Microneedle arrays (MNA) are considered as one of the most promising resources to achieve systemic effects by transdermal delivery of drugs. They are designed as a minimally invasive, painless system which can bypass the stratumcorneum, overcoming the potential drawbacks of subcutaneous injections and other transdermal delivery systems such as chemical enhancers, nano and microparticles, or physical treatments. As a trendy field in pharmaceutical and biomedical research, its applications are constantly evolving, even though they are based on very well-established techniques. The number of molecules administered by MNA are also increasing, with insulin and vaccines administration being the most investigated. Furthermore, MNA are being used to deliver cells and applied in other organs and tissues like the eyes and buccal mucosae. This review intends to offer a general overview of the current state of MNA research, focusing on the strategies, applications, and types of molecules delivered recently by these systems. In addition, some information about the materials and manufacturing processes is presented and safety data is discussed.
3D printing has been widely used for the personalization of therapies and on-demand production of complex pharmaceutical forms. Recently, 3D printing has been explored as a tool for the development of topical dosage forms and wound dressings. Thus, this review aims to present advances related to the use of 3D printing for the development of pharmaceutical and biomedical products for topical skin applications, covering plain dressing and products for the delivery of active ingredients to the skin. Based on the data acquired, the important growth in the number of publications over the last years confirms its interest. The semisolid extrusion technique has been the most reported one, probably because it allows the use of a broad range of polymers, creating the most diverse therapeutic approaches. 3D printing has been an excellent field for customizing dressings, according to individual needs. Studies discussed here imply the use of metals, nanoparticles, drugs, natural compounds and proteins and peptides for the treatment of wound healing, acne, pain relief, and anti-wrinkle, among others. The confluence of 3D printing and topical applications has undeniable advantages, and we would like to encourage the research groups to explore this field to improve the patient’s life quality, adherence and treatment efficacy.
11 April 2023 in WIREs Nanomedicine and Nanobiotechnology
Transdermal delivery of drugs offers an interesting alternative for the administration of molecules that present certain troubles when delivered by the oral route. It can produce systemic effects or perform a local action when the formulation exerts an optimal controlled drug release or a targeted delivery to the specific cell type or site. It also avoids several inconveniences of the oral administration such as the hepatic first pass effect, gastric pH‐induced hydrolysis, drug malabsorption because of certain diseases or surgeries, and unpleasant organoleptic properties. Nanomedicine and microneedle array patches (MAPs) are two of the trendiest delivery systems applied to transdermal research nowadays. However, the skin is a protective barrier and nanoparticles (NPs) cannot pass through the intact stratum corneum. The association of NPs and MAPs (NPs@MAPs) work synergistically, since MAPs assist NPs to bypass the outer skin layers, and NPs contribute to the system providing controlled drug release and targeted delivery. Vaccination and tailored therapies have been proposed as fields where both NPs and MAPs have great potential due to inherent characteristics. MAPs conception and easy use could allow self‐administration and therefore facilitate mass vaccination campaigns in undeveloped areas with weak healthcare services. Additionally, nanomedicine is being explored as a platform to personalize therapies in such an important field as oncology. In this work we show recent insights that prove the benefits of NPs@MAPs association and analyze the prospects and the discrete interest of the industry in NPs@MAPs, evaluating different limiting steps that restricts NPs@MAPs translation to the clinical practice.This article is categorized under: Nanotechnology Approaches to Biology > NA Therapeutic Approaches and Drug Discovery > NA
Atopic dermatitis (AD) and psoriasis are the most common chronic inflammatory skin disorders, which importantly affect the quality of life of patients who suffer them. Among other causes, nitric oxide has been reported as part of the triggering factors in the pathogenesis of both conditions. Cyanocobalamin (vitamin B12) has shown efficacy as a nitric oxide scavenger and some clinical trials have given positive outcomes in its use for treating skin pathologies. Passive skin diffusion is possible only for drugs with low molecular weights and intermediate lipophilicity. Unfortunately, the molecular weight and hydrophilicity of vitamin B12 do not predict its effective diffusion through the skin. The aim of this work was to design new lipid vesicles to encapsulate the vitamin B12 to enhance its skin penetration. Nine prototypes of vesicles were generated and characterized in terms of size, polydispersity, surface charge, drug encapsulation, flexibility, and stability with positive results. Additionally, their ability to release the drug content in a controlled manner was demonstrated. Finally, we found that these lipid vesicle formulations facilitated the penetration of cyanocobalamin to the deeper layers of the skin. The present work shows a promising system to effectively administer vitamin B12 topically, which could be of interest in the treatment of skin diseases such as AD and psoriasis.
An increased interest in colonic drug delivery has led to a higher focus on the design of delivery devices targeting this part of the gastrointestinal tract. Microcontainers have previously facilitated an increase in oral bioavailability of drugs. The surface texture and shape of microcontainers have proven to influence the mucoadhesion ex vivo. In the present work, these findings were further investigated using an in situ closed-loop perfusion technique in the rat colon, which allowed for simultaneous evaluation of mucoadhesion of the microcontainers as well as drug absorption. Cylindrical, triangular and cubic microcontainers, with the same exterior surface area, were evaluated based on in vitro release, in situ mucoadhesion and in situ absorption of amoxicillin. Additionally, the mucoadhesion of empty cylindrical microcontainers with and without pillars on the top surface was investigated. From the microscopy analysis of the colon sections after the in situ study, it was evident that a significantly higher percentage of cubic microcontainers than cylindrical microcontainers adhered to the intestinal mucus. Furthermore, the absorption rate constants and blood samples indicated that amoxicillin in cubic microcontainers was absorbed more readily than when cylindrical or triangular microcontainers were dosed. This could be due to a higher degree of mucoadhesion for these particular microcontainers.
21 September 2024 in Journal of Controlled Release
Inflammatory diseases of the skin have a considerable high prevalence worldwide and negatively impact the patients' quality of life. First-line standard therapies for these conditions inherently entail important side effects when used long-term, particularly complicating the management of chronic cases. Therefore, there is a need to develop novel therapeutic strategies to offer reliable alternative treatments. Abnormally high reactive oxygen species (ROS) levels are characteristic of this kind of illnesses, and therefore a reasonable therapeutic goal. Cyanocobalamin, also known as Vitamin B12, possesses notable antioxidant and ROS-scavenging properties which could make it a possible therapeutic alternative. However, its considerable molecular weight restricts passive diffusion through the skin and forces the use of an advanced transdermal delivery system. Here, we present several prototypes of Cyanocobalamin-loaded Dissolving Microarray Patches (B12@DMAPs) with adequate mechanical properties to effectively penetrate the stratum corneum barrier, allowing drug deposition into the skin structure. Ex vivo penetration and permeability studies noted an effective drug presence within the dermal skin layers; in vitro compatibility studies in representative cell skin cell lines such as L929 fibroblasts and HaCaT keratinocytes ensured their safe use. The in vivo efficacy of the selected prototype was tested in a delayed-type hypersensitivity murine model that mimics an inflammatory skin process. Several findings such as a reduction of MPO-related photon emission in a bioluminescence study, protection against histological damage, and decrease of inflammatory cytokines levels point out the effectivity of B12@DMAPs to downregulate the skin inflammatory environment. Overall, B12@DMAPs offer a cost-effective translational alternative for improving patients' skin healthcare.