New Perspectives in Drug Delivery Systems for the Treatment of Tuberculosis.

BACKGROUND: Tuberculosis is a chronic respiratory disease caused by Mycobacterium tuberculosis. The common treatment regimens of tuberculosis are lengthy with adverse side effects, low patient compliance, and antimicrobial resistance. Drug delivery systems (DDSs) can overcome these limitations. OBJECTIVE: This review aims to summarize the latest DDSs for the treatment of tuberculosis. In the first section, the main pharmacokinetic and pharmacodynamic challenges posed by the innate properties of the drugs are put forth. The second section elaborates on the use of DDS to overcome the disadvantages of the current treatment of tuberculosis. CONCLUSION: We reviewed research articles published in the last 10 years. DDSs can improve the physicochemical properties of anti-tuberculosis drugs, improving solubility, stability, and bioavailability, with better control of drug release and can target alveolar macrophages. However, more pre-clinical studies and robust bio-relevant analyses are needed for DDSs to become a feasible option to treat patients and attract investors.

Synthesis of Eudragit® L100-coated chitosan-based nanoparticles for oral enoxaparin delivery.

Enoxaparin is an effective biological molecule for prevention and treatment of coagulation disorders. However, it is poorly absorbed in the gastrointestinal tract. In this study, we developed an Eudragit® L100 coated chitosan core shell nanoparticles for enoxaparin oral delivery (Eud/CS/Enox NPs) through a completely eco-friendly method without employing any high-energy homogenizer technique and any organic solvents. Spherical nanocarriers were successfully prepared with particle size lower than 300 nm, polydispersity index about 0.12 and zeta potential higher than +25 mV, entrapment efficiency greater than 95% and the in vitro release behavior confirms the good colloidal stability and the successful Eudragit® L100 coating process demonstrated by negligible cumulative enoxaparin release (<10%) when the particles are submitted to simulated gastric fluid conditions. Finally, we demonstrated that the core-shell structure of the particle influenced the drug release mechanism of the formulations, indicating the presence of the Eudragit® L100 on the surface of the particles. These results suggested that enteric-coating approach and drug delivery nanotechnology can be successfully explored as potential tools for oral delivery of enoxaparin.

Eco-friendly synthesis of phthalate angico gum towards nanoparticles engineering using Quality by Design (QbD) approach.

We developed a new hydrophobic polymer based on angico gum (AG), and we produced new nanoparticles to expand the applications of natural polysaccharides in nanomedicine. Phthalate angico gum (PAG) was characterized by 1H NMR, FTIR, elementary analysis, solubility, XRD, and TG. PAG was a hydrophobic and semi-crystalline material, a relevant characteristic for drug delivery system applications. As a proof of concept, nevirapine (NVP) was selected for nanoparticles development. Plackett-Burman's experimental design was used to understand the influence of several factors in nanoparticles production. PAG proved to be a versatile material for producing nanoparticles with different characteristics. Optimized nanoparticles were produced using desirability parameters. NVP-loaded PAG nanoparticles formulation showed 202.1 nm of particle size, 0.23 of PDI, -17.1 of zeta potential, 69.8 of encapsulation efficiency, and promoted modified drug release for 8 h. Here we show that PAG presents as a promising biopolymer for drug delivery systems.

Drug Delivery Systems on Leprosy Therapy: Moving Towards Eradication?

Leprosy disease remains an important public health issue as it is still endemic in several countries. Mycobacterium leprae, the causative agent of leprosy, presents tropism for cells of the reticuloendothelial and peripheral nervous system. Current multidrug therapy consists of clofazimine, dapsone and rifampicin. Despite significant improvements in leprosy treatment, in most programs, successful completion of the therapy is still sub-optimal. Drug resistance has emerged in some countries. This review discusses the status of leprosy disease worldwide, providing information regarding infectious agents, clinical manifestations, diagnosis, actual treatment and future perspectives and strategies on targets for an efficient targeted delivery therapy.

Solvent-free synthesis of acetylated cashew gum for oral delivery system of insulin.

Cashew gum (CG) is a biopolymer that presents a favorable chemical environment for structural modifications, which leads to more stable and resistant colloidal systems. The gum was subjected to an acetylation reaction using a fast, simple, solvent-free and low cost methodology. The derivative was characterized by infrared and NMR spectroscopy, elemental analysis, coefficient of solubility and zeta potential. The modified biopolymer was used as a platform for drug delivery systems using insulin as a model drug. Nanoparticles were developed through the technique of polyelectrolytic complexation and were characterized by size, surface charge, entrapment efficiency and gastrointestinal release profile. The nanoparticles presented size of 460 nm with a 52.5% efficiency of entrapment of insulin and the electrostatic stabilization was suggested by the zeta potential of + 30.6 mV. Sustained release of insulin was observed for up to 24 h. The results showed that acetylated cashew gum (ACG) presented potential as a vehicle for sustained oral insulin release.

Desenvolvimento e validação de metodologias analíticas para quantificação de um derivado tiofênico em sistemas microemulsionados / Development and validation of analytical methodologies for measurement of a tiophene derivative in microemulsion systems

O presente trabalho teve por objetivo validar métodos por espectrofotometria UV-Vis e por CLAE para a análise quantitativa de um derivado do tiofeno, o 2-[(3,4-dicloro-benzilideno)-amino]-5,6-diidro-4H-ciclopen-ta[b]tiofeno-3-carbonitrila (5CN05) e aplicá-los no doseamento da molécula contida em microemulsões, Os métodos propostos foram validados conforme a Resolução 899/2003 da Agência Nacional de Vigilância Sanitária (ANVISA), O comprimento de onda de máxima absorção do fármaco 5CN05 foi detectado em λ max= 387nm, O método espectrofotométrico validado mostrou-se seletivo, apresentando linearidade na faixa de 3 a 16 µg.mL-1, coeficiente de correlação (r) igual a 0,9998 e limites de detecção e quantificação de 0,12 µg.mL-1 e 0,41 µg.mL-1, respectivamente, Para o método CLAE, observou-se linearidade na faixa de 0,1 a 3,0 µg.mL-1, r = 0,99915, limites de detecção e quantificação de 0,07 µg.mL-1 e 0,10 µg.mL-1 respectivamente, Para ambos os métodos, os parâmetros precisão, exatidão e robustez mostraram-se adequados para o uso pretendido, As metodologias propostas podem ser seguramente aplicadas para quantificação do 5CN05 em produtos farmacêuticos como microemulsões...

This study aims to validate methods of Uv-Vis) and HPLC for quantitative determination of a thiophene derivative, 2 - [(3,4-dichloro -benzylidene)-amino] -5,6-dihydro-4H-cyclopentyl-ta [b] thiophene-3- carbonitrile referred in this study as 5CN05, and apply them to quantify the 5CN05 in microemulsions. The proposed methods were validated according to the Resolution RE 899/2003 of the National Health Surveillance Agency (ANVISA). The 5CN05 was detected by UV-Vis at λ max= 387nm. The validated UVVis UVVis method proved to be selective, showing linearity in the range of 3-16 µg.mL-1, correlation coefficient (r) of 0.9998 and limits of detection and quantification of 0.12 µg.mL-1 and 0.41 µg.mL-1 respectively. For the CLAE method the linearity was observed in the range 0.1 to 3.0 µg.mL-1, r = 0.99915, limits of detection and quantification of 0.07 µg.mL-1 and 0.10 µg.mL-1 respectively. For both UV-Vis and CLAE methods, the precision parameters, accuracy and robustness were adequate for the intended use. The proposed methodologies can be safely applied to quantify the 5CN05 in pharmaceutical microemulsions products...