Introduction: Dermal and transdermal drug delivery systems offer the possibility to control the release of the drug for an extended period of time. In particular, skin-delivery of local anesthetics (LA) is one of the most important strategies to increase the local drug concentration and to reduce systemic adverse reactions. Areas covered: During the development phase of new formulations for skin-delivery of LA one should consider a set of desirable features such providing suitable adhesion, easy application/removal and also to be biocompatible, biodegradable and non-toxic. This review emphasizes the main strategies for skin-delivery of LA considering those features in relation to the composition of the delivery systems described. The topics highlight the relationships between physico-chemical studies and pharmaceutical applications for liposomes and solid lipid nanoparticles as well as the formulation and clinical applications for hydrogels and patches. Expert opinion: The development of LA skin-delivery systems using hydrogels and different permeation enhancers, liposomes or lipid nanoparticles (as isolated carrier systems or as their dispersion in a gel-base) and patches have been explored as alternatives to commercial formulations, modifying the release rate of LA, increasing bioadhesive properties and reducing toxicity, resulting in an improved therapeutic efficacy. This review should provide to the reader a special emphasis on four delivery-systems, comprising the group of liposomes and lipid nanoparticles, hydrogels and patches technologies looking forward their application for skin anesthesia.

The Aloe vera (L.) Burman f. pulp extract (AE), obtained from the inner parts of Aloe vera leaves, is rich in polysaccharides, including glucomannans, acemannans, pectic compounds, cellulose, and hemicelluloses; acemannan and glucomannan are considered the two main components responsible for most of the plant’s therapeutical properties. Besides having anti-inflammatory activity, these polysaccharides accelerate wound healing and promote skin regeneration, thus they can be utilized in healing products. The objective of this study was to develop Aloe vera mucilaginous-based hydrogels for topical use in psoriasis treatment. The hydrogels were prepared with 80% w/w of A. vera mucilaginous gel, evaluating two distinct polymers as the gelling agent: 1% carbopol 940 (FC1 and FC2) or 2% hydroxyethylcellulose (FH3 and FH4). FC1, FC2, FH3 and FH4 were evaluated for their organoleptic characteristics, rheological properties, pH and glucomannan content. Polysaccharide fractions (PFs) were extracted from the AE and used as a group of chemical markers and characterized by infrared (IR) spectroscopy and 1H nuclear magnetic resonance (₁H NMR). The quantification of these markers in the raw material (AE) and in the hydrogels was carried out using spectrophotometric techniques in the UV-VIS region. The hydrogels-based hydroxyethylcellulose (FH3 and FH4) had glucomannan contents of 6.76 and 4.01 mg/g, respectively. Formulations with carbopol, FC1 and FC2, had glucomannan contents of 8.69 and 9.17 mg/g, respectively, an ideal pH for application on psoriasis, in addition to good spreadability and pseudoplastic and thixotropic behavior. Considering these results, hydrogel FC1 was evaluated for its keratolytic activity in a murine model of hyperkeratinization. For that, 0.5 mL of test formulations FC1 and FPC (0.05% clobetasol propionate cream) were topically applied to the proximal region of adult rats daily for 13 days. After euthanasia, approximately 2.5 cm of the proximal portion of each animal’s tail was cut and placed in 10% buffered formalin. Then, each tail fragment was processed and stained with hematoxylin and eosin (HE), and the results obtained from the histological sections indicated a 61% reduction in stratum corneum for animals treated with the A. vera hydrogel (FC1G) and 66% for animals treated with clobetasol propionate (PCG), compared to the group of animals that did not receive treatment (WTG). This study led to the conclusion that compared to the classic treatment (clobetasol propionate), the 80% A. vera hydrogel showed no significant difference, being effective in controlling hyperkeratinization.

Dibucaine (DBC) is among the more potent long-acting local anesthetics (LA), and it is also one of the most toxic. Over the last decades, solid lipid nanoparticles (SLN) have been developed as promising carriers for drug delivery. In this study, SLN formulations were prepared with the aim of prolonging DBC release and reducing its toxicity. To this end, SLN composed of two different lipid matrices and prepared by two different hot-emulsion techniques (high-pressure procedure and sonication) were compared. The colloidal stability of the SLN formulations was tracked in terms of particle size (nm), polydispersity index (PDI), and zeta potential (mV) for 240 days at 4 °C; the DBC encapsulation efficiency was determined by the ultrafiltration/centrifugation method. The formulations were characterized by differential scanning calorimetry (DSC), electron paramagnetic resonance (EPR), and release kinetic experiments. Finally, the in vitro cytotoxicity against 3T3 fibroblast and HaCaT cells was determined, and the in vivo analgesic action was assessed using the tail flick test in rats. Both of the homogenization procedures were found suitable to produce particles in the 200 nm range, with good shelf stability (240 days) and high DBC encapsulation efficiency (~72–89%). DSC results disclosed structural information on the nanoparticles, such as the lower crystallinity of the lipid core vs. the bulk lipid. EPR measurements provided evidence of DBC partitioning in both SLNs. In vitro (cytotoxicity) and in vivo (tail flick) experiments revealed that the encapsulation of DBC into nanoparticles reduces its intrinsic cytotoxicity and prolongs the anesthetic effect, respectively. These results show that the SLNs produced are safe and have great potential to extend the applications of dibucaine by enhancing its bioavailability.

Hydrogels are a great ally in the pharmaceutical and biomedical areas. They have a three-dimensional polymeric structure that allows the swelling of aqueous fluids, acting as an absorbent, or encapsulating bioactive agents for controlled drug release. Interestingly, plants are a source of biogels, specifically polysaccharides, composed of sugar monomers. The crosslinking of these polymeric chains forms an architecture similar to the extracellular matrix, enhancing the biocompatibility of such materials. Moreover, the rich hydroxyl monomers promote a hydrophilic behavior for these plant-derived polysaccharide gels, enabling their biodegradability and antimicrobial effects. From an economic point of view, such biogels help the circular economy, as a green material can be obtained with a low cost of production. As regards the bio aspect, it is astonishingly attractive since the raw materials (polysaccharides from plants-cellulose, hemicelluloses, lignin, inulin, pectin, starch, guar, and cashew gums, etc.) might be produced sustainably. Such properties make viable the applications of these biogels in contact with the human body, especially incorporating drugs for controlled release. In this context, this review describes some sources of plant-derived polysaccharide gels, their biological function, main methods for extraction, remarkable applications, and properties in the health field.

Background: One of the major clinical challenges is to achieve a rapid and efficient treatment of complex chronic wounds. Nowadays, most wound dressings currently available are unable to find a solution the challenges of resistance to bacterial infection, protein adsorption and increased levels of exudates. Natural inorganic ingredients (clay minerals, metal cations, zeolites, etc) could be the key to solve the problem satisfactorily. Some of these materials have shown biocompatibility and ability to enhance cell adhesion, proliferation and cellular differentiation and uptake. Besides, some natural inorganic ingredients effectively retain drugs, allowing the design of drug delivery matrices. Objective: possibilities of natural inorganic ingredients in wound healing treatments have been reviewed, the following sections have been included: 1. Introduction 2. Functions of Inorganic Ingredients in wound healing 2.1. Antimicrobial effects 2.2. Hemostatic effects 3. Clay minerals for wound healing 3.1. Clay minerals 3.2. Clay mineral semisolid formulations 3.3. Clay/polymer composites and nanocomposites 3.4. Clay minerals in wound dressings 4. Other inorganic materials for wound healing 4.1. Zeolites 4.2. Silica and other silicates 4.3. Other minerals 4.4. Transition metals 5. Conclusion Conclusion: inorganic ingredients possess useful features in the development of chronic wounds advanced treatments. They improve physical (mechanical resistance and water vapor transmission), chemical (release of drugs, hemostasis and/or adsorption of exudates and moisture) and biological (antimicrobial effects and improvement of healing) properties of wound dressings. In summary, inorganic ingredients have proved to be a promising and easily accessible products in the treatment of wounds and, more importantly, chronic wounds.