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1.
Eur J Pharm Biopharm ; 124: 55-62, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29258912

RESUMO

Sugar fatty acid esters are an interesting class of non-ionic, biocompatible and biodegradable sugar-based surfactants, recently emerged as a valid alternative to the traditional commonly employed (e.g. polysorbates and polyethylene glycol derivatives). By varying the polar head (carbohydrate moiety) and the hydrophobic tail (fatty acid), surfactants with different physico-chemical characteristics can be easily prepared. While many research papers have focused on sucrose derivatives, relatively few studies have been carried out on lactose-based surfactants. In this work, we present the synthesis and the physico-chemical characterization of lactose oleate. The new derivative was obtained by enzymatic mono-esterification of lactose with oleic acid. Thermal, surface, and aggregation properties of the surfactant were studied in detail and the cytotoxicity profile was investigated by MTS and LDH assays on intestinal Caco-2 monolayers. Transepithelial electrical resistance (TEER) measurements on Caco-2 cells showed a transient and reversible effect on the tight junctions opening, which correlates with the increased permeability of 4 kDa fluorescein-labelled dextran (as model for macromolecular drugs) in a concentration dependent manner. Moreover, lactose oleate displayed a satisfactory antimicrobial activity over a range of Gram-positive and Gram-negative bacteria. Overall, the obtained results are promising for a further development of lactose oleate as an intestinal absorption enhancer and/or an alternative biodegradable preservative for pharmaceutical and food applications.


Assuntos
Materiais Biocompatíveis , Absorção Intestinal/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Lactose/farmacologia , Ácidos Oleicos/farmacologia , Conservantes Farmacêuticos/farmacologia , Tensoativos/farmacologia , Bactérias/efeitos dos fármacos , Bactérias/crescimento & desenvolvimento , Células CACO-2 , Varredura Diferencial de Calorimetria , Sobrevivência Celular/efeitos dos fármacos , Composição de Medicamentos , Difusão Dinâmica da Luz , Impedância Elétrica , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Humanos , Mucosa Intestinal/metabolismo , Intestinos/patologia , Lactose/análogos & derivados , Lactose/síntese química , Lactose/toxicidade , Testes de Sensibilidade Microbiana , Ácidos Oleicos/síntese química , Ácidos Oleicos/toxicidade , Permeabilidade , Conservantes Farmacêuticos/síntese química , Conservantes Farmacêuticos/toxicidade , Propriedades de Superfície , Tensoativos/síntese química , Tensoativos/toxicidade , Tecnologia Farmacêutica/métodos , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/metabolismo , Junções Íntimas/patologia
2.
Curr Drug Deliv ; 13(5): 673-81, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26674199

RESUMO

BACKGROUND: Particles from Gas Saturated Solution (PGSS) is an emergent method that employs supercritical carbon dioxide (scCO2) to produce microparticles. It is suitable for encapsulating biologically active compounds including therapeutic peptides and proteins. Poly(lactide acid) (PLA) and/or poly(lactic-coglycolic acid) (PLGA) are the most commonly used materials in PGSS, due to their good processability in scCO2. Previous studies demonstrated that the properties of the microparticles can be modulated by adding polyethylene glycol (PEG) or tri-block PEGylated copolymers. OBJECTIVE: In the present work, the effect of the addition of biodegradable PEGylated di-block copolymers on the physical properties and drug release performance of microparticles prepared by PGSS technique was evaluated. METHOD: mPEG5kDa-P(L)LA and mPEG5kDa-P(L)LGA with similar molecular weights were synthesized and their behaviour, when exposed to supercritical CO2, was investigated. Different microparticle formulations, composed of a high (81%) or low (9%) percentage of the synthesized copolymers were prepared and compared in terms of particle size distribution, morphology, yield and protein release. Drug release studies were performed using bovine serum albumin (BSA) as a model protein. RESULTS: PEGylated copolymers showed good processability in PGSS without significant changes to the physical properties of the microparticles. However, the addition of PEG exerted a modulating effect on the microparticle drug dissolution behaviour, increasing the rate of BSA release as a function of its content in the formulation. CONCLUSION: This study demonstrated the feasibility of producing microparticles by using PEGylated di-block copolymers through a PGSS technique at mild operating conditions (low operating pressure and temperature).


Assuntos
Cromatografia com Fluido Supercrítico , Portadores de Fármacos , Nanopartículas , Nanotecnologia/métodos , Poliésteres/síntese química , Polietilenoglicóis/síntese química , Soroalbumina Bovina/química , Tecnologia Farmacêutica/métodos , Dióxido de Carbono/química , Composição de Medicamentos , Estudos de Viabilidade , Cinética , Tamanho da Partícula , Pressão , Solubilidade , Temperatura
3.
Curr Drug Deliv ; 13(4): 565-73, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26051184

RESUMO

BACKGROUND: Efficacy of melatonin in treating sleep disorders has been demonstrated in numerous studies. Being with short half-life, melatonin needs to be formulated in extended-release tablets to prevent the fast drop of its plasma concentration. However, an attempt to mimic melatonin natural plasma levels during night time is challenging. METHODS: In this work, Artificial Neural Networks (ANNs) were used to optimize melatonin release from hydrophilic polymer matrices. Twenty-seven different tablet formulations with different amounts of hydroxypropyl methylcellulose, xanthan gum and Carbopol®974P NF were prepared and subjected to drug release studies. Using dissolution test data as inputs for ANN designed by Visual Basic programming language, the ideal number of neurons in the hidden layer was determined trial and error methodology to guarantee the best performance of constructed ANN. RESULTS: Results showed that the ANN with nine neurons in the hidden layer had the best results. ANN was examined to check its predictability and then used to determine the best formula that can mimic the release of melatonin from a marketed brand using similarity fit factor. CONCLUSION: This work shows the possibility of using ANN to optimize the composition of prolonged-release melatonin tablets having dissolution profile desired.


Assuntos
Preparações de Ação Retardada , Melatonina/química , Redes Neurais de Computação , Química Farmacêutica , Melatonina/administração & dosagem , Solubilidade , Comprimidos
4.
Int J Pharm ; 468(1-2): 250-7, 2014 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-24746690

RESUMO

A series of biodegradable P(L)LA-PEG1.5 kDa-P(L)LA copolymers have been synthesized and compared as processing aid versus Poloxamer 407 (PEO-PPO-PEO), in the formulation of protein encapsulated microparticles, using supercritical carbon dioxide (scCO2). Bovine serum albumin (BSA) loaded microcarriers were prepared applying the particles from the gas saturated solutions (PGSS) technique using scCO2 and thus, avoiding the standard practice of organic solvent encapsulation. Four triblock copolymers were synthesized and characterized, particularly in terms of thermal properties and behaviour when exposed to scCO2. The effects of the inclusion of these copolymers in the formulation of poly(α-hydroxy acids) based microparticles - e.g. poly(D,L-lactic-co-glycolic acid) (PLGA) and poly(D,L-lactide) (PLA) - were analysed in terms of yield, particle size, morphology and drug release. The use of P(L)LA-PEG1.5 kDa-P(L)LA triblock copolymers were found to increase the yield of the PGSS-based process and to decrease the size of the microparticles produced, in comparison with the formulation containing the Poloxamer 407. Moreover the microparticles formulated with the triblock copolymers possessing the higher hydrophobic character were able to maintain a controlled drug release profile.


Assuntos
Cromatografia com Fluido Supercrítico , Portadores de Fármacos , Ácido Láctico/síntese química , Polietilenoglicóis/síntese química , Polímeros/síntese química , Soroalbumina Bovina/química , Tecnologia Farmacêutica/métodos , Dióxido de Carbono , Química Farmacêutica , Preparações de Ação Retardada , Gases , Interações Hidrofóbicas e Hidrofílicas , Cinética , Poloxâmero/síntese química , Poliésteres , Ácido Poliglicólico/síntese química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Porosidade , Solubilidade , Viscosidade
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