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1.
Nanoscale ; 13(30): 12916-12928, 2021 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-34477775

RESUMO

One of the most realistic approaches for delivering actives (pharmaceuticals/cosmetics) deep into skin layers is encapsulation into nanoparticles (NPs). Nonetheless, molecular-level mechanisms related to active delivery from NPs to the skin have scarcely been studied despite the large number of synthesis and characterization studies. We herein report the underlying mechanism of active translocation and permeation through the outermost layer of skin, the stratum corneum (SC), via molecular dynamics (MD) simulations complemented by experimental studies. A SC molecular model is constructed using current state-of-the-art methodology via incorporating the three most abundant skin lipids: ceramides, free fatty acids, and cholesterol. As a potent antioxidant, ferulic acid (FA) is used as the model active, and it is loaded into Gelucire 50/13 NP. MD simulations elucidate that, first, FA-loaded NP approaches the skin surface quickly, followed by slight penetration and adsorption onto the upper skin surface; FA then translocates from the NP surface to the skin surface due to stronger NP-skin interactions compared to the FA-NP interactions; then, once FA is released onto the skin surface, it slowly permeates deep into the skin bilayer. Both the free energy and resistance to permeation not only indicate the spontaneous transfer of FA from the bulk to the skin surface, but they also reveal that the main barrier against permeation exists in the middle of the lipid hydrophobic tails. Significantly lower diffusion of FA is obtained in the main barrier region compared to the bulk. The estimated permeability coefficient (log P) values are found to be higher than the experimental values. Importantly, the permeation process evaluated via MD simulations perfectly matches with experiments. The study suggests a molecular simulation platform that provides various crucial insights relating to active delivery from loaded NP to skin, and it could facilitate the design and development of novel NP-based formulations for transdermal delivery and the topical application of drugs/cosmetics.


Assuntos
Simulação de Dinâmica Molecular , Nanopartículas , Administração Cutânea , Bicamadas Lipídicas , Lipídeos , Permeabilidade , Pele
2.
Eur J Med Res ; 26(1): 95, 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34412706

RESUMO

BACKGROUND: Red scrotum syndrome is typically described as well-demarcated erythema of the anterior scrotum accompanied by persistent itching and burning. It is chronic and difficult to treat and contributes to significant psychological distress and reduction in quality of life. The medical literature surrounding the condition is sparse, with the prevalence likely under-recognized and the pathophysiology remaining poorly understood. Formation of a cutaneous microbial biofilm has not been proposed as an underlying etiology. Microbial biofilms can form whenever microorganisms are suspended in fluid on a surface for a prolonged time and are becoming increasingly recognized as important contributors to medical disease (e.g., chronic wounds). CASE PRESENTATION: A 26-year-old man abruptly developed well-demarcated erythema of the bilateral scrotum after vaginal secretions were left covering the scrotum overnight. For 14 months, the patient experienced daily scrotal itching and burning while seeking care from multiple physicians and attempting numerous failed therapies. He eventually obtained complete symptomatic relief with the twice daily application of 0.8% menthol powder. Findings in support of a cutaneous microbial biofilm as the underlying etiology include: (1) the condition began following a typical scenario that would facilitate biofilm formation; (2) the demarcation of erythema precisely follows the scrotal hairline, suggesting that hair follicles acted as scaffolding during biofilm formation; (3) despite resolution of symptoms, the scrotal erythema has persisted, unchanged in boundary 15 years after the condition began; and (4) the erythematous skin demonstrates prolonged retention of gentian violet dye in comparison with adjacent unaffected skin, suggesting the presence of dye-avid material on the skin surface. CONCLUSION: The probability that microorganisms, under proper conditions, can form biofilm on intact skin is poorly recognized. This case presents a compelling argument for a cutaneous microbial biofilm as the underlying cause of red scrotum syndrome in one patient, and a review of similarities with other reported cases suggests the same etiology is likely responsible for a significant portion of the total disease burden. This etiology may also be a significant contributor to the disease burden of vulvodynia, a condition with many similarities to red scrotum syndrome.


Assuntos
Biofilmes , Eritema/patologia , Escroto/patologia , Administração Cutânea , Adulto , Antipruriginosos/administração & dosagem , Antipruriginosos/uso terapêutico , Eritema/tratamento farmacológico , Eritema/microbiologia , Folículo Piloso/microbiologia , Humanos , Masculino , Mentol/administração & dosagem , Mentol/uso terapêutico , Escroto/microbiologia
3.
Int J Clin Pharmacol Ther ; 59(9): 603-609, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34236302

RESUMO

OBJECTIVE: Lidocaine 5% patches are approved for the treatment of post-herpetic neuralgia in adults. Little information is available on the penetration of lidocaine into skin and skin-related soft tissue, which are thought to be closer to the site where lidocaine exerts its pharmacological action on neuronal structures. This pilot study investigated subcutaneous and systemic pharmacokinetics of lidocaine during topical application of two different lidocaine 5% patches. MATERIALS AND METHODS: This randomized two-way, two-period crossover study assessed lidocaine concentrations in subcutaneous tissue (by microdialysis) and plasma of n = 5 healthy subjects during 12-hour-long applications of a recently developed lidocaine 5% patch (Laboratorios Gebro Pharma, SA, Barcelona, Spain) and a marketed reference patch (Versatis 5% lidocaine patch, Grünenthal, Brunn am Gebirge, Austria), respectively. RESULTS: Lidocaine was detectable in subcutaneous tissue within 60 minutes from start of patch application, and in plasma only after a marked delay. The test formulation led to increased exposure to lidocaine in both subcutaneous tissue and plasma. CONCLUSION: This study has underscored the potential of microdialysis to comparatively assess the pharmacokinetics of two different drug formulations and encourages its further use in this area.


Assuntos
Anestésicos Locais , Lidocaína , Administração Cutânea , Adulto , Anestésicos Locais/uso terapêutico , Estudos Cross-Over , Humanos , Microdiálise , Projetos Piloto
4.
Int J Pharm ; 606: 120868, 2021 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-34242628

RESUMO

Hyperpigmentation is a common skin condition with serious psychosocial consequences. Decapeptide-12, a novel peptide, has been found to be safer than hydroquinone in reducing melanin content, with efficacy up to more than 50% upon 16 weeks of twice-daily treatment. However, the peptide suffers from limited transcutaneous penetration due to its hydrophilicity and high molecular weight. Therefore, decapeptide-12 was modified by adding a palmitate chain in an attempt to overcome this limitation. Molecular docking results showed that the two peptides exhibited similar biological activity towards tyrosinase. We also tested the effect of chemical penetration enhancers and microneedles to deliver the two peptides into and through skin, using an in vitro human skin permeation method. It was shown that the palm-peptide achieved the best skin retention owing to the increased lipophilicity. In addition, skin permeation of the palm-peptides was enhanced by the chemical skin penetration enhancers, namely, oleic acid and menthol. Skin permeation of the native peptide was enhanced by the microneedle patch but not the chemical skin penetration enhancers. Cutaneous absorption of the palm-peptides was estimated to have achieved its therapeutic concentration within skin. The combinatory approach of using molecular modification, chemical penetration enhancement, and microneedle patch proves to be useful to enhanceskin permeation of the peptides.


Assuntos
Absorção Cutânea , Pele , Administração Cutânea , Humanos , Simulação de Acoplamento Molecular , Peptídeos/metabolismo , Pele/metabolismo
5.
Int J Pharm ; 606: 120885, 2021 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-34271153

RESUMO

Finasteride (FND) is a competitive inhibitor of 5α-reductase, an enzyme involved in benign prostatic hyperplasia (BPH) and androgenic alopecia. FND is administered in oral, often lifelong treatments, increasing the pill burden of polymedicated patients. Microneedle array patches (MAPs) are minimally invasive devices that painlessly pierce the outermost layers of the skin, forming slowly-dissolving drug depots in the dermis, which can release drugs over weeks or months, making this platform an attractive, patient-friendly option for long-term treatments. This work describes the development of long-acting dissolving and implantable PLGA MAPs aimed for systemic release of FND for at least two weeks. Mechanically strong tip-loaded MAPs with pyramidal geometry were obtained using micromoulding methodology. In vitro studies revealed that the dissolving and implantable MAPs were able to release the drug for over 7 and 14 days, respectively. Skin deposition experiments in Franz cells demonstrated that after 24 h, dissolving and implantable MAPs were able to deposit 629.00 ± 214.54 µg and 1861.64 ± 383.30 µg of FND in the skin, respectively. On the other hand, transdermal permeation studies showed that both formulations produced a slow release of the drug to the receptor compartment of the Franz cells, with dissolving and implantable MAPs releasing 90.43 ± 6.20 µg and 27.80 ± 3.94 µg of FND after 24 h. The formulations described here could be an alternative to current oral treatments, having the potential to deliver the drug for extended periods, simplifying the treatment of BPH and androgenic alopecia.


Assuntos
Finasterida , Agulhas , Administração Cutânea , Preparações de Ação Retardada , Sistemas de Liberação de Medicamentos , Humanos , Pele
6.
Colloids Surf B Biointerfaces ; 206: 111978, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34293580

RESUMO

We have developed a microemulsion (ME)-based hydrogel, containing propylene glycol, Azone®, Labrasol®, isobutanol and water (20:3:18:3:56), for the transdermal delivery of rivaroxaban (RVX). Formulation ME-1:RVX, which was loaded with 0.3 mg/g of RVX, presented as a clear, homogenous fluid with a droplet size of 82.01 ± 6.32 nm and a PdI of 0.207 ± 0.01. To provide gelation properties, 20 % (w/w) of Pluronic® F-127 was added to ME-1:RVX to generate formulation PME-1a. An added benefit was an increased capacity for RVX to 0.4 mg/g (formulation PME-1b). PME-1b displayed spherical droplets with a nanoscale diameter as observed by Transmission Electron Microscopy. The release of RVX from PME-1b was 20.71 ± 0.76 µg/cm2 with a permeation through pig epidermis of 18.32 ± 8.87 µg/cm2 as measured in a Franz Cell for 24 h. PME-1b presented a pseudoplastic behavior, pH value compatible with the skin and good stability over 60 days at room and elevated temperatures. The prothrombin time was assessed for each concentration of RVX obtained in the permeation assay and each demonstrated a relevant anticoagulant activity. PME-1b also presented no cytotoxicity against HaCaT cells. Utilizing GastroPlus® software, an in silico analysis was performed to simulate the delivery of PME-1b through a transdermal system that suggested a minimum dose of RVX for the treatment and prevention of venous thromboembolism could be achieved with an 8 h administration regimen. These results suggest that PME-1b is a promising transdermal formulation for the effective delivery of RVX that could be a viable alternative for the treatment and prevention of venous thromboembolism.


Assuntos
Rivaroxabana , Tromboembolia Venosa , Administração Cutânea , Animais , Emulsões , Hidrogéis , Pele , Suínos
7.
Int J Pharm ; 606: 120882, 2021 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-34298102

RESUMO

With the need for safe and efficacious vaccines which could be administered via non-invasive procedure, alternatives to traditional injectables vaccines are sought after. The present study aimed to develop the microparticulate formulation of measles vaccine and explore the feasibility of transdermal delivery via ablative laser mediated skin microporation. Transdermal route offers several advantages including painless immunization and ease of administration. We propose to use P.L.E.A.S.E. ablative laser for transdermal immunization of the microparticulate measles vaccine. This laser emits energy at 2940 µm, enabling cold ablation. This creates the micropores of defined size for delivery of vaccines into the skin. We compared the efficacy of transdermal immunization using the particulate formulation of the vaccine to that of traditional subcutaneous immunization using soluble and particulate vaccine. The microparticles were formulated using the biocompatible and biodegradable bovine serum albumin (BSA)-based polymer matrix. These vaccine microparticles were non-cytotoxic to the antigen presenting cells (APCs) and could effectively stimulate the innate immune response, confirmed by release of nitric oxide (NO) from the Griess's assay. The APCs when exposed to vaccine microparticles also showed a significantly higher expression of antigen-presenting molecules, MHC I and MHC II, and their co-stimulatory molecules, CD80 and CD40 as compared to the blank microparticles. The microparticulate measles vaccine was evaluated in vivo in the murine model. We compared the serum IgG and IgM levels in the mice receiving the vaccine subcutaneously and transdermally post-immunization. The results revealed that transdermal immunization with microparticulate vaccine is as efficient as the traditional subcutaneous administration.


Assuntos
Imunização , Vacina contra Sarampo , Administração Cutânea , Animais , Lasers , Camundongos , Vacinação
8.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(4): 543-547, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34323028

RESUMO

The transformersome is a new kind of lipoid drug delivery carrier. It has a number of excellent properties, including deformability, pressure permeability, and amphiphilicity. It has been widely used in the field of percutaneous and oral administration of medication. However, due to factors concerning its formulation, the stability and effectiveness of intravenous injection and other systemic routes of administration of transfersomes should be carefully examined. As an alternative, the formulation can be enhanced or improved in order to better exploit the strengths and avoid the weaknesses. Because of its deformability, transfersome may have distinctive potential strengths in the penetration of physiological barriers, for example, the blood-brain barrier, and in the research and development of transdermal immunization vaccines. This review has summarized five aspects of transfersomes, including the main properties, the formulation and process influencing factors, evaluation methods, main administration routes, and problems. Herein, we have given some examples and analysis, summarized the research achievements and assessd prospects for future development.


Assuntos
Sistemas de Liberação de Medicamentos , Lipossomos , Administração Cutânea , Portadores de Fármacos , Pesquisa , Pele
9.
Hautarzt ; 72(8): 676-685, 2021 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-34223936

RESUMO

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease of the skin folds, which requires more outpatient treatment alternatives. Although the disease was previously treated using surgery, new treatment modalities now allow the effective treatment of mild and moderate cases in an ambulatory care setting. AIM OF STUDY: Local and instrument-based therapies are presented and their efficacy and safety profiles are highlighted. MATERIALS AND METHODS: Clinical evidence for each therapeutic modality are presented and current treatment developments are analyzed based on the future treatment of HS patients in Germany. RESULTS: Effective treatments for outpatient care of HS patients include topical clindamycin, resorcinol, and intralesional corticosteroids. New devices such as LAight therapy (combining intense pulsed light [IPL] with radiofrequency) are available, which can be used as monotherapy or adjunct therapy in combination with systemic treatment and/or surgery for the management of HS. CONCLUSION: Evidence-based use of local treatments can provide more efficient outpatient and self-administered strategies, which improves the quality of life of HS patients, especially for patients with recurrent mild and moderate disease.


Assuntos
Hidradenite Supurativa , Administração Cutânea , Doença Crônica , Alemanha , Hidradenite Supurativa/tratamento farmacológico , Hidradenite Supurativa/terapia , Humanos , Qualidade de Vida
10.
Ther Deliv ; 12(8): 583-596, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34286598

RESUMO

Aim: The work describes enhanced bioavailability of paliperidone palmitate through transdermal delivery using nanostructured lipid carriers (NLC). Materials & methods: NLCs were formulated by nanoprecipitation method followed by incorporation in transdermal patch and physicochemical characterization. Results: NLCs showed high percentage entrapment efficiency of 83.44 ± 0.8%, drug loading of 24.75 ± 1.10% (w/w), particle size of 173.8 ± 3.25 nm, polydispersity index of 0.143 ± 0.05 and zeta potential of -15.9 ± 0.75 mV. In vitro and ex vivo studies indicated zero-order controlled drug release from NLCs and transdermal patch up to 48 h. Pharmacokinetic studies indicated 1.76-fold enhanced bioavailability by transdermal route as compared with oral drug delivery. Conclusion: From the results, it was concluded that drug-loaded NLCs-transdermal patch is promising drug delivery system for poorly bioavailable drugs.


Assuntos
Nanoestruturas , Palmitato de Paliperidona , Administração Cutânea , Disponibilidade Biológica , Portadores de Fármacos , Liberação Controlada de Fármacos , Lipídeos , Tamanho da Partícula
11.
Biomed Pharmacother ; 138: 111537, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34311535

RESUMO

Aging of the skin is a complicated bioprocess that is affected by constant exposure to ultraviolet irradiation. The application of herbal-based anti-aging creams is still the best choice for treatment. In the present study, Citrus sinensis L. fruit peels ethanolic extract (CSPE) was formulated into lipid nanoparticles (LNPs) anti-aging cream. Eight different formulations of CSEP-LNPs were prepared and optimized using 23 full factorial designs. In vivo antiaging effect of the best formula was tested in Swiss albino mice where photo-aging was induced by exposure to UV radiation. HPLC-QToF-MS/MS metabolic profiling of CSPE led to the identification of twenty-nine metabolites. CSPE was standardized to a hesperidin content of 15.53 ± 0.152 mg% using RP-HPLC. It was suggested that the optimized formulation (F7) had (245 nm) particle size, (91.065%) EE, and (91.385%) occlusive effect with a spherical and smooth surface. The visible appearance of UV-induced photoaging in mice was significantly improved after topical application on CSPE-NLC cream for 5 weeks, levels of collagen and SOD were significantly increased in CSPE- NLC group, while levels of PGE2, COX2, JNK, MDA, and elastin was reduced. Finally, The prepared anti-aging CSPE-NLC cream represents a safe, convenient, and promising skincare cosmetic product.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Citrus sinensis , Metaloproteinase 13 da Matriz/metabolismo , Extratos Vegetais/administração & dosagem , Envelhecimento da Pele/efeitos dos fármacos , Creme para a Pele/administração & dosagem , Pele/efeitos dos fármacos , Administração Cutânea , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Citrus sinensis/química , Colágeno/metabolismo , Regulação para Baixo , Composição de Medicamentos , Feminino , Frutas , Lipídeos/química , Metaloproteinase 13 da Matriz/genética , Camundongos , Nanopartículas , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Pele/enzimologia , Pele/patologia , Pele/efeitos da radiação , Creme para a Pele/química , Creme para a Pele/isolamento & purificação , Superóxido Dismutase/metabolismo , Raios Ultravioleta
12.
Mater Sci Eng C Mater Biol Appl ; 127: 112226, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34225871

RESUMO

In this work, we introduce, for the first time, novel hybrid microneedle patches with implantable poly(lactic-co-glycolic acid) (PLGA) tips aligned with hydrogel-forming microneedle bases (HFMB) using a dissolvable material. A model dye, Nile red, and an antifungal drug, amphotericin B, were loaded into the PLGA tips in a controlled manner by multiple castings. Three different types of pre-formed microneedle bases including conventional dissolving baseplates (MN0), HFMB with needle heights of 600 µm (MN6) and HFMB with needle heights of 800 µm (MN8) were investigated. Compared to the conventional dissolving baseplate (MN0)-based PLGA tipped implantable microneedle design, the addition of the pre-formed HFMB (MN8) improved in vitro and ex vivo insertion capacities of the patches, increased ex vivo drug delivery efficiency up to 80% of the loaded drug and speeded up the implantation process to within 1 min. An adhesion test indicated that the hydrogel baseplate used in this study was easier to peel off from the skin than the dissolving baseplate. In vitro release studies demonstrated that the release of amphotericin B from the drug loading PLGA tips lasts for a week. Antifungal tests of the inserted amphotericin B loaded PLGA tips revealed their antifungal effects against Candida albicans. The MN8 did not dissolve, leaving no viscous residue but absorbed water and disintegrated after immersion into water. The hybrid PLGA-tipped microneedle system will be ideal for rapid implantation and sustained release of amphotericin B for dermal fungal infections. This hybrid patch design is a novel promising technology for delivering drug-eluting microimplants into the skin while ensuring easy and complete removal of the HFMB. It could have many potential applications in implantable intradermal drug delivery.


Assuntos
Sistemas de Liberação de Medicamentos , Hidrogéis , Administração Cutânea , Preparações de Ação Retardada , Agulhas , Pele
13.
Molecules ; 26(11)2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34200144

RESUMO

Natural products have been extensively used for treating a wide variety of disorders. In recent times, Brucine (BRU) as one of the natural medications extracted from seeds of nux vomica, was investigated for its anticancer activity. As far as we know, this is the first study on BRU anticancer activity against skin cancer. Thus, the rational of this work was implemented to develop, optimize and characterize the anticancer activity of BRU loaded ethosomal gel. Basically, thin film hydration method was used to formulate BRU ethosomal preparations, by means of Central composite design (CCD), which were operated to construct (32) factorial design. Two independent variables were designated (phospholipid percentage and ethanol percentage) with three responses (vesicular size, encapsulation efficiency and flux). Based on the desirability function, one formula was selected and incorporated into HPMC gel base to develop BRU loaded ethosomal gel. The fabricated gel was assessed for all physical characterization. In-vitro release investigation, ex-vivo permeation and MTT calorimetric assay were performed. BRU loaded ethosomal gel exhibited acceptable values for the characterization parameters which stand proper for topical application. In-vitro release investigation was efficiently prolonged for 6 h. The flux from BRU loaded ethosome was enhanced screening optimum SSTF value. Finally, in-vitro cytotoxicity study proved that BRU loaded ethosomal gel significantly improved the anticancer activity of the drug against A375 human melanoma cell lines. Substantially, the investigation proposed a strong motivation for further study of the lately developed BRU loaded ethosomal gel as a prospective therapeutic strategy for melanoma treatment.


Assuntos
Etanol/química , Géis/química , Pele/efeitos dos fármacos , Estricnina/análogos & derivados , Administração Cutânea , Animais , Géis/administração & dosagem , Masculino , Fosfolipídeos/química , Ratos , Ratos Wistar , Absorção Cutânea/efeitos dos fármacos , Neoplasias Cutâneas/tratamento farmacológico , Estricnina/administração & dosagem , Estricnina/química
14.
Biomater Sci ; 9(16): 5612-5625, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34254062

RESUMO

This study reports that the use of low-frequency sonophoresis (LFS) in combination with sponge Haliclona sp. spicules (SHS), referred to as cSoSp (combined Sonophoresis and Spicules), can enhance the transdermal drug delivery in a synergistic manner. The topical application of cSoSp in vitro significantly enhanced the skin absorption of Fluorescent-Dextrans (4000 Da, FD-4K), a model drug of low-molecular-weight heparin (LMWH). The utilization of cSoSp dramatically increased the transdermal flux of FD-4K (188.6 ± 93.7 ng cm-2 h-1) compared to LFS (5.8 ± 3.1 ng cm-2 h-1) and SHS (3.2 ± 1.2 ng cm-2 h-1) among others. The mechanism of action of cSoSp could be attributed to the synergism between plenty of long-lasting nano-channels created by SHS and the disorders of SC lipids made by shock waves of LFS, which improves the homogeneity of the cavitation effects. Furthermore, LMWH (3000 Da) was transdermally delivered by using cSoSp to treat both superficial venous thrombosis (SVT) and deep venous thrombosis (DVT) in the marginal ear vein of rabbits with a good therapeutic effect. Furthermore, skin irritation and toxicity studies using guinea pigs indicated that cSoSp was nonirritating without any morphological changes in the keratinocytes. cSoSp offers a promising strategy to enhance the transdermal delivery of hydrophilic macromolecules such as heparin.


Assuntos
Heparina , Trombose Venosa , Administração Cutânea , Animais , Cobaias , Heparina/metabolismo , Heparina de Baixo Peso Molecular , Coelhos , Pele/metabolismo , Absorção Cutânea , Trombose Venosa/tratamento farmacológico , Trombose Venosa/metabolismo
15.
Eur J Pharm Sci ; 165: 105935, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34284096

RESUMO

To overcome the poor solubility, skin irritation, and low permeability of azelaic acid (AZA) existed on the marketed formulations, a co-drug principle via matrine (MAT) was adopted to prepare anti-acne dissolving microneedles (DMNs). The formula was optimized according to the solubility and antibacterial activity of novel ionic salt. The results indicated solubilization of AZA could be achieved at a molar ratio between AZA and MAT was 1:1. Meanwhile, synergistic antibacterial and anti-irritative properties were acquired. The matrix materials were composed of sodium carboxymethyl cellulose (CMC), polyvinylpyrrolidone (PVP), and trehalose. And drug loadings of AZA and MAT in DMNs were 201.88 ± 4.81 µg and 259.71 ± 1.72 µg, respectively. After insertion into porcine skin for 10 h, the cumulative permeability of AZA and MAT were 68.16% ± 3.79% and 57.37 ± 5.17%, respectively, while just 4.13 ± 0.39% (p < 0.01) was detected for commercially available AZA gel. In vitro antibacterial experiment, bacteriostatic rates of DMNs were all above 95% for Staphylococcus aureus, Staphylococcus epidermidis, and Propionibacterium acnes. Besides, DMNs exhibited no cytotoxicity and skin irritation. In conclusion, combination between AZA and MAT addressed shortcomings of AZA, and made it easier, safer, and more effective in acne treatment.


Assuntos
Acne Vulgar , Pele , Administração Cutânea , Alcaloides , Animais , Ácidos Dicarboxílicos , Quinolizinas , Suínos
16.
Clin Drug Investig ; 41(8): 675-683, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34213758

RESUMO

BACKGROUND: Distressing symptoms are prevalent in patients with idiopathic Parkinson's disease, yet little is known about symptom burden and subsequent pharmacological management at the end of life. Additionally, when oral administration of antiparkinsonian medications is no longer possible in dying patients, it is becoming common place to initiate transdermal rotigotine, despite a paucity of evidence to guide dosing. OBJECTIVES: To assess: (1) symptom prevalence from the use of anticipatory medicines in patients with idiopathic Parkinson's disease, (2) the prescribing of antiparkinsonian medication at the end of life; and (3) the accuracy of conversion from oral antiparkinsonian medicines to transdermal rotigotine and any associations between rotigotine dosing and end-of-life symptoms. METHODS: A retrospective case review was performed. One hundred consecutive patients with idiopathic Parkinson's disease who died during an inpatient admission at a UK teaching hospital were assessed. RESULTS: The most prevalent terminal symptoms were excess respiratory secretions (58%), pain (52%), agitation (51%) and fever (23%). The majority of patients were converted to transdermal rotigotine (90%). Patients converted to a higher than equivalent dose of rotigotine were more likely to be agitated (p < 0.05), whilst those converted to a lower than equivalent dose were less likely to develop excess respiratory secretions (p < 0.05). The prevalence of pain did not differ according to rotigotine dosing. CONCLUSIONS: This study highlights for the first time use of anticipatory medications at the end of life in patients with idiopathic Parkinson's disease and the prevalence of terminal symptoms. It also demonstrates the widespread use of rotigotine patches, and that lower than equivalent doses may be better tolerated.


Assuntos
Doença de Parkinson , Administração Cutânea , Morte , Agonistas de Dopamina , Humanos , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/epidemiologia , Prevalência , Estudos Retrospectivos , Tetra-Hidronaftalenos/uso terapêutico , Tiofenos , Adesivo Transdérmico
17.
Int J Mol Sci ; 22(12)2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34200719

RESUMO

The potential of bacterial cellulose as a carrier for the transport of ibuprofen (a typical example of non-steroidal anti-inflammatory drugs) through the skin was investigated. Ibuprofen and its amino acid ester salts-loaded BC membranes were prepared through a simple methodology and characterized in terms of structure and morphology. Two salts of amino acid isopropyl esters were used in the research, namely L-valine isopropyl ester ibuprofenate ([ValOiPr][IBU]) and L-leucine isopropyl ester ibuprofenate ([LeuOiPr][IBU]). [LeuOiPr][IBU] is a new compound; therefore, it has been fully characterized and its identity confirmed. For all membranes obtained the surface morphology, tensile mechanical properties, active compound dissolution assays, and permeation and skin accumulation studies of API (active pharmaceutical ingredient) were determined. The obtained membranes were very homogeneous. In vitro diffusion studies with Franz cells were conducted using pig epidermal membranes, and showed that the incorporation of ibuprofen in BC membranes provided lower permeation rates to those obtained with amino acids ester salts of ibuprofen. This release profile together with the ease of application and the simple preparation and assembly of the drug-loaded membranes indicates the enormous potentialities of using BC membranes for transdermal application of ibuprofen in the form of amino acid ester salts.


Assuntos
Aminoácidos/química , Anti-Inflamatórios não Esteroides/farmacologia , Celulose/química , Ésteres/química , Ibuprofeno/farmacologia , Absorção Cutânea/efeitos dos fármacos , Pele/efeitos dos fármacos , Administração Cutânea , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Bactérias/metabolismo , Sistemas de Liberação de Medicamentos , Ibuprofeno/administração & dosagem , Ibuprofeno/química , Suínos
19.
Drug Dev Ind Pharm ; 47(6): 963-976, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34283682

RESUMO

OBJECTIVE: Parkinson disease (PD) is a chronic disorder of central nervous system mainly affecting the motor systems. The drug of choice to treat PD is Rasagiline Mesylate (RM) and it belongs to BCS class III drug. The objective of the present study was the preparation of transdermal drug delivery system for RM. Several permeation enhancers were screened to be included in the formulation. To achieve desired flux a new strategy was developed by including in-house prepared CTC to enhance the permeation of RM. METHODS: The CTC was prepared by reaction between chitosan and thioglycolicacid, characterized by determining physical properties and applying analytical tools. Seven permeation enhancers with different mechanisms were screened. The transdermal patches were prepared with chitosan along with permeation enhancer IPM, various proportions of CTC and evaluated for physical and permeation studies. The optimized transdermal patch was obtained by two factors and three responses to obtain the design space and further evaluated for pharmacokinetic studies. RESULTS: The results of the present study confirmed the formation of CTC, IPM was best permeation enhancer among all. The presence of CTC in the formulations significantly improved the permeation of RM to achieve desired steady-state flux. The relative bioavailability of optimized transdermal patch was determined and it was observed that improved bioavailability as compared to marketed conventional tablets. CONCLUSION: The study was concluded that CTC has significant influence on permeation enhancing ability of IPM.


Assuntos
Quitosana , Adesivo Transdérmico , Administração Cutânea , Disponibilidade Biológica , Quitosana/metabolismo , Indanos , Mesilatos , Pele/metabolismo , Comprimidos/metabolismo , Tioglicolatos
20.
Langmuir ; 37(30): 8971-8977, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34242506

RESUMO

The stratum corneum (SC) covers the outer surface of the skin and prevents the permeation of unwanted materials; however, the SC barrier also inhibits the desired permeation of active pharmaceutical ingredients (APIs). Therefore, the development of a novel method to enhance the permeation of APIs through the skin has been the focus of significant attention. Palmitoyl-glycine-histidine (Pal-GH)-comprising palmitic acid, glycine, and histidine-can be co-assembled with various additives to form a thixotropic hydrogel. Self-assembled Pal-GH enhances the permeation of ivermectin through the skin; however, the permeation mechanism is unclear and has not yet been discussed in detail. In the present study, the self-assembled structure of Pal-GH was analyzed using X-rays and infrared, and its permeation enhancement effect was verified. There was a correlation between the amount of Pal-GH in the skin and permeation enhancement, suggesting the involvement of the Pal-GH molecule. The presence of Pal-GH in the skin was confirmed by liquid chromatography-mass spectrometry and fluorescence labeling (labeling with Thioflavin T, a fluorescent dye that responds to ß-sheets). The self-assembled Pal-GH permeated the SC without disrupting its organization. However, the structure of the Pal-GH caused changes to the lipid organization of the SC. The findings indicated that self-assembled Pal-GH is an effective permeation enhancer for transdermal delivery and does not induce skin irritation.


Assuntos
Histidina , Absorção Cutânea , Administração Cutânea , Glicina , Permeabilidade , Pele/metabolismo
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