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Obesity, characterized by excessive storage of lipids, has become a global pandemic with high incidence levels, and its forecast is not encouraging. Currently, there are different strategies to treat obesity; however, these conventional methods have various limitations. Lifestyle changes may result in poor outcomes due to the complexity of obesity causes, pharmaceutic treatments produce severe side effects, and bariatric surgery is highly invasive. In the search for alternative treatments to fight obesity, transdermal drug delivery systems of anti-obesogenic molecules have gained particular attention. However, the diffusion of molecules through the skin is the main drawback due to the characteristics of different layers of the skin, principally the stratum corneum and its barrier-like behavior. In this sense, microneedles patches (MP) have emerged to overcome this limitation by piercing the skin and allowing drug delivery inside the body. Although MP have been studied for some years, it was not until about 2017 that their potential as anti-obesogenic treatment was reported. This article aims to summarize and analyze the strategies employed to produce MP and to embed the active molecules against obesity. Special attention is focused on the microneedle's material, geometry, array, and additional delivery strategies, like nanoencapsulation. MP are a promising tool to develop an easy-access treatment, avoiding the digestive tract and with the capacity to enhance the anti-obesogenic activity by delivering one or more active molecules.

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Female Pattern Hair Loss (FPHL) is a common form of non-scaring hair loss that occurs in adult women. Although several treatments have already been proposed for FPHL, only Topical Minoxidil accumulated an adequate level of evidence. This study aimed to evaluate the therapeutic response of MMP® (intradermal infiltration) of Minoxidil formulation in the frontal-parietal-vertex regions compared with the gold-standard home administration of Minoxidil 5% Capillary Solution. This self-controlled comparative study evaluated 16 FPHL patients, without treatment for at least 6 months, confirmed by trichoscopy with TrichoLAB® software. They received 4 monthly sessions of MMP® with Minoxidil 0,5% on the right side of the scalp (frontal-parietal-vertex areas), followed by occlusion with plastic film for 12 h and prescription of Minoxidil 5% Solution for home use once a day, on both scalp sides, starting 72 h after the procedure. The reassessment trichoscopy was 6 weeks after the last session and they answered a "self-assessment" questionnaire. Treated scalp areas were compared and showed both treatments, in general, were effective, with no difference between them. If they were analyzed separately by treated areas, there were signs of better response in the parietal-vertex regions with treatment by MMP® with Minoxidil, while clinical treatment indicated a better response in the other regions. When patients were divided into more and less advanced cases, a better response in parietal-vertex regions treated by MMP® with Minoxidil in less advanced patients was confirmed. MMP® with Minoxidil showed a better response in the parietal-vertex regions in less advanced FPHL patients. It represents yet another resource to improve quality of life of these suffering patients.

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Both intrinsic and extrinsic aging lead to a series of morphological changes in the skin including the flattening of the dermal-epidermal junction, increased stratum corneum dryness, reduction in sebaceous gland activity and enzyme activity as well as atrophy of blood vessels. In this study, the impact of these changes on the transport of molecules through the skin was revised. The increase in the number of transdermal formulations on the market in recent decades and life expectancy represent the main reasons for an in-depth discussion of this topic. Furthermore, elderly subjects have often been excluded from clinical trials due to polypharmacy, raising concerns in terms of efficacy and safety. In this way, ex vivo and in vivo studies comparing the transport of molecules through the mature and young skin were analyzed in detail. The reduced water content in mature skin had a significant impact on the transport rate of hydrophilic molecules. The lower enzymatic activity in aged skin, in turn, would explain changes in the activation of prodrugs. Interestingly, greater deposition of nanoparticles was also found in mature skin. In vivo models should be prioritized in future experimental studies as they allow to evaluate both absorption and metabolism simultaneously, providing more realistic information.

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OBJECTIVE: This systematic literature review aims to evaluate the effectiveness of transdermal opioids in managing cancer pain and their impact on the quality of life (QoL) of patients. DATA SOURCES: A systematic literature review conducted following the PRISMA protocol, focusing on randomized clinical trials found in the Lilacs, Embase, PubMed, and SciELO databases over the last 20 years. STUDY SELECTION AND DATA EXTRACTION: We included randomized clinical trials, published in English, Portuguese, or Spanish, which assessed the impact of transdermal opioids on the QoL. Data extraction was facilitated using the Rayyan app. DATA SYNTHESIS: Six articles meeting the inclusion and exclusion criteria were analyzed. These studies covered a population ranging from 24 to 422 cancer patients experiencing moderate to severe pain. The risk of bias was assessed in each study, generally being categorized as uncertain or high. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: The findings indicate that the analgesic effectiveness and side effects of transdermal formulations (specifically buprenorphine and fentanyl) for managing moderate to severe cancer pain are comparable to, or in some cases superior to, those of oral opioids traditionally employed. CONCLUSIONS: Transdermal therapy was suggested to have several advantages over oral opioid therapy in enhancing cancer patients' QoL. These benefits span various dimensions, including pain management, physical functioning, mental health, vitality, overall patient improvement, anger/aversion, strength/activity, general QoL, cognitive and emotional functions, fatigue, and insomnia.

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BACKGROUND: Two classes of medications are used to treat Alzheimer's disease (AD); donepezil, galantamine, and rivastigmine are acetylcholinesterase inhibitors, and memantine is a non-competitive antagonist of the N-methyl-D-aspartate receptor. Although these are typically taken orally, there are transdermal therapeutic systems (TTSs) commercially available for rivastigmine and donepezil. The transdermal route has been preferable for guardians/caregivers due to ease of use, reduced side effects, and improved adherence to therapy. OBJECTIVE: The study aimed to obtain knowledge of the properties of these drugs and to search for patents relating to the TTS for AD using the Espacenet platform. METHODS: The search terms were "rivastigmine AND transdermal AND skin delivery AND Alzheimer's", changing the drugs "memantine", "donepezil", and "galantamine", between January 2015 and January 2022. Title and abstract were used to choose patents. RESULTS: TTSs present some limit factors in terms of absorption due to skin physiology and the size of the molecules with established limits of percutaneous penetration (molecular mass of 500 g/mol and log P of 5). We found 1, 4, 4, and 2 patents for galantamine, rivastigmine, donepezil, and memantine, respectively. Galantamine TTS seems to be more challenging due to the molecular mass of 287.35 g/mol and logP of 1.8. The permeator of absorption is necessary. Memantine, rivastigmine, and donepezil present logP of 3.28, 2.3, and 4.27 and molecular weights of 179.30, 250.34, and 415.96 g/mol, respectively. CONCLUSION: TTSs are primarily effective for delivering small molecules. The use of absorption enhancers and irritation mitigators can be necessary to enhance the performance. The development of these technologies is essential for the convenience of patients and caregivers.

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Systemic photobiomodulation (PBM) of the blood or over blood vessels has been associated with bio-stimulating, vasodilating, and anti-inflammatory properties. This treatment modality has been used for modulating inflammatory processes, tissue repair, atherosclerosis, and systemic arterial hypertension, and is described more often in clinical studies than experimental models. Therefore, the aim of the present study was to conduct a literature review regarding the effect of systemic PBM involving the intravascular laser irradiation of blood (ILIB) or non-invasive vascular photobiomodulation (VPBM) using low-level laser (LLL) in experimental (animal) models. The PubMed/MEDLINE®, Scopus, SPIE Digital Library, and Web of Science databases were searched for articles on the use of VPBM with LLL in animal models. Nine original articles met the inclusion criteria and were critically evaluated. The variables of interest were the dosimetric laser parameters, different methods for delivering energy, and the main results. The use laser in the red spectrum was more prevalent and VPBM (non-invasive) predominated over ILIB (invasive). No standardization was found in the dosimetric parameters. However, the studies showed the positive effects of VPBM on arterial pressure and blood circulation, the positive effects of ILIB on blood composition and hematological markers, as well as positive effects of both forms of systemic PBM (ILIB and VPBM) on the tissue repair process. In conclusion, the studies evaluated in the present review showed that the use of systemic PBM with ILIB or non-invasive VPBM induced positive effects, modulating metabolic conditions and tissue repair. However, there is a need for standardization in the dosimetric parameters for the different conditions and processes evaluated using experimental models.

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Testosterone (T) regulates immune function, with both immunostimulatory and immunosuppressive effects on several vertebrates. We investigated the covariation between plasma T and corticosterone (CORT) levels and immunity (plasma bacterial killing ability (BKA), and neutrophil to lymphocyte ratio (NLR)) in free-living Rhinella icterica male toads inside and outside the reproductive season. We found an overall positive correlation between steroids and immune traits, with toads during the reproductive season displaying increased T, CORT and BKA. We also investigated the T transdermal application effects on T, CORT, phagocytosis of blood cells, BKA and NLR in captive toads. Toads were treated with T (1, 10 or 100 µg) or vehicle (sesame oil) for eight consecutive days. Animals were bled on the first and eighth days of treatment. Increased plasma T was observed on the first and last day of T-treatment, while increased BKA was observed following all T doses on the last day, with a positive correlation between T and BKA. Plasma CORT, NLR and phagocytosis increased on the last day for all T-treated and vehicle groups. Overall, we demonstrated a positive covariation between T and immune traits in the field and T-induced augmented BKA in captive toads, indicating a T immunoenhancing effect in R. icterica males. This article is part of the theme issue 'Amphibian immunity: stress, disease and ecoimmunology'.

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ABSTRACT BACKGROUND AND OBJECTIVES: Neuropathic pain is defined as a pain caused by a lesion or condition that affects the somatosensory nervous system. Taking its prevalence into account, in particular post-traumatic localized neuropathic pain, and to discuss ways to manage patients with this condition, considering efficacy and tolerability of proposed treatments, this report presents three clinical cases of patients with post-traumatic localized neuropathic pain treated with 5% lidocaine transdermal patch in both monotherapy and polytherapy. CASE REPORTS: This study reports the cases of three female patients aged between 29 and 81 years with complaints of pain due to trauma, who were managed with 5% lidocaine transdermal patch in prolonged treatment, with a significant improvement in pain. CONCLUSION: According to scientific evidence, the use of 5% lidocaine transdermal patch in post-traumatic localized neuropathic pain as shown efficacy with favorable safety and tolerance. Moreover, it was possible to demonstrate that a 5% lidocaine transdermal patch in a polytherapy format has contributed to improved outcomes with no effect in treatment tolerability.

RESUMO JUSTIFICATIVA E OBJETIVOS: A dor neuropática é definida como uma dor provocada por uma lesão ou doença que afeta o sistema nervoso somatossensitivo. Considerando a sua prevalência, em particular dor neuropática localizada pós-traumática, com o intuito de discutir formas de manejar os pacientes portadores dessa condição e avaliando tanto a eficácia quanto a tolerabilidade aos tratamentos propostos, este artigo apresenta três casos clínicos de pacientes portadores dessa condição, tratados com emplastro de lidocaína a 5%, tanto em monoterapia quanto no contexto da terapia multimodal. RELATOS DOS CASOS: Este estudo relata três casos de pacientes do sexo feminino com idades entre 29 e 81 anos e queixas de dor decorrente de trauma, que foram manejadas com emplastro de lidocaína a 5% em tratamento prolongado, com uma significativa melhora do nível de dor. CONCLUSÃO: Em concordância com as evidências da literatura científica, o uso do emplastro de lidocaína a 5% nos casos de dor neuropática localizada pós-traumática relatados mostrou-se eficaz no manejo dessa condição e apresentou perfil de segurança e tolerabilidade favorável. Além disso, foi possível observar também que o emplastro de lidocaína a 5%, quando adicionado em abordagem multimodal, contribuiu para uma melhora no quadro sem prejuízo da tolerabilidade do tratamento.

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INTRODUCTION: The skin is an attractive route for drug delivery. However, the stratum corneum is a critical limiting barrier for drug permeation. Nanoentrapment is a way to enhance cutaneous drug delivery, by diverse mechanisms, with a notable trend of nanoparticles accumulating into the hair follicles when topically applied. Iontophoresis is yet another way of increasing drug transport by applying a mild electrical field that preferentially passes through the hair follicles, for being the pathway of lower resistance. So, iontophoresis application to nanocarriers could further increase actives accumulation into the hair follicles, impacting cutaneous drug delivery. AREAS COVERED: In this review, the authors aimed to discuss the main factors impacting iontophoretic skin transport when combining nanocarriers with iontophoresis. We further provide an overview of the conditions in which this combination has been studied, the characteristics of nanosystems employed, and hypothesize why the association has succeeded or failed to enhance drug permeation. EXPERT OPINION: Nanocarriers and iontophoresis association can be promising to enhance cutaneous drug delivery. For better results, the electroosmotic contribution to the iontophoretic transport, mainly of negatively charged nanocarriers, charge density, formulation pH, and skin models should be considered. Moreover, the transfollicular pathway should be considered, especially when designing the nanocarriers.

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Scalp microinfusion is a promising novel drug delivery technique for hair loss treatment. We discuss the MMP® technique and review its possible use in alopecias. MMP® technique provides a small amount of drugs delivered homogeneously into the skin combined with micro-needling and can, therefore, provide optimal delivery. However, literature on this technique is limited to a few case reports despite its wide use in some countries. Further studies are needed to standardize protocols.

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BACKGROUND: Transdermal drug delivery has contributed positively to medical practice. However, prescriptions that do not meet minimum quality criteria and medication errors are common. OBJECTIVE: The objective was to determine how transdermal patches are being prescribed to a group of patients in Colombia, the compliance with established requirements of such prescriptions and the comparisons between correct and incorrect prescriptions. METHODS: This was a cross-sectional study of prescriptions for transdermal patches using data from a population-based drug dispensing database between December 1 and 31, 2019. Medical prescriptions were randomly reviewed, establishing whether the drugs were appropriately prescribed by the manufacturer's indications or national regulations. Descriptive and bivariate analysis was performed. RESULTS: A total of 415 prescriptions were reviewed; the prescription was provided to 412 patients with a median age of 76.9 years, and 63.3% were women. Rivastigmine was the most prescribed transdermal patch (57.8%). 66.3% of all prescriptions did not meet the minimum appropriate prescribing standards, especially those for rivastigmine (97.1%). The 7.0% of all prescriptions had posology errors, especially prescriptions for buprenorphine (43.8%). Older patients (84.4% vs 52.5%), from the Pacific region (34.4% vs 23.7%), with manual formulations (22.1% vs 0.8%), dementia (49.0% vs 6.8%), and in management with lipid-lowering drugs (41.8% vs 30.5%), presented incorrect transdermal patch formulations more frequently (p < 0.05). CONCLUSION: The high proportion of inappropriately prescribed transdermal patches should draw the attention of those responsible for health care to improve the training of physicians and create prescription quality verification systems.

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INTRODUCCIÓN: La anticoncepción es un derecho, y es obligación del Estado garantizar el acceso a métodos anticonceptivos efectivos, seguros y de calidad. Se realizó una evaluación de tecnología sanitaria sobre los parches anticonceptivos transdérmicos. MÉTODOS: Un equipo multidisciplinario e independiente designado por el Comité Provincial de Biotecnologías de Neuquén buscó información epidemiológica, regulatoria y evidencias científicas sobre eficacia, seguridad y adherencia. Se analizó y sistematizó siguiendo metodología GRADE (Grading of Recommendations Assessment, Development and Evaluation) y CASPe (Critical Appraisal Skills Programme Español). RESULTADOS: El único parche autorizado en Argentina para su comercialización libera 33,9 µg/día de etinilestradiol y 203 µg/día de norelgestromina. Su prospecto en Argentina, EE.UU. y Europa lo asocia al doble de riesgo de enfermedad tromboembólica venosa si se compara con las píldoras anticonceptivas que provee el Estado. Esto coincide con resultados de estudios de cohortes de alta calidad. Los parches proveen similar eficacia anticonceptiva a corto plazo, pero con altas tasas de abandono en el seguimiento. La Organización Mundial de la Salud no los ha incluido en su listado de medicamentos esenciales. Los parches son más costosos que otros métodos disponibles. DISCUSIÓN: Sobre la base de los principios de beneficencia, no maleficencia, de precaución y de proporcionalidad, no se recomienda la incorporación de parches.(AU)

INTRODUCTION: Contraception is a right, being an obligation of the State to guarantee access to effective, safe and quality contraceptive methods. A health technology assessment was carried out on transdermal contraceptive patches. METHODS: A multidisciplinary and independent team appointed by the Provincial Biotechnology Committee of Neuquén searched for epidemiological and regulatory information and scientific evidence on efficacy, safety and adherence. It was analyzed and systematized following the GRADE (Grading of Recommendations Assessment, Development and Evaluation) and CASPe (Critical Appraisal Skills Programme Español) methodology. RESULTS: The only patch authorized for commercialization in Argentina releases 33.9 µg/day of ethinylestradiol and 203 µg/day of norelgestromin. Its package insert in Argentina, the US and Europe highlights that the risk of venous thromboembolic disease is twice as high compared to the contraceptive pills provided by the State. This is consistent with results from high-quality cohort studies. Patches provide similar short-term contraceptive efficacy, but with high dropout rates at follow-up. The World Health Organization has not included them in its list of essential medicines. Patches are more expensive than other available methods. DISCUSSION: Based on the principles of beneficence, non-maleficence, precaution and proportionality, the incorporation of patches is not recommended.(AU)

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

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ABSTRACT BACKGROUND AND OBJECTIVES: Post-surgical neuropathic pain (NP) is an important clinic condition, with recurring pain and that may be a result of transection, contusion, nerve inflammation or stretching and lasting for 3-6 months. Having into consideration the prevalence of postoperative localized NP, its impact in quality of life of patients, its complexity of diagnosis and treatment and available treatment options, the aim of this report was to present efficacy, safety and tolerability outcomes of 5% lidocaine transdermal patch use as a single treatment or in combination with other therapeutic options by describing and analyzing four clinical cases. CASES REPORT: Four patients aged between 43 and 70 years old and complains of postoperative localized NP were managed with 5% lidocaine transdermal patch in prolonged treatment, with significant improvement in pain scores. CONCLUSION: The outcomes of the described cases revealed that postoperative localized NP management was successful with 5% lidocaine transdermal patch. Moreover, it was possible to observe that its association to other treatments (pharmacological or not) has proved efficacy with no negative impact the tolerability of the treatment or the patient routine and comfort.

RESUMO JUSTIFICATIVA E OBJETIVOS: A dor neuropática (DN) pós-operatória é um problema clínico relevante, com dor persistente, que pode ser resultado de transecção, contusão, alongamento ou inflamação do nervo, durando geralmente cerca de 3-6 meses após a cirurgia. Tendo em consideração a prevalência estimada da DN localizada pós-operatória, seu impacto na qualidade de vida dos pacientes, sua complexidade diagnóstica e terapêutica, e as opções de tratamento disponíveis, o presente estudo teve como objetivo apresentar os desfechos de eficácia, segurança e tolerabilidade do uso do emplastro de lidocaína a 5% nesta condição clínica, seja como fármaco isolado ou em combinação com outras classes terapêuticas. RELATO DOS CASOS: Quatro pacientes com idades entre 43 e 70 anos e com história de DN localizada pós-operatória foram manejados com emplastro de lidocaína a 5% em tratamento prolongado, com melhora significativa do nível de dor. CONCLUSÃO: Os resultados dos casos apresentados neste estudo revelam que o manejo da DN localizada pós-operatória foi eficaz com a utilização do emplastro de lidocaína a 5%. Além disso, foi possível observar que sua associação com outros tratamentos (farmacológicos ou não) mostrou-se efetiva, sem impactar negativamente a tolerabilidade do tratamento ou o conforto do paciente.

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BACKGROUND: Nanoparticle formulations development for anti-aging treatment is increasing due to their multifunctional properties. These nanotechnological strategies can target cellular/ molecular pathways of the skin affected by the aging process. However, a review of these strategies is required to discuss their efficacy/safety and establish the needs for further research. OBJECTIVE: Innovative nanotechnological advances for skin anti-aging/rejuvenation are summarized and discussed in this work. METHODS: The information in this review was extracted from recent and relevant studies using nanotechnology for anti-aging treatment from scientific databases. RESULTS AND DISCUSSION: Results show an enhanced skin anti-aging effect of actives-loaded nanoparticles of next generation (nanostructured lipid carriers, fullerenes, transfersomes, protransfersomes, niosomes, ethosomes, transethosomes, glycerosomes, phytosomes) compared with nanocarriers of first generation or conventional formulations. Anti-aging active ingredients such as, flavonoids (rutin, hesperidin, quercetagetine, quercetin, epigallocatechin-3-gallate, myricetin, silibinin, curcuminoids, isoflavones); vitamins (E, D₃, CoQ10); acids (hyaluronic, ascorbic, rosmarinic, gallic); extracts (Citrus sinensis, Tagetes erecta L., Achillea millefolium L., Citrus aurantium L., Glycyrrhiza glabra L., Aloe vera, propolis earned by Apis mellifera); and other compounds (adenosine, beta-glucan, heptapetide DEETGEF, resveratrol, cycloastragenol, melatonin, botulinum toxin, grapeseed oil), have been successfully entrapped into nanoparticles for skin rejuvenation. This encapsulation has improved their solubility, bioavailability, stability, permeability, and effectivity for skin anti-aging, providing a controlled drug release with minimized side effects. CONCLUSION: Recent studies show a trend of anti-aging herbal active ingredients-loaded nanoparticles, enhancing the moisturizing, antioxidant, regenerating and photoprotective activity of the skin. Suitable safety/shelf-life stability of these novel formulations is key to a successful translation to the clinic/industry.

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Abstract Methotrexate on its oral and intravenous administration results in unwanted adverse effects. This drawback can be overcome by transdermal delivery because of its painless objective for systemic drug administration. Transfersomes are ultra-deformable vesicles with the flexibility to reach deeper tissues of the skin. The objective of this research work was to develop methotrexate transfersomal gel by thin film hydration technique, evaluated for entrapment efficiency, deformability, mean vesicle size, and stability, and incorporated into carbopol gel for ease of handling and skin applicability for a longer period of retention on skin. MTX-TFS gel & conventional gel were characterized for consistency, transparency, viscosity, and pH. Ex-vivo skin permeation studies were performed using abdominal goat skin and drug release kinetic parameters and transdermal flux were calculated using mathematical models. The results indicate that MTX was successfully entrapped (84.77 ± 2.35 %w/w) in transfersomes having 240±1.6 nm vesicle sizes and 27.13±0.7 deformability index. The gel was permeated through the skin at a rate of 28.12±2.58 µg/cm2/hr as compared to the conventional gel (10.35±2.14 µg/cm2/ hr). From the study, it was concluded that the MTX-TFS gel can be used as a possible substitute for the conventional formulation for transdermal drug delivery due to 3 times improvement in transdermal flux.

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Diabetes mellitus is an endocrine disorder that affects glucose metabolism, making the body unable to effectively use the insulin it produces. Transdermal drug delivery (TDD) has attracted strong interest from researchers, as it allows minimally invasive and painless insulin administration, showing advantages over conventional delivery methods. Systems composed of microneedles (MNs) assembled in a transdermal patch provide a unique route of administration, which is innovative with promising results. This paper presents the design of a transdermal patch composed of 25 microneedles manufactured with 3D printing by stereolithography with a class 1 biocompatible resin and a printing angle of 0°. Finite element analysis with ANSYS software is used to obtain the mechanical behavior of the microneedle (MN). The values obtained through the analysis were: a Von Misses stress of 18.057 MPa, a maximum deformation of 2.179×10-3, and a safety factor of 4. Following this, through a flow simulation, we find that a pressure of 1.084 Pa and a fluid velocity of 4.800 ms were necessary to ensure a volumetric flow magnitude of 4.447×10-5cm3s. Furthermore, the parameters found in this work are of great importance for the future implementation of a transdermal drug delivery device.

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Os ruminantes, como todos os animais, têm capacidade de sentir dor, a qual pode ser causada por doenças ou procedimentos frequentemente praticados, como a descorna e a orquiectomia. Todavia, nesses animais, o uso de analgésicos ainda é menos comum do que o ideal, sendo necessária uma maior conscientização, além de estudos com fármacos e protocolos, capazes de aliviar a dor de maneira eficaz nessas espécies. Neste contexto, destacam-se os opioides, potentes fármacos analgésicos, sendo ótima opção para o controle da dor; entretanto, seu uso ainda é pouco frequente em ruminantes, os estudos são limitados e encontram resultados variáveis. Diante disso, o objetivo deste trabalho foi revisar os benefícios do controle da dor em ruminantes, através do uso de opioides, elucidando as possibilidades analgésicas com diferentes fármacos desta classe e vias de administração, a fim de incentivar o uso pelos médicos veterinários de ruminantes, com base na literatura já publicada sobre este assunto; uma vez que, mesmo com alguns resultados variáveis, diversos estudos têm demonstrado o potencial antinociceptivo dos opioides em ruminantes, além dos efeitos sedativos, destacando o potencial analgésico principalmente por vias de administração alternativas, como o fentanil transdérmico e a via epidural para diversos opioides, os quais tornam-se opções importantes a serem consideradas nos protocolos analgésicos para ruminantes.

Ruminants, as all other animals, feel pain, which can be caused by diseases or frequently practiced procedures, such as dehorning and orchiectomy. However, in these animals the use of analgesics is still less common than ideal, requiring greater awareness, in addition to studies with drugs and protocols capable of effectively relieving pain in these species. In this context, opioids, potent analgesic drugs, are highlighted as a great option for pain control. Nevertheless, their use is still infrequent in ruminants, where studies are limited and show varied results. Therefore, the objective of this study was to review the benefits of pain control in ruminants through opioids, elucidating the analgesic possibilities with different drugs of this class and administration routes to encourage the use by veterinarians of ruminants, based on the literature already published on this subject. Even with some variable results, several studies have demonstrated the antinociceptive potential of opioids in ruminants, in addition to the sedative effects, highlighting the analgesic potential mainly through alternative routes of administration, such as transdermal fentanyl and the epidural route for various opioids, which become important options to be considered in analgesic protocols for ruminants.

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Transdermal administration of molecules across the skin has gained interest because it can be considered a non-invasive route compared with traditional ones. However, going through the skin is challenging due to the presence of the stratum corneum, the main barrier of substances. For this reason, the goal of this research was the combination of omega-3 (ω-3) and a dextran sulfate assembly in a nanostructure form, which allows passage through the skin and improves the bioavailability and the therapeutic profiles of active molecules, such as imiquimod. Here we report a new colloidal system, named dextran nanocapsules, with ω-3 in its nucleus and a coat made of dextran sulfate with a size ~150 nm, monomodal distribution, and negative zeta potential (~-33 mV). This nanosystem encapsulates imiquimod with high efficacy (~86%) and can release it in a controlled fashion following Korsmeyer-Peppas kinetics. This formulation is stable under storage and physiological conditions. Furthermore, a freeze-dried product could be produced with different cryoprotectants and presents a good security profile in the HaCaT cell line. Ex vivo assays with newborn pig skin showed that dextran nanocapsules promote transdermal delivery and retention 10 times higher than non-encapsulated imiquimod. These promising results make this nanosystem an efficient vehicle for imiquimod transdermal delivery.

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This article presents microneedles analyses where the design parameters studied included length and inner and outer diameter ranges. A mathematical model was also used to generalize outer and inner diameter ratios in the obtained ranges. Following this, the range of inner and outer diameters was completed by mechanical simulations, ranging from 30 µm to 134 µm as the inner diameter range and 208 µm to 250 µm as the outer diameter range. With these ranges, a mathematical model was made using fourth-order polynomial regressions with a correlation of 0.9993, ensuring a safety factor of four in which von Misses forces of the microneedle are around 17.931 MPa; the ANSYS software was used to analyze the mechanical behavior of the microneedles. In addition, the microneedle concept was made by 3D printing using a bio-compatible resin of class 1. The features presented by the microneedle designed in this study make it a promising option for implementation in a transdermal drug-delivery device.

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