Long-term anti-cancer implants inhibiting the activity of tumor growth in animal models / 生物医学工程学杂志

This study was aimed to establish rat bladder tumor animal models to investigate the in viva antitumor effect of polyanhydride-pirarubicin (PAD-THP), a long-lasting anti-cancer implant, in the bladder tumor of animal models. The model of bladder cancer was set up with N-butly-N-(4 hydroxybutyl) nitrosamine (BBN) feeding into rats. The PAD-THP long-acting anti-cancer implants containing the drugs and the same dose of the THP naked drug were placed under the bladder mucosa of bladder tumor model in vivo. The pirarubicin plasma concentration was measured with high performance liquid chromatography (HPLC) detection in vivo. The effective drug concentration and lasting period were observed and compared in the animal bodies. The tumor sizes were measured before and after the treatment. The in viva antitumor effects were analyzed and compared. The results showed that more significant antitumor effect of PAD-THP implants on the local drug release characteristics were presented compared with that of the same dose of THP bare drug group and there were significant differences (P<0. 05) between the two methods. All the results indicated that the PAD-THP anti-cancer implants in the postoperative local treatment of bladder tumors would show prosperous in the future for clinical application.

The study of absorbable sustained-release implants and animal experiments to prevent recurrence of bladder cancer / 生物医学工程学杂志

This paper aims to prepare polyanhydride-Pirarubicin dose long-acting sustained-release implants for the treatment of bladder cancer and for the prevention of postoperative recurrence of bladder cancer. Pirarubicin hydrochloride (THP) and polyanhydride, in accordance with a certain proportion, were fully mixed in the agate morta and dissolved in dichloromethane, and then were cast into a film within a mold put in the dryer set at 4 degrees C. Each tablet implanted contained 5.0 mg of THP. Polyanhydride-pirarubicin sustained-release was implanted into the bladder mucosa of the rabbits, and blood and urine samples were taken at different times after the operation. The THP drug concentrations in urine and blood were determined with high-performance liquid chromatography. The THP concentration in urine was significantly higher than the THP concentration in plasma. The drug concentration in urine reached (92.5 +/- 7.4) microg/L at 250 d time after the operation. Polyanhydride-pirarubicin implants possess long-acting sustained-release level dynamics in the body. It can maintain a stable long-term drug release and can be expected to last a year and can effectively prevent recurrence of bladder cancer. The present experiments proved that the implants with sustained-release drug treatment are expected to be useful in the clinical application in prevention of bladder cancer recurrence.

Investigation of polyanhydride-glucan as stem cell carriers / 生物医学工程学杂志

<p><b>UNLABELLED</b>The purpose of this study with regard to the effects of polyanhydride--three-dimensional vector-glucan material on the fetal liver stem cell adhesion and proliferation was to find a new carrier. The methods of two-step collagenase perfusion digestion and liquid Percoll discontinuous density gradient centrifugation were used for the separation of fetal liver stem cells. The fetal liver stem cells were selected and cultivated in the polyanhydride-three-dimensional vector-glucan material. Inverted microscope was used to observe cell adhesion and growth status. Also performed were: Calculation of the rate of cell adhesion; MTT assay of the cells in each group absorbance value (OD value); collecting and counting the cells on the carrier scaffold. Then the cell carriers histological sections (HE staining) were observed. On the 7th day of cell culture, the cells were subjected to immunofluorescence staining and flow cytometry.</p><p><b>RESULTS</b>polyanhydride-three-dimensional vector-glucan promoted liver stem cells growth and adhesion. There were active functions of the liver stem cells within carrier materials. In the three-dimensional surface and the internal culture of liver stem cell, proliferation was sustained. After 40 days, the polyanhydride co-culture-three-dimensional vector-glucan showed no sign of toxicity to stem cells. Human fetal liver stem cells attached to the polyanhydride--three-dimensional vector-glucan stent. The cell proliferation went on well and exhibited sustained expression of markers; 7 days training led up to an increase of 19.7 percent in the number of cells. Conclusively, polyanhydride-three-dimensional vector-glucan can be used for promoting the proliferation of liver stem cells, and liver stem cells can be used as vectors in liver tissue engineering.</p>

Preparation of gentamicin sulfate-polyanhydride sustained-release beads and in vitro bacteriostatic activity studies / 生物医学工程学杂志

Drug slow release in osteomyelitis treatment is an important biomedical problem, to prepare the high effect drug sustained-release bead is the sticking point. A sustained-release bead system consisting of gentamicin sulfate in biodegradable poly(dimer acid-tetradecandioic acid) copolymer [P(DA-TA), WDA: WTA= 50: 50] is prepared by melt casting which may be useful in osteomyelitis treatment. The stability at room temperature and the in vitro release profile in distilling water, in 0.9% saline buffer and in 0.1 mol/LpH7.4 PBS at 37 degrees C of the bead are determined, the drug release behavior in vitro follows the first order release kinetics and Peppas release kinetics equation. In vitro bacteriostatic activity studies demonstrated that the beads possessed desired bacteriostatic activity and lasted for 50 days for Staphylococcus aureus and Escherichia coli, which are common bacteria for infections in bone. All the above suggest that the biodegradable sustained-release beads may be a new treatment device for osteomyelitis treatment.

Hidrogéis de PVP e blendas de PVP/polianidridos como potenciais curativos para feridas crônicas / PVP hydrogels and PVP/Polyanhydride blends as potential materials for chronic wounds dressings

Hidrogéis compreendem uma importante classe de materiais poliméricos adequados à aplicação como curativos de feridas e queimaduras. A estrutura tridimensional hidrofílica dos hidrogéis permite que estes mantenham a umidade ideal no leito das feridas, absorvam o exsudato e não causem danos ao novo tecido durante as trocas dos curativos. No caso dos hidrogéis, essas trocas podem ser menos frequentes. Além disso, curativos que auxiliem na remoção de tecidos necrosados e ainda sejam capazes de oferecer tratamentos extras que acelerem o processo de cicatrização são desejáveis. Este trabalho apresenta a produção de materiais à base de hidrogel capazes de auxiliar neste processo de diferentes maneiras. Primeiramente, são apresentados hidrogéis formados a partir de nanofibras de poli(N-vinil-2-pirrolidona) (PVP) produzidas por eletrofiação, seguido da reticulação através da utilização de radiação UV-C ou reação de Fenton. A utilização da eletrofiação como técnica auxiliar na formação dos hidrogéis permitiu o controle da porosidade através da formação de fibras de diferentes diâmetros. A evidência de tal propriedade foi constatada através da produção de materiais que apresentam diferentes perfis de liberação da proteína modelo albumina de soro bovino (BSA). O hidrogel de PVP nanoestruturado foi capaz de liberar e manter a atividade da colagenase, uma importante enzima aplicada no tratamento de feridas via desbridamento enzimático, durante as 48 horas em que foi avaliado. Além disso, hidrogéis bactericidas nanoestruturados foram produzidos a partir de nanocompósitos de PVP e nanopartículas de prata (AgNP) produzidos por eletrofiação. Esses hidrogéis apresentaram propriedades térmicas semelhantes aos hidrogéis sem AgNP, diminuindo, contudo, a sua capacidade de intumescimento. Esses hidrogéis mostraram-se ativos contra bactérias gram-positivas e gram-negativas a partir de 100 ppm de AgNPs. Adicionalmente, foi estudada a formação de um hidrogel modelo composto PVP/AgNP/Imidazol, almejando-se a produção de um material bactericida-fungicida a base de hidrogel. Este hidrogel apresentou atividade conta três espécies de Candida a partir de 500 ppm de imidazol no material. Embora exista a formação de um complexo estável entre AgNP e Imidazol, cálculos teóricos e a constatação da atividade fungicida corroboram com o fato de que derivados imidazólicos podem ser liberados a partir deste hidrogel híbrido. A produção de hidrogéis físicos compostos por blendas de PVP/Polianidridos sintetizados a partir de derivados de hidroxicinamatos e ácido salicílico, capazes de liberar moléculas de interesse biológico quando parcialmente degradados hidroliticamente, também é descrita neste trabalho. Os resultados indicam que interações hidrofóbicas entre a PVP e os polianidridos sintetizados podem ser responsáveis pela formação dos hidrogéis físicos e pela miscibilidade das blendas produzidas. Os hidrogéis físicos de PVP/Polianidridos foram obtidos na forma de filmes por evaporação do solvente. Micro- e nanofibras também foram obtidas por eletrofiação. Desta maneira, o presente trabalho contribui com o desenvolvimento de uma geração de curativos multifuncionais aplicados no tratamento de feridas crônicas e queimaduras

Hydrogels comprise an important class of polymeric materials that finds application as wound and burn dressings. The hydrophilic three-dimensional structure of hydrogels helps to provide the ideal humidity at the wound bed, to remove exsudates and to prevent damages to the new tissue during dressing substitution. Furthermore, these wound dressings are able to remove necrotic tissues and, therefore, capable to offer extra treatments that would benefit the healing processes. This work describes the production of hydrogel based materials that are able to act in wound healing by different ways. First, it is presented hydrogels composed of poly(N-vinyl-2-pyrrolidone) (PVP) nanofibers produced by electrospinning, followed by its crosslinking using UV-C radiation or Fenton reaction. The use of electrospinning in the hydrogel formation allowed porosity control by obtaining fibers of different diameters. This was evidenced by achieving materials that present different release profiles of the model protein bovine serum albumin (BSA). The nanostructured PVP hydrogel was capable of releasing and maintaining collagenase activity during 48 hour of evaluation. This is an important enzyme that find application in wound healing based on enzymatic debridement. Moreover, nanostructured bactericidal hydrogels were produced from PVP and silver nanoparticles (AgNP) composite through electrospinning, resulting in hydrogels with thermal properties similar to those hydrogels without AgNP, decreasing its swelling ability. These hydrogels were active against gram-positives and gram-negatives bacteria starting from 100 ppm of AgNP. In addition, the production of a model hydrogel composed by PVP/AgNP/Imidazole was investigated, aiming at a bactericidal-fungicidal hydrogel based material. This hydrogel was active against three Candida having 500 ppm of imidazole into the structure. In spite of the formation of a stable complex between AgNP and imidazole, theoretic calculations and the observed fungicidal activity corroborate with the fact that imidazoles derivatives can be released from this hybrid hydrogel. Physical hydrogels composed of PVP/Polyanhydrides blends were synthesized from hydroxycinammates derivatives and salicylic acid. These materials which were capable of releasing molecules with biological potential upon hydrolysis, are also described in this work. The results indicate that hydrophobic interactions between PVP and the synthesized polyanhydrides could be responsible for the hydrogel formation and blend miscibility as well. PVP/Polyanhydride physical hydrogels were obtained from cast films. Micro- and nanofibers were also obtained by electrospinning. Thus, the present work contributes with the development of the new generation of smart dressings for wound and burn healing