Polymeric Films Loaded with Vitamin E and Aloe vera

Burns are serious traumas related to skin damage, causing extreme pain and possibly death. Natural drugs such as Aloe vera and vitamin E have been demonstrated to be beneficial in formulations for wound healing. The aim of this work is to develop and evaluate polymeric films containing Aloe vera and vitamin E to treat wounds caused by burns. Polymeric films containing different quantities of sodium alginate and polyvinyl alcohol (PVA) were characterized for their mechanical properties and drug release. The polymeric films, which were produced, were thin, flexible, resistant, and suitable for application on damaged skin, such as in burn wounds. Around 30% of vitamin E acetate was released from the polymeric films within 12 hours. The in vivo experiments with tape stripping indicated an effective accumulation in the stratum corneum when compared to a commercial cream containing the same quantity of vitamin E acetate. Vitamin E acetate was found in higher quantities in the deep layers of the stratum corneum when the film formulation was applied. The results obtained show that the bioadhesive films containing vitamin E acetate and Aloe vera could be an innovative therapeutic system for the treatment of burns

A Liposome-Micelle-Hybrid (LMH) Oral Delivery System for Poorly Water-Soluble Drugs: Enhancing Solubilisation and Intestinal Transport

A novel liposome-micelle-hybrid (LMH) carrier system was developed as a superior oral drug delivery platform compared to conventional liposome or micelle formulations. The optimal LMH system was engineered by encapsulating TPGS micelles in the aqueous core of liposomes and its efficacy for oral delivery was demonstrated using lovastatin (LOV) as a model poorly soluble drug with P-gp (permeability glycoprotein) limited intestinal absorption. LOV-LMH was characterised as unilamellar, spherical vesicles encapsulating micellar structures within the interior aqueous core and showing an average diameter below 200 nm. LMH demonstrated enhanced drug loading, water apparent solubility and extended/controlled release of LOV compared to conventional liposomes and micelles. LMH exhibited enhanced LOV absorption and transportation in a Caco-2 cell monolayer model of the intestine by inhibiting the P-gp transporter system compared to free LOV. The LMH system is a promising novel oral delivery approach for enhancing bioavailability of poorly water-soluble drugs, especially those presenting P-gp effluxes limited absorption

Chitosan-Coated Nanoparticles: Effect of Chitosan Molecular Weight on Nasal Transmucosal Delivery

Drug delivery to the brain represents a challenge, especially in the therapy of central nervous system malignancies. Simvastatin (SVT), as with other statins, has shown potential anticancer properties that are difficult to exploit in the central nervous system (CNS). In the present work the physico⁻chemical, mucoadhesive, and permeability-enhancing properties of simvastatin-loaded poly-ε-caprolactone nanocapsules coated with chitosan for nose-to-brain administration were investigated. Lipid-core nanocapsules coated with chitosan (LNCchit) of different molecular weight (MW) were prepared by a novel one-pot technique, and characterized for particle size, surface charge, particle number density, morphology, drug encapsulation efficiency, interaction between surface nanocapsules with mucin, drug release, and permeability across two nasal mucosa models. Results show that all formulations presented adequate particle sizes (below 220 nm), positive surface charge, narrow droplet size distribution (PDI < 0.2), and high encapsulation efficiency. Nanocapsules presented controlled drug release and mucoadhesive properties that are dependent on the MW of the coating chitosan. The results of permeation across the RPMI 2650 human nasal cell line evidenced that LNCchit increased the permeation of SVT. In particular, the amount of SVT that permeated after 4 hr for nanocapsules coated with low-MW chitosan, high-MW chitosan, and control SVT was 13.9 ± 0.8 μg, 9.2 ± 1.2 µg, and 1.4 ± 0.2 µg, respectively. These results were confirmed by SVT ex vivo permeation across rabbit nasal mucosa. This study highlighted the suitability of LNCchit as a promising strategy for the administration of simvastatin for a nose-to-brain approach for the therapy of brain tumors

Attainment of O/W nano-emulsion with grape seed oil and olive oil added of octylmethoxycinnamate and study of the antioxidant potential and the sun protection of the emulsions

A nanotecnologia é um fenômeno que se aplica a praticamente todos os etores da ciência, sendo que na área cosmética o elevado investimento neste campo tem reforçado a idéia de que os produtos nanotecnológicos proporcionam vantagens reais aos consumidores. A crescente exigência do consumidor e os avanços no conhecimento sobre a obtenção e estabilidade dos sistemas dispersos viabilizam o desenvolvimento de veículos diferenciados como, por exemplo, nanoemulsões, que além da inerente estabilidade, apresentam aspecto sensorial agradável, alta capacidade de espalhabilidade e hidratação. Existem dois métodos de obtenção das nanoemulsões: empregando baixa ou alta energia de emulsificação. O uso de óleos vegetais em produtos cosméticos tem sido intensamente valorizado, baseando-se no conceito de que são seguros e biocompatíveis. Podem ser utilizados em cosméticos com sua funcionalidade potencializada, sendo estes ricos em ácidos graxos essenciais, Ômega 3, Ômega 6, Ômega 9, fitosteróis, vitamina C e polifenóis (antocianinas). Alguns óleos vegetais têm poder antioxidante comprovado, previnem as oxidações biológicas e reduzem a formação de radicais livres responsáveis pelo dano celular, grande vilão do envelhecimento e das doenças crônico-degenerativas, como o câncer. Atualmente é crescente o interesse da pesquisa sobre a atividade de substâncias capazes de proteger a pele contra a radiação ultravioleta de forma eficaz. O metoxicinamato de octila é um filtro solar químico capaz de proteger a pele e conferir um fator de proteção solar ao produto final. Nesse estudo foram desenvolvidas nanoemulsões à base de óleos de oliva e semente de uva aditivadas de metoxicinamato de octila. Após a análise da estabilidade físico-química e caracterização das formulações, foram avaliados o potencial antioxidante das formulações, o efeito de proteção solar do sistema, liberação e permeação do ativo e uma possível irritação ocular das formulações que se mantiveram estáveis.Nanotechnology is a phenomenon that is applied to mainly all sectors of science. In the cosmetic area the high investment has strengthened the idea that nanotechnology products offer real advantages to consumers. The growing demand of consumers and the advances in the knowledge about production and stability of dispersed systems enable the development of differentiated vehicles such as nano-emulsions, which besides their inherent stability, they have pleasant sensorial aspect, high spread ability and hydration power. There are two methods of nano-emulsions attainment: low or high energy of emulsifying. The use of vegetable oils in cosmetic products has had enormous and growing value, based in the concept that they are safe and biocompatible. They can be used in cosmetics with their functionality improved, being rich in essential fatty acids, Omega 3, Omega 6, Omega 9, phytosterols, vitamin C and polyphenols (anthocyanins). Some vegetable oils have proved antioxidant power, as well as they avoid biological oxidation and decrease the forming of free radicals responsible for cellular damage, which are the causes of aging and disease such as cancer. Nowadays, the interest of research about the activity of substances that protect the skin against ultraviolet irradiation in an efficacious way is growing. Octylmethoxycinnamate is a chemical sunscreen that can protect skin and offers sun protection factor to final product. In this study nano-emulsions were developed using olive oil and grape seed oil added with octylmethoxycinnamate. After the analysis of the physic-chemical stability and formulation characterization, the antioxidant potential of formulations, the effect of sun protection of the system, delivery and permeation of the active agent, and a possible ocular irritation of the stable formulations were evaluated

Strategies for the development of dressings for burn wounds based on hyaluronic acid / aloe vera / vitamin E

As queimaduras constituem, nas diferentes idades, uma importante causa de morte por trauma, tanto em países desenvolvidos quanto naqueles em desenvolvimento. Apesar dos recentes avanços no desenvolvimento de substâncias ativas, os produtos naturais como plantas e minerais continuam sendo a maior fonte para obtenção de moléculas para os mais diversos fins. Neste trabalho, foi proposta a primeira aplicação de uma mistura de substâncias naturais – Ácido hialurônico; Aloe vera; acetato de tocoferol - para a preparação curativos para o tratamento de feridas de queimaduras. A primeira etapa do trabalho constituiu no desenvolvimento de micropartículas de quitosana contendo vitamina E e Aloe vera e de um método analítico para a quantificação do acetato de tocoferol nas micropartículas de quitosana. O método se mostrou linear, especifico e reprodutível, foi também realizado ensaios de fotoestabilidade, onde o acetato de tocoferol microencapsulada se mostrou mais estável que o acetato de tocoferol em pó comercial. Na segunda etapa, consistiu no desenvolvimento de um gel termorreversível e para isto fez-se a avaliação reológica do gel de poloxamer 407, determinando-se que o gel contendo 18% de poloxamer possui temperatura sol-gel de 32 °C e que quando se adiciona as micropartículas esta temperatura diminui para 30 °C. O gel demonstrou propriedades pseudo-plásticas e baixa viscosidade. Na etapa seguinte, foram desenvolvidas com sucesso microparticulas contendo aloe vera/acetato de tocoferol. Diversas análises microscópicas foram efetuadas para caracterizá-las e um método in vivo para avaliação da permeação das partículas através da radiação gama foi desenvolvido. Avaliou-se também o poder cicatrizante do gel contendo as micropartículas e este apresentou um poder cicatrizante maior do que quando usado somente o gel sem as micrpartículas. Na quarta etapa, desenvolveu-se filmes poliméricos de hialuronato, contendo aloe vera e acetato de tocoferol, avaliando-se as suas propriedades mecânicas e morfológicas e testes de liberação comparando-os com um creme comercial contendo a mesma concentração de acetato de tocoferol. O filme apresentou uma liberação lenta, quando comparada ao creme que não liberação o fármaco e no teste de tape stripping foi possível observar que o acetato de tocoferol contido no filme permeava até as camadas mais profundas do estrato córneo em comparação ao creme comercial com a mesma quantidade de acetato de tocoferol. Na quinta e última etapa, foram desenvolvidas nanopartículas lipídicas contendo acetato de tocoferol, sendo estas caracterizadas por técnicas diversas. As nanopartículas apresentaram tamanho de partícula e polidispersão adequadas para uso tópico e cinética de liberação do acetato de tocoferol monoexponencial e tempo de meia- vida de 881 horas. Quando incorporadas em um filme polimérico de hialuronato, as mesmas apresentam liberação lenta quando comparadas a filmes de hialuronato contendo acetato de tocoferol livre e também propriedade oclusiva maior.The burns are in different ages an important cause of dead, both developed country as in undeveloped country. In despite of many studies discovery different substances the natural products like plants and minerals remain the main source to obtain different molecules to various purposes. In this work, we present in the first time a mixture of natural substances like Hyaluronic acid, Aloe vera and tocopherol acetate, to prepare different dressings to treat burn wounds. The first step was the development of chitosan micrparticles with tocopherol acetate and Aloe vera and an analytical method to quantify the tocopherol acetate in chitosan microparticles. The method showed linear, specific and reproducible, was also performed the photostability studies where the tocopherol acetate microparticulate presented more stable than the tocopherol acetate in a commercial power. The second step was the development of a thermorresible gel and for this and it became the rheological evaluation of poloxamer 407 gel, determined that the gel containing 18% of poloxamer has the sol-gel temperature equal 32 °C and when added the chitosan microparticles this temperature decreases for 30 °C. the gel demonstrated characteristics pseudo-plastic and low viscosity. In the next step, we developed chitosan microparticles containing Aloe vera/tocopherol acetate. Different microscopy analyses were used to characterize the microparticles and an in vivo method was used to evaluate the microparticles permeation through the gamma scintigraphy. Was also evaluated the healing power of the gel containing the microparticles and this presented a healing power better than used the gel without the microparticles. The fourth stage we developed polymeric films with hialuronate/ Aloe vera/ tocopherol acetate we evaluated the mechanics and morphologic properties and release tests compared with a commercial cream with the same quantity of tocopherol acetate. The film presented a slow release compared with the commercial cream that did not release tocopherol acetate. The tape stripping test it was possible observed that the tocopherol acetate in polymeric films permeated to the deeper layers of the stratum corneum compared with the commercial cream with the same quantities of tocopherol acetate. In the last stage were developed lipid nanoparticles with tocopherol acetate and characterized by different techniques. The nanoparticles presented particle size and polidispersion index adequate to used in topic application and the tocopherol acetate kinetic release monoexponencial and the half life equal a 881 hours. When incorporate the particles in polymeric films the particles presenting slow release compared with polymeric films containing tocopherol acetate free and the occlusion properties better. In conclusion it was possible develop different dressings to treatment of burn wounds

Loco-regional administration of nanomedicines for the treatment of lung cancer

Lung cancer poses one of the most significant challenges to modern medicine, killing thousands every year. Current therapy involves surgical resection supplemented with chemotherapy and radiotherapy due to high rates of relapse. Shortcomings of currently available chemotherapy protocols include unacceptably high levels of systemic toxicity and low accumulation of drug at the tumor site. Loco-regional delivery of nanocarriers loaded with anticancer agents has the potential to significantly increase efficacy, while minimizing systemic toxicity to anticancer agents. Local drug administration at the tumor site using nanoparticulate drug delivery systems can reduce systemic toxicities observed with intravenously administered anticancer drugs. In addition, this approach presents an opportunity for sustained delivery of anticancer drug over an extended period of time. Herein, the progress in the development of locally administered nanomedicines for the treatment of lung cancer is reviewed. Administration by inhalation, intratumoral injection and means of direct in situ application are discussed, the benefits and drawbacks of each modality are explored

Polymeric Films Loaded with Vitamin E and Aloe vera for Topical Application in the Treatment of Burn Wounds

Burns are serious traumas related to skin damage, causing extreme pain and possibly death. Natural drugs such as Aloe vera and vitamin E have been demonstrated to be beneficial in formulations for wound healing. The aim of this work is to develop and evaluate polymeric films containing Aloe vera and vitamin E to treat wounds caused by burns. Polymeric films containing different quantities of sodium alginate and polyvinyl alcohol (PVA) were characterized for their mechanical properties and drug release. The polymeric films, which were produced, were thin, flexible, resistant, and suitable for application on damaged skin, such as in burn wounds. Around 30% of vitamin E acetate was released from the polymeric films within 12 hours. The in vivo experiments with tape stripping indicated an effective accumulation in the stratum corneum when compared to a commercial cream containing the same quantity of vitamin E acetate. Vitamin E acetate was found in higher quantities in the deep layers of the stratum corneum when the film formulation was applied. The results obtained show that the bioadhesive films containing vitamin E acetate and Aloe vera could be an innovative therapeutic system for the treatment of burns

Formulation and characterization of poloxamer 407® : thermoreversible gel containing polymeric microparticles and hyaluronic acid

The influence of the composition and preparation method on the sol–gel transition temperature (Tsol–gel) and rheological response of poloxamer-based formulations was determined. Manual and more complex mechanical stirring were found to provide similar results. In addition, a linear dependence of Tsol–gel on the poloxamer content was observed in the range of concentrations analyzed, and a Poloxamer 407® concentration of 18% was selected. The addition of hyaluronic acid did not lead to significant changes in the Tsol–gel values. In contrast, the addition of microparticles caused a reduction in Tsol–gel without a significant reduction in gel strength, and pseudoplastic characteristics were observed, indicating that a thermoreversible gel was obtained with a rheology suitable for application in the treatment of burn wounds

Nanoemulsion-Enabled Oral Delivery of Novel Anticancer ω-3 Fatty Acid Derivatives

Lipid-based drugs are emerging as an interesting class of novel anticancer drugs with the potential to target specific cancer cell metabolic pathways linked to their proliferation and invasiveness. In particular, ω-3 polyunsaturated fatty acids (PUFA) derivatives such as epoxides and their bioisosteres have demonstrated the potential to suppress growth and promote apoptosis in triple-negative human breast cancer cells MDA-MB-231. In this study, 16-(4'-chloro-3'-trifluorophenyl)carbamoylamino]hexadecanoic acid (ClFPh-CHA), an anticancer lipid derived from ω-3,17,18-epoxyeicosanoic acid, was formulated as a stable nanoemulsion with size around 150 nm and narrow droplet size distribution (PDI < 0.200) through phase-inversion emulsification process followed by high pressure homogenization in view of an oral administration. The ClFPh-CHA-loaded nanoemulsions were able to significantly decrease the relative tumor volume in mice bearing an intramammary tumor xenograft at all doses tested (2.5, 10 and 40 mg/kg) after 32 days of daily oral administration. Furthermore, absolute tumor weight was decreased to 50% of untreated control at 10 and 40 mg/kg, while intraperitoneal administration could achieve a significant reduction only at the highest dose of 40 mg/kg. Results suggest that oral administration of ClFPh-CHA formulated as a nanoemulsion has a sufficient bioavailability to provide an anticancer effect in mice and that the activity is at least equal if not superior to that obtained by a conventional parenteral administration of equivalent doses of the same drug