is a high-potency topical glucocorticoid used for skin inflammation treatments that presents toxic systemic effects. A simple and quick analytical method to quantify the amount of halcinonide encapsulated into lipid nanoparticles, such as polymeric lipid-core nanoparticles and solid lipid nanoparticles, was developed and validated regarding the drug's encapsulation efficiency and in vitro permeation. The development and validation of the analytical method were carried out using the high performance liquid chromatography with the UV detection at 239 nm. The validation parameters were specificity, linearity, precision and accuracy, limits of detection and quantitation, and robustness. The method presented an isocratic flow rate of 1.0 mL.min-1, a mobile phase methanol:water (85:15 v/v), and a retention time of 4.21 min. The method was validated according to international and national regulations. The halcinonide encapsulation efficiency in nanoparticles was greater than 99% and the in vitro drug permeation study showed that less than 9% of the drug permeated through the membrane, indicating a nanoparticle reservoir effect, which can reduce the halcinonide's toxic systemic effects. These studies demonstrated the applicability of the developed and validated analytical method to quantify halcinonide in lipid nanoparticles.

[From evidence to expertise: concordance in the topical management of psoriasis]. / De la evidencia a la experiencia: concordancia en el manejo tópico de la psoriasis.

Vulgar psoriasis is an inflammatory cutaneous-systemic disease, chronic and intermittent. Its etiology is not defined, and it has a higher risk of comorbidities which affect the patients' quality of life. The objectives of this trial were establishing the concordance between Guía de Práctica Clínica (GPC) of the plaque psoriasis pharmacological treatment and the clinical practice of a group of Mexican dermatologists, experts in the psoriasis topical treatment; as well as weighing up the interest and knowledge of quality of life and adherence to treatment. A Delphi questionnaire was applied to 30 experts to explore their therapeutic behavior and attitudes toward the assessment of quality of life and treatment adherence. A meeting was held with a subgroup of 10 dermatologists to analyze the results. A second questionnaire was responded to distinguish the decisions taken for topical treatment in institutional and private practice, as well as other items unexplored in the first questionnaire. After analyzing the questionnaires results, it was clear that the data published in the Guía de Práctica Clínica and the prescriptive attitude of the experts are consistent with respect to the topical treatment for plaque psoriasis. There is also agreement on the attitude about drug prescriptions between the physicians in the private and institutional medical care, although in the private practice it is more common to use vitamin D analogues and corticosteroids and the salicylic acid replaces corticosteroids in the institutions.

La psoriasis vulgar es una enfermedad inflamatoria cutáneo-sistémica, de evolución crónica e intermitente, sin etiología definida y con mayor riesgo de comorbilidades que afectan la calidad de vida de los pacientes. Los objetivos del estudio fueron conocer la concordancia entre las guías de práctica clínica (GPC) del tratamiento farmacológico de la psoriasis en placas y la práctica clínica de un grupo de dermatólogos mexicanos expertos en el tratamiento tópico de la psoriasis, así como ponderar el interés y el conocimiento de la calidad de vida y el apego a tratamiento. Se aplicó un cuestionario Delphi a 30 expertos para explorar su conducta terapéutica tópica y las actitudes hacia la evaluación de la calidad de vida y el apego al tratamiento. Se realizó una reunión con un subgrupo de 10 dermatólogos para analizar los resultados. En una reunión se contestó un segundo cuestionario y se resolvieron las discrepancias para la toma de decisiones en tratamiento tópico en los ámbitos privado e institucional, así como algunos otros temas no explorados en la primera etapa. Al analizar los resultados de las encuestas, se encontró que existe concordancia entre lo publicado en la GPC y la conducta prescriptiva de los expertos en lo referente al tratamiento tópico de la psoriasis en placas. En cuanto a la conducta de prescripción entre la práctica privada y la institucional se encontraron puntos de coincidencia, excepto que en la primera se prefiere utilizar análogos de vitamina D y corticosteroides, mientras que en la segunda, el ácido salicílico sustituye a los corticosteroides.