Nanotechnology-based alternatives for the topical delivery of immunosuppressive agents in psoriasis.

Psoriasis is a recurring, immune-mediated dermatological disorder. Many therapeutic agents are available for the treatment of psoriasis, including immunosuppressants and biologic treatments with immunosuppressant action. The employment of nanotechnology allows drug tailoring to achieve dermal targeting, improve efficacy and minimize undesirable effects. Here we discuss the use of the topical route in combination with nano-based drug delivery systems containing immunosuppressants for the management of psoriasis. This review is based on articles selected from 2011 to 2022, using the keywords "Psoriasis" AND "Immunosuppressants" AND "Nano*" in the main databases. Fifty-seven articles were retrieved, although only forty-two matched the inclusion criteria. Nanocarriers such as liposomes, ethosomes, niosomes, solid lipid nanoparticle, nanostructured lipid carriers and microspheres containing immunosuppressive drugs (methotrexate, cyclosporine, tacrolimus, and etanercept) were identified. The main findings of these studies are related to the improved in vitro/ex vivo permeation/penetration and therapeutic efficacy of nanoparticles in vitro and in vivo, compared to the drug in solution. Based on the studies discussed in this review, encapsulation in several types of nanocarriers decreases toxicity, dose, and dose frequency. Furthermore, it enables specific targeting of the active drug, pointing to the possibility of improving topical therapy for psoriasis. In conclusion, nanoformulations represent a novel and promising tool for psoriasis treatment.

Data of characterization and related assays of lipid-core nanocapsule formulations and their hydrolysis mechanism.

The data presented here are related to the research paper entitled "Chemical stability, mass loss and hydrolysis mechanism of sterile and non-sterile lipid-core nanocapsules: the influence of the molar mass of the polymer wall," [1]. Experimental details of the nanoemulsion and nanosphere preparation. Sterilization methodology and their efficacy by microbiological analyses (turbidimetry and fungi and bacteria detection). Characterization data of formulations, LNC 1, LNC 2 and LNC 3, analyzed by laser diffraction and DLS analysis, as well as, characterization data of degradation by SEC, including all statistics analyses.

An Inhalable Powder Formulation Based on Micro- and Nanoparticles Containing 5-Fluorouracil for the Treatment of Metastatic Melanoma.

Melanoma is the most aggressive and lethal type of skin cancer, with a poor prognosis because of the potential for metastatic spread. The aim was to develop innovative powder formulations for the treatment of metastatic melanoma based on micro- and nanocarriers containing 5-fluorouracil (5FU) for pulmonary administration, aiming at local and systemic action. Therefore, two innovative inhalable powder formulations were produced by spray-drying using chondroitin sulfate as a structuring polymer: (a) 5FU nanoparticles obtained by piezoelectric atomization (5FU-NS) and (b) 5FU microparticles of the mucoadhesive agent Methocel™ F4M for sustained release produced by conventional spray drying (5FU-MS). The physicochemical and aerodynamic were evaluated in vitro for both systems, proving to be attractive for pulmonary delivery. The theoretical aerodynamic diameters obtained were 0.322 ± 0.07 µm (5FU-NS) and 1.138 ± 0.54 µm (5FU-MS). The fraction of respirable particles (FR%) were 76.84 ± 0.07% (5FU-NS) and 55.01 ± 2.91% (5FU-MS). The in vitro mucoadhesive properties exhibited significant adhesion efficiency in the presence of Methocel™ F4M. 5FU-MS and 5FU-NS were tested for their cytotoxic action on melanoma cancer cells (A2058 and A375) and both showed a cytotoxic effect similar to 5FU pure at concentrations of 4.3 and 1.7-fold lower, respectively.

The use of chitosan as cationic coating or gel vehicle for polymeric nanocapsules: Increasing penetration and adhesion of imiquimod in vaginal tissue.

The human papillomavirus (HPV) infection, which is strongly related to cervical cancer, can be reduced by the topical application of imiquimod. Some strategies have been used to increase the adhesion and penetration of drugs through the vaginal mucosa. Two of them are the development of mucoadhesive semisolid formulations and the development of polymeric nanocarriers. In this paper, we hypothesize that the combined use of these two strategies results in a better performance of the formulation to retain imiquimod into the vaginal tissue. Aiming this, two different systems are proposed: (a) chitosan-coated poly(ε-caprolactone)-nanocapsules incorporated into hydroxyethylcellulose gel (HEC-NCimiq-chit), and (b) poly(ε-caprolactone)-nanocapsules incorporated into chitosan hydrogel (CHIT-NCimiq). These formulations were submitted to three main tests: mucoadhesivity by interaction, permeation and washability test (or retention test). We developed an integrative index that allows comparing the global performance of the proposed formulations by considering jointly the results of these three tests. Thus, when considered the integrative indexes for the formulations, our results show that CHIT-NCimiq presents the best performance for the treatment of HPV.

Nanoencapsulation of Rose-Hip Oil Prevents Oil Oxidation and Allows Obtainment of Gel and Film Topical Formulations.

The rose-hip oil holds skin regenerating properties with applications in the dermatological and cosmetic area. Its nanoencapsulation might favor the oil stability and its incorporation into hydrophilic formulations, besides increasing the contact with the skin and prolonging its effect. The aim of the present investigation was to develop suitable rose-hip-oil-loaded nanocapsules, to verify the nanocapsule effect on the UV-induced oxidation of the oil and to obtain topical formulations by the incorporation of the nanocapsules into chitosan gel and film. The rose-hip oil (500 or 600 µL), polymer (Eudragit RS100®, 100 or 200 mg), and acetone (50 or 100 mL) contents were separately varied aiming to obtain an adequate size distribution. The results led to a combination of the factors acetone and oil. The developed formulation showed average diameter of 158 ± 6 nm with low polydispersity, pH of 5.8 ± 0.9, zeta potential of +9.8 ± 1.5 mV, rose-hip oil content of 54 ± 1 µL/mL and tendency to reversible creaming. No differences were observed in the nanocapsules properties after storage. The nanoencapsulation of rose-hip oil decreased the UVA and UVC oxidation of the oil. The chitosan gel and film containing rose-hip-oil-loaded nanocapsules showed suitable properties for cutaneous use. In conclusion, it was possible to successfully obtain rose-hip-oil-loaded nanocapsules and to confirm the nanocapsules effect in protecting the oil from the UV rays. The chitosan gel and film were considered interesting alternatives for incorporating the nanoencapsulated rose-hip oil, combining the advantages of the nanoparticles to the advantages of chitosan.

Co-encapsulation of imiquimod and copaiba oil in novel nanostructured systems: promising formulations against skin carcinoma.

In this study, two types of cutaneous-directed nanoparticles are proposed for the co-encapsulation of imiquimod (a drug approved for the treatment of basal cell carcinoma) and copaiba oil (oil that exhibits anti-proliferative properties). Nanostructured copaiba capsules (NCCImq) were prepared using the interfacial deposition method, and nanostructured Brazilian lipids (NBLImq) were prepared by high-pressure homogenization. The formulations exhibited average diameter, zeta potential, pH and drug content of approximately 200nm, -12mV, 6 and 1mgmL(-1), respectively. In addition, the formulations exhibited homogeneity regarding particle size, high encapsulation efficiency and stability. Both nanocarriers controlled imiquimod release, and NBLImq exhibited slower drug release (p < 0.05), likely due to increased interaction of the drug with the solid lipid (cupuaçu seed butter). The in vitro evaluation of the imiquimod-loaded nanocarriers was performed using healthy skin cells (keratinocytes, HaCaT); no alteration was observed, suggesting the biocompatibility of the nanocarriers. In addition, in vitro skin permeation/penetration using pig skin was performed, and NCCImq led to increased drug retention in the skin layers and reduced amounts of drug found in the receiver solution. Thus, NCCImq is considered the most promising nanoformulation for the treatment of skin carcinoma.

Improving drug biological effects by encapsulation into polymeric nanocapsules.

This review is based on selected reports from 2004 to 2014 and provides a comprehensive and updated overview of the state of the art related to the drug delivery advantages of polymeric nanocapsules, which are a specific type of polymeric nanoparticles used for improvement of biological effects. Special attention is given to the application of nanocapsules to increase the chemical and photostability of drugs, to modulate the interaction with cells and tissues, to reduce adverse effects of drugs, and to increase the drug efficiency and/or bioavailability. Moreover, this review covers in vitro and in vivo studies, highlighting interesting examples of drugs from several therapeutic classes for which efficacy is improved by encapsulation in different types of nanocapsules, especially in lipid-core nanocapsules. We also briefly present the first results obtained so far attesting to the safety of using polymeric nanocapsules for drug delivery.

Chitosan gel containing polymeric nanocapsules: a new formulation for vaginal drug delivery.

The vaginal route of administration is an alternative for several treatments for either local or systemic pharmacological effects. However, the permanence of a drug in this route represents a challenge for formulation development that can be overcome by using nanoencapsulation and chitosan gel. Thus, this work aimed to evaluate the performance of chitosan hydrogels containing cationic and anionic acrylic-based nanocapsules (Eudragit RS 100 and Eudragit S 100, respectively) with Nile red as a model of lipophilic substance in the vaginal route of administration, as measured by increases in the residence time and the penetration of these formulations. Several formulations were prepared with increasing chitosan concentrations, and were analyzed in terms of pH and rheological behavior so that the most suitable formulation could be selected. The enhancement of the adhesion (tensile stress test and washability profile) and penetration (confocal laser scanning microscopy and extraction followed by quantification) properties of the formulations, when applied to porcine vaginal mucosa, were evaluated. The nanocapsule suspensions produced presented adequate properties: size of approximately 200 nm (polydispersity index of ≤0.2); zeta potential around +10 mV for the cationic formulation and -10 mV for the anionic formulation; and pH values of 6.1±0.1 (Eudragit RS 100), 5.3±0.2 (Eudragit S 100), 6.2±0.1 (Nile red loaded Eudragit RS 100), and 5.1±0.1 (Nile red loaded Eudragit S 100). The chitosan formulation presented suitable viscosity for vaginal application and acidic pH (approximately 4.5). The tensile stress test showed that both formulations containing polymeric nanocapsules presented higher mucoadhesion when compared with the formulation without nanocapsules. In the washability experiment, no significant differences were found between formulations. Confocal microscopy and fluorescence quantification after extraction from the mucosa showed higher penetration of Nile red when it was nanoencapsulated, particularly in cationic nanocapsules. The formulations developed based on chitosan gel vehicle at 2.5% weight/weight containing polymeric nanocapsules, especially the cationic nanocapsules, demonstrated applicability for the vaginal delivery of hydrophobic substances.

The use of nanoencapsulation to decrease human skin irritation caused by capsaicinoids.

Capsaicin, a topical analgesic used in the treatment of chronic pain, has irritant properties that frequently interrupt its use. In this work, the effect of nanoencapsulation of the main capsaicinoids (capsaicin and dihydrocapsaicin) on skin irritation was tested in humans. Skin tolerance of a novel vehicle composed of chitosan hydrogel containing nonloaded nanocapsules (CH-NC) was also evaluated. The chitosan hydrogel containing nanoencapsulated capsaicinoids (CH-NC-CP) did not cause skin irritation, as measured by an erythema probe and on a visual scale, while a formulation containing free capsaicinoids (chitosan gel with hydroalcoholic solution [CH-ET-CP]) and a commercially available capsaicinoids formulation caused skin irritation. Thirty-one percent of volunteers reported slight irritation one hour after application of CH-NC-CP, while moderate (46% [CH-ET-CP] and 23% [commercial product]) and severe (8% [CH-ET-CP] and 69% [commercial product]) irritation were described for the formulations containing free capsaicinoids. When CH-NC was applied to the skin, erythema was not observed and only 8% of volunteers felt slight irritation, which demonstrates the utility of the novel vehicle. A complementary in vitro skin permeation study showed that permeation of capsaicinoids through an epidermal human membrane was reduced but not prevented by nanoencapsulation.