These results demonstrate that the hexagonal phase nanodispersion is effective in improving the topical delivery of peptides without causing skin irritation.
Inclusion complexes of rifampicin (RP) were prepared with hydroxypropyl-β-cyclodextrin (HPβCD). The aqueous solubility of RP increased linearly with cyclodextrin concentration in all rangeof the solubility diagram. The data was analyzed using the framework of Higuchi and Connors. The stability constant (K) values for RP/HPβCD complex at pH 6.9 were 18 and 120-125 M -1 for ionic strength 0.01 and 0.18M, respectively. The analysis of the chemical shift data of 1 H and 15 N for free RP and RP/HPβCD inclusion complex reveal that only peaks of the side chain related to the piperazine ring of RP change substantially, probably due to interaction of this region of RP molecule with the hydrophobic core of HPβCD. We also postulated the optimized structure of RP/ HPβCD inclusion complex using molecular modelling study. We found that the postulated structure was in agreement with 1 H and 13 C-NMR and 15 N-NMR spectra.
proporções molares de 1:1 e 1:2 foram analisados por microscopia eletrônica de varredura (SEM). O perfil de dissolução do BBAP e dos complexos de inclusões foram também avaliados durante 6 horas. Por microscopia eletrônica de varredura foi possível observar os complexos de inclusões formados entre BBAP e β-CD por co-evaporação nas proporções molares de 1:1 e 1:2. Como previamente detectado pela caracterização físico-química, na mistura física não se observou a presença de complexo de inclusão. Os estudos de dissolução mostraram que os complexos de inclusões 1:1 e 1:2 liberaram, respectivamente 49.07 ± 1.48 e 40.26 ± 3.90% de BBAP durante 6 horas. BBAP na forma livre foi menos solúvel que os complexos de inclusões e atingiu 9.00 ± 0.75% de dissolução. Os ensaios de citotoxicidade em macrófagos J774 e em uma linhagem de células fibroblásticas de pulmão (V79) indicaram que o BBAP não exibiu efeito tóxico adicional quando complexado com β-CD. Entretanto, os complexos de inclusões foram menos tóxicos para células V79 que BBAP na forma livre. Os complexos de inclusões BBAP/β-CD foram mais efetivos (CIM) que o composto livre em várias cepas de micobactérias. Resultados semelhantes foram observados sobre M. tuberculosis H37Rv intracelular para os complexos de inclusões BBAP/β-CD e rifampicina, uma droga antituberculose de primeira linha.Inclusion complexes and physical mixtures of isomeric mixture of E/Z (50:50) of 3-(4'-bromo-[1,1'-biphenyl]-4-yl)-3-(4-bromophenyl)-N,N-dimethyl-2-propen-1-amine (BBAP) and β-cyclodextrin (β-CD) in the molar proportion of 1:1 and 1:2 were analyzed by scanning electron microscopy. The dissolution behavior of BBAP and of the inclusion complexes were also evaluated for six hours. By scanning electron microscopy (SEM), it was possible to observe an inclusion complex formed between BBAP and β-CD by co-evaporation, either in the molar proportion of 1:1 or 1:2. In the physical mixtures, no complex was observed as previously detected by physicochemical analysis. The dissolution studies showed that the inclusion complexes BBAP/β-CD 1:1 and 1:2 released respectively 49.07 ± 1.48 and 40.26 ± 3.90% of BBAP during six hours. Free BBAP was less soluble than the inclusion complex and reached 9.00 ± 0.75% of dissolution. Biological assays, such as cytotoxicity to J774 macrophages and to a permanent lung fibroblast cell line (V79), indicated that the BBAP does not exhibit any additional toxic effect with the β-CD complexes. However, the complexes were less cytotoxic to V79 cells than the free form. The BBAP/β-CD inclusion complexes were more effective (MIC) than the free compound on several mycobacteria strains. Similar behavior was observed for BBAP/β-CD complexes and rifampicin, a front-line antitubercular drug, on M. tuberculosis H37Rv growing inside J774 macrophages.
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