Doxycycline release and antibacterial activity from PMMA/PEO electrospun fiber mats

Abstract Objective: To investigate the use of polymethyl methacrylate (PMMA) electrospun fiber mats containing different amounts of polyethylene oxide (PEO) as a doxycycline delivery system and to test antibacterial activity against an oral pathogen. Methodology: PMMA powders or PEO (mol wt 200 Kd) (10,20,30% w/w/) were dissolved in N, N-dimethylformamide (DMF) to obtain a final polymer concentration of 15% in DMF (w/v). 2% Doxycycline monohydrate was added to the solutions and submitted to vortex mixing. The solution was transferred to a plastic syringe and fit into a nanofiber electrospinning unit. The parameters applied were: voltage at 17.2 kV; distance of 20 cm between the needle tip and the collector plate; target speed at 2 m/min; and transverse speed at 1cm/min. Syringe pump speed was 0.15 mm/min. The drug release analysis was performed by removing aliquots of the drug-containing solution (in PBS) at specific periods. Doxycycline release was quantified using RP-HPLC. Fiber mats from all groups had their antibacterial action tested against S. mutans based on inhibition halos formed around the specimens. The experiments were performed in triplicate. Gravimetric analysis at specific periods was performed to determine any polymer loss. Morphological characterization of the electrospun fibers was completed under an optical microscope followed by SEM analysis. Results: The addition of PEO to the PMMA fibers did not affect the appearance and diameter of fibers. However, increasing the %PEO caused higher doxycycline release in the first 24 h. Fibers containing 30% PEO showed statistically significant higher release when compared with the other groups. Doxycycline released from the fibers containing 20% or 30% of PEO showed effective against S. mutans. Conclusion: The incorporation of PEO at 20% and 30% into PMMA fiber mat resulted in effective drug release systems, with detected antibacterial activity against S. mutans.

Comparative study of the stability of free and modified papain incorporated in topical formulations

Papain is an enzyme used in topical formulations as a proteolytic debriding agent for the treatment of open, extensive wounds and burnings. It is also employed as an enhancer for cutaneous permeation of active compounds, chemical peeling and as a progressive depilatory agent. The stability of formulations containing enzymes is not easy. In this research, papain was modified with polyethylene glycol in order to increase the stability of the formulations. The comparative Normal Stability Testing of the topical formulations containing unmodified and modified papain showed that the modified variety presented with a differentiated profile under the adopted temperature conditions (5.0 ± 1.0 °C; 22.0 ± 2.0 °C; 40.0 ± 2.0 °C). The most suitable condition for non-modified papain were 5.0 ± 1.0 °C and, for modified papain, they were 22.0 ± 2.0 °C. These results confirmed the higher stability of modified papain compared to free papain, as well as its potential to be applied in topical formulations.

A papaína é uma enzima utilizada em formulações tópicas como agente proteolítico debridante no tratamento de lesões abertas de grande extensão e queimaduras. É, também, empregada na pele íntegra como agente promotor da permeação cutânea de princípios ativos, peeling químico e como agente depilatório progressivo. A estabilidade de formulações contendo enzimas não é facilmente alcançada. No presente trabalho realizou-se a modificação da enzima com polietilenoglicol, visando maior estabilidade das formulações. A realização do Teste Estabilidade Normal comparativo entre as formulações contendo as formas da enzima não modificada e modificada demonstrou que a última apresentou um perfil de estabilidade diferenciado, nas diferentes condições (5,0 ± 1,0 °C; 22,0 ± 2,0 °C; 40,0 ± 2,0 °C). A condição de 5,0 ± 1,0 °C foi a mais adequada para a formulação contendo papaína não modificada enquanto a 22,0 ± 2,0 °C foi indicada para aquela contendo a forma modificada. Estes resultados confirmaram o aumento da estabilidade da papaína modificada comparada com a livre e seu potencial de aplicação em formulações de uso tópico.

Improvement of solubility and dissolution rate of indomethacin by solid dispersions in gelucire 50/13 and PEG4000

The aim of this study was to prepare and characterize solid dispersions of water insoluble non steroidal anti-inflammatory drug, indomethacin [IND], with polyethylene glycol 4000 [PEG4000] and Gelucire 50/13 [Gelu.] for enhancing the dissolution rate of the drug. The solid dispersions [SDs] were prepared by hot melting method at 1:1, 1:2 and 1:4 drug to polymer ratios. Scanning electron microscopy [SEM], X-ray powder diffractometry [XRD] and differential scanning calorimetry [DSC] were used to examine the physical state of the drug. Furthermore, the solubility and the dissolution rate of the drug in its different systems were explored. The data from the XRD showed that the drug was still detectable in its solid state in all SDs of IND-Gelu and disappeared in case of higher ratio of IND-PEG4000. DSC thermograms showed the significant change in melting peak of the IND when prepared as SDs suggesting the change in crystallinity of IND. The highest ratio of the polymer [1:4] enhanced the drug solubility about 4 folds or 3.5 folds in case of SDs of IND-PEG or IND-Gelu., respectively. An increased dissolution rate of IND at pH 1.2 and 7.4 was observed when the drug was dispersed in these carriers in form of physical mixtures [PMs] or SDs. IND released faster from the SDs than from the pure crystalline drug or the PMs. The dissolution rate of IND from its PMs or SDs increased with an increasing amount of polymer

Alteraçöes da permeabilidade intestinal em crianças / Alterations of the intestinal permeability in children

É apresentada uma revisäo atualizada sobre permeabilidade intestinal, enfocando as vias de permeabilidade, as substâncias-testes e as técnicas mais comumente empregadas para estudo e quantificaçäo da mesma. Säo também destacadas algumas afecçöes pediátricas associadas com anormalidade da permeabilidade intestinal

Effect of polyethylene glycols on the rheological characteristics of macloid dispersions

The effect of polyethylene glycols 400, 1500 and 4000 on the rheological characteristics of Macaloid dispersions was studied. The rheological study included investigation of the phenomena of consistency, thixotropic breakdown and structural recovery in the stationary state. The consistency of Macaloid dispersions increases in presence of PEG 400 and PEG 1500. This increase is, generally, in direct proportion to the glycol concentration. In the case of PEG 4000, the consistency of Macaloid dispersions is slightly decreased in presence of the low concentrations of the glycol and is slightly affected at the high ones. These effects were interpreted as sum of the adsorption of the glycols between the clay lamellae, the thickening effect of the glycols towards the continuous phase of the dispersions and the dehydrating effect of the glycols. The rate of increase consistency of Macaloid dispersions, on aging is generally increased in presence of low concentrations of the glycols which might indicate a slow adsorption of the glycols. This rate is, however, decreased at high glycol concentrations, which might be a result of the dehydrating effect of the glycols. The thixotropic breakdown of Macaloid dispersions, induced by increasing rate of shear, is generally increased in presence of PEG 400 and PEG 1500 and decreased by PEG 4000. On the other hand, the thixotropic breakdown by shearing is affected differently by the different concentrations of the glycols. The rate of structural recovery is affected differently by the different concentrations of polyethylene glycols. However, all systems attain complete structural recovery after a rest of an hour