RESUMO
Hexagonal liquid crystals and supramolecular polymers from meglumine-based supra-amphiphiles were developed as drug delivery systems to be applied on the skin. The influence of fatty acid unsaturation on the structure and mechanical properties was evaluated. Moreover, we have investigated the system biocompatibility and how the type of water could influence its bioadhesive properties. Meglumine-oleic acid (MEG-OA) was arranged as hexagonal liquid crystals at 30-70â¯wt% water content, probably due to its curvature and increased water solubility. Meglumine-stearic acid (MEG-SA) at 10-80â¯wt% water content self-assembled as a lamellar polymeric network, which can be explained by the low mobility of MEG-SA in water due to hydrophobic interactions between fatty acid chains and H-bonds between meglumine and water molecules. Both systems have shown suitable mechanical parameters and biocompatibility, making them potential candidates to encapsulate therapeutic molecules for skin delivery. Moreover, a strong positive correlation between the amount of unfrozen bound water in meglumine-based systems and the bioadhesion properties was observed. This work shows that a better understanding of the physicochemical properties of a drug delivery system is extremely important for the correlation with the desired biological response and, thus, improve the product performance for biomedical applications.
Assuntos
Sistemas de Liberação de Medicamentos , Meglumina/química , Pele/química , Tensoativos/química , Água/química , Adesão Celular , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Meglumina/síntese química , Meglumina/farmacologia , Tamanho da Partícula , Relação Estrutura-Atividade , Propriedades de Superfície , Tensoativos/síntese química , Tensoativos/farmacologia , ViscosidadeRESUMO
Citral (CIT) is a monoterpene formed by the geranial and neral stereoisomers. CIT is the major compound of Cymbopogon citratus essential oil, commonly known as "lemongrass", and has demonstrated potential antihyperalgesic, anti-nociceptive and anti-inflammatory effects. However, CIT shows high volatility, low solubility in water and consequent low bioavailability, which limits its use. Therefore, the aim of this study was to evaluate cell viability, anti-hyperalgesic and anti-inflammatory effects of inclusion complexes of CIT on ß-cyclodextrin (ß-CD) and hydroxypropyl-ß-cyclodextrin (HP-ß-CD). Initially, physical mixture (PM) and freeze-dried inclusion (FD) complexes of CIT/ß-CD and CIT/HP-ß-CD were obtained in the molar ratio (1:1). The samples were characterized by DSC, TG/DTG, FT-IR, XRD, SEM and the complexation efficiency were performed by HPLC. Cell viability assay was performed by rezasurin reduction technique in J774 macrophages cell line. The motor activity through rota rod apparatus, mechanical hyperalgesia and pleurisy induced by carrageenan were evaluated in mice. The complexation of CIT was evidenced with ß-CD and HP-ß-CD by the characterization techniques analyzed. The complexation efficiency of CIT/ß-CD and CIT/HP-ß-CD were 78.6% and 71.7%, respectively. The CIT, CIT/ß-CD and CIT/HP-ß-CD showed cell viability in macrophages and did not interfere in the motor activity of mice. Besides that, the samples demonstrated antihyperalgesic and anti-inflammatory activity due to the reduction in total leukocytes and TNF-α levels. However, CIT/ß-CD has better pharmacological effects among the three samples evaluated. Therefore, CIT/ß-CD has potential for the development of products to treat inflammatory and pain reactions.
Assuntos
2-Hidroxipropil-beta-Ciclodextrina/farmacologia , Anti-Inflamatórios/farmacologia , Modelos Animais de Doenças , Hiperalgesia/tratamento farmacológico , Inflamação/tratamento farmacológico , Monoterpenos/farmacologia , beta-Ciclodextrinas/farmacologia , Monoterpenos Acíclicos , Animais , Comportamento Animal/efeitos dos fármacos , Carragenina/toxicidade , Quimioterapia Combinada , Hiperalgesia/induzido quimicamente , Hiperalgesia/patologia , Inflamação/induzido quimicamente , Inflamação/patologia , Masculino , CamundongosRESUMO
This study explored the transition of lamellar-type liquid crystal (LLC) to biocompatible oil-in-water nanoemulsions able to modify benznidazole (BNZ) release and target the drug to cells infected with the T. cruzi parasite. Three cosolvents (2methylpyrrolidone [NMP], polyethylene glycol [POL], and propylene glycol [PRO] were tested to induce the transition of anisotropic LLC systems to isotropic nanoemulsions. Mixtures of soy phosphatidylcholine with sodium oleate stabilized the dispersions of medium chain triglyceride in water. Rheological measurements, polarized microscopy, and small angle X-ray scattering demonstrated that there is a phase transition from LLC to desired nanoemulsions. These small and narrow droplet-sized nanocarriers exhibited some advantages and promising features, such as the enhanced BNZ aqueous solubility and slow drug release rate. In vitro cell biocompatibility of formulations was assessed in the Vero E6 and SiHa cell lines. Drug-loaded nanoemulsions inhibited the epimastigote growth of the T. cruzi parasite (IC50 0.208⯱â¯0.052⯵gâ¯mL-1) and reduced its infective life form trypomastigote (IC50 0.392⯱â¯0.107⯵gâ¯mL-1). The oil-in-water nanoemulsions were demonstrated as promising biocompatible liquid drug delivery systems capable of improving the BNZ trypanocidal activity for the treatment of Chagas disease.
Assuntos
Sistemas de Liberação de Medicamentos , Nitroimidazóis/administração & dosagem , Tripanossomicidas/administração & dosagem , Trypanosoma cruzi/efeitos dos fármacos , Animais , Linhagem Celular , Doença de Chagas/tratamento farmacológico , Química Farmacêutica/métodos , Chlorocebus aethiops , Preparações de Ação Retardada , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Emulsões , Humanos , Concentração Inibidora 50 , Cristais Líquidos , Nanoestruturas , Nitroimidazóis/química , Nitroimidazóis/farmacologia , Transição de Fase , Solubilidade , Solventes/química , Tripanossomicidas/química , Tripanossomicidas/farmacologia , Células VeroRESUMO
Previous studies reported low benznidazole (BNZ) loading in conventional emulsions due to the weak interaction of the drug with the most common oils used to produce foods or pharmaceuticals. In this study, we focused on how the type of surfactant, surfactant-to-oil ratio w/w (SOR) and oil-to-water ratio w/w (OWR) change the phase behavior of different lipid-based drug delivery systems (LBDDS) produced by emulsion phase inversion. The surfactant mixture composed of soy phosphatidylcholine and sodium oleate (1:7, w/w, hydrophilic lipophilic balance = 16) stabilized medium chain triglyceride in water. Ten formulations with the clear aspect or less turbid dispersions (five with the SOR ranging from 0.5 to 2.5 and five with the OWR from 0.06 to 0.4) were selected from the phase behavior diagram to assess structural features and drug-loading capacity. The rise in the SOR induced the formation of distinct lipid-based drug delivery systems (nanoemulsions and liquid crystal lamellar type) that were identified using rheological measurements and cross-polarized light microscopy images. Clear dispersions of small and narrow droplet-sized liquid-like nanoemulsions, Newtonian flow-type, were produced at SOR from 0.5 to 1.5 and OWR from 0.12 to 0.4, while clear liquid or gel-like liquid crystals were produced at SOR from 1.5 to 2.5. The BNZ loading was improved according to the composition and type of LBDDS produced, suggesting possible drug location among surfactant layers. The cell viability assays proved the biocompatibility for all of the prepared nanoemulsions at SOR less than 1.5 and liquid crystals at SOR less than 2.5, demonstrating their promising features for the oral or parenteral colloidal delivery systems containing benznidazole for Chagas disease treatment.
Assuntos
Materiais Biocompatíveis/química , Portadores de Fármacos/química , Nitroimidazóis/química , Animais , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Portadores de Fármacos/toxicidade , Difusão Dinâmica da Luz , Emulsões/química , Cristais Líquidos/química , Microscopia , Nanoestruturas/química , Nitroimidazóis/toxicidade , Óleos/química , Transição de Fase , Reologia , Tensoativos/química , Células Vero , Água/químicaRESUMO
The development of a controlled-release dosage form of zidovudine (AZT) is of crucial importance, in view of the pharmacokinetics of its toxic activity. A suitable drug delivery system could increase AZT bioavailability, reducing its dose-dependent side effects. In this study, systems composed of polyoxypropylene (5) polyoxyethylene (20) cetyl alcohol as surfactant (S), oleic acid as oil phase (O), and water (W) were developed, as possible AZT control release systems. They were characterized by polarized light microscopy (PLM), SAXS, and rheological analysis, followed by in vitro release assay. PLM and SAXS results indicated that the mixtures of S/O/W in the proportions 55/35/10 and 55/25/20 formed microemulsion (ME) systems, while 55/20/25 formed lamellar phase. The incorporation of AZT in these systems was greater than in water or oil; moreover, AZT incorporation did not significantly change the phase behavior of the mixtures. MEs behave as Newtonian fluids in flow rheological analysis and the lamellar phase as a pseudoplastic fluid. The release profile indicated that AZT could be released in a controlled manner, since an exponential pattern governs AZT diffusion, as demonstrated by the Weibull mathematical model. These systems are potential carriers for AZT and could have advantages over conventional pharmaceutical forms.