An injectable hydrogel/staple fiber composite for sustained release of CA4P and doxorubicin for combined chemotherapy of xenografted breast tumor in mice / 南方医科大学学报

OBJECTIVE@#To prepare an injectable hydrogel/staple fiber composite loaded with combretastain A-4 disodium phosphate (CA4P) and doxorubicin (DOX) and evaluate its antitumor efficacy via intratumoral injection.@*METHODS@#DOX-loaded PELA staple fibers (FDOX) were prepared using electro-spinning and cryo-cutting, and the drug distribution on the surface of the fibers was observed using a fluorescence microscope, and the encapsulation efficiency and loading capacity of FDOX were determined with a fluorospectro photometer. The fibers were then dispersed in CA4P-loaded PLGA-PEG-PLGA tri-block polymer solution at room temperature to obtain the hydrogel/staple fiber composite (GCA4P/FDOX). The thermo-sensitivity of this composite was determined by a test tube inverting method. An ultraviolet spectrophotometer and a fluorospectrophotometer were used to detect the release profile of CA4P and DOX, respectively. We observed in vivo gel formation of the composite after subcutaneous injection in mice. The in vitro cytotoxicity of GCA4P/FDOX composite in MCF-7 and 4T1 cells was assessed using cell Counting Kit-8 (CCK-8) reagent. In a mouse model bearing breast tumor 4T1 cell xenograft, we evaluated the antitumor efficacy of the composite by monitoring tumor growth within 30 days after intratumoral injection of the composite. HE staining, immunohistochemistry for Ki67 and immunofluorescence (TUNEL) assay were used for pathological examination of the tumor tissues 21 days after the treatments.@*RESULTS@#The average length of FDOX was 4.0±1.3 μm, and its drug loading capacity was (2.69±0.35)% with an encapsulation efficiency of (89.70±0.12)%. DOX was well distributed on the surface of the fibers. When the temperature increased to 37 ℃, the composite rapidly solidified to form a gel in vitro. Drug release behavior test showed that CA4P was completely released from the composite in 5 days and 87% of DOX was released in 30 days. After subcutaneous injection, the composite solidified rapidly without degradation at 24 h after injection. After incubation with GCA4P/FDOX for 72 h, only 30.6% of MCF-7 cells and 28.9% of 4T1 cells were viable. In the tumor-bearing mice, the tumor volume was 771.9±76.9 mm3 in GCA4P/FDOX treatment group at 30 days. Pathological examination revealed obvious necrosis of the tumor tissues and tumor cell apoptosis induced by intratumoral injection of G4A4P/FDOX.@*CONCLUSION@#As an efficient dual drug delivery system, this hydrogel/staple fiber composite provides a new strategy for local combined chemotherapy of solid tumors.

Design and evaluation of ocular hydrogel containing combination of ofloxacin and dexamethasone for the treatment of conjunctivitis

Abstract Conjunctivitis is an inflammation of the conjunctiva, which covers the white part of the eyeball. It can be caused by allergies, bacterial or viral infection. In situ hydrogels are three-dimensional hydrophilic cross-linked network of polymers. In situ hydrogel provided better therapeutic index when compared to conventional treatment. The present work describes the formulation and evaluation of ofloxacin and dexamethasone based on the concept of pH triggered in situ gelation. Carbopol 934p was used as the gelling agent in combination with HPMC, as a viscosity-enhancing agent, benzalkonium chloride as preservative, sodium chloride as tonicity adjusting agent. The prepared formulations were liquid at the low pH and underwent rapid transition into viscous gel at the pH of the tear fluid. Formulations were evaluated for various rheological, in vitro and in vivo release characteristics. Infrared spectroscopy studies showed that there were no interactions between the drug and polymers. Viscosity of the prepared hydrogels lies in the optimum range and drug was released up to 85 % as the end of 13 h. The prepared in situ hydrogel was sterile, non-irritant to the eye. The present study indicated that it is possible to develop safe and physiologically effective in situ hydrogel which is patient compliant.

Morphometric study of rat sciatic nerve recovery after three nerve repair techniques: epineural suture, polyethylene glycol hydrogel and fibrin sealant / Estudio morfométrico de la recuperación del nervio ciático de rata después de tres técnicas de reparación nerviosa: sutura epineural, hidrogel de polietilenglicol y sellante de fibrina

SUMMARY: The effectiveness of microsurgical technique has a direct impact on the recovery of the injured peripheral nerve. The aim of our study was to investigate the result of sciatic nerve regeneration in rats after complete neurotomy and after nerve repair techniques including: 1) epineural suture; 2) polyethylene glycol hydrogel (PEG) (DuraSeal); 3) fibrin sealant (Tisseel). The cross-section of distal sciatic nerve was studied at 14th, 30th and 60th days after nerve repair. Morphometry of myelinated nerve fibers in the distal stump of the sciatic nerve was performed. A significant increase in the number of myelinated nerve fibers was found, especially between 14 and 30 days. The density of myelinated nerve fibers in the distal stump at day 60 was significantly higher after using nerve repair technique including PEG and fibrin versus epineural suture (29.2 % and 32.1 % versus 21.5 %, P <0.05), and a higher level of remyelination of nerve fibers observed in the group with PEG. On day 60, complete elimination of PEG and fibrin sealant was not observed, encapsulation was found around the clusters of hydrogel. Thereby, three peripheral nerve repair techniques were equally effective, only with the use of PEG remyelination of nerve fibers was increasing.

RESUMEN: La efectividad de la técnica microquirúrgica tiene un impacto directo en la recuperación del nervio periférico lesionado. El objetivo de nuestro estudio fue investigar el resultado de la regeneración del nervio ciático en ratas después de una neurotomía completa y después de técnicas de reparación nerviosa que incluyeron: 1) sutura epineural; 2) hidrogel de polietilenglicol (PEG) (DuraSeal); 3) sellante de fibrina (Tisseel). La sección transversal del nervio ciático distal se estudió a los 14, 30 y 60 días después de la reparación del nervio. Se realizó la morfometría de fibras nerviosas mielinizadas en el muñón distal del nervio ciático. Se observó un aumento significativo en el número de fibras nerviosas mielinizadas, especialmente entre los 14 y 30 días. La densidad de las fibras nerviosas mielinizadas en el muñón distal en el día 60 fue significativamente mayor después de usar una técnica de reparación nerviosa que incluye PEG y fibrina en comparación con la sutura epineural (29,2 % y 32,1 % versus 21,5 %, P <0,05), y un mayor nivel de remielinización del nervio en fibras observadas en el grupo con PEG. El día 60, no se observó la eliminación completa de PEG y sellador de fibrina, se encontró encapsulación alrededor de los grupos de hidrogel. Por lo tanto, tres técnicas de reparación de nervios periféricos fueron igualmente efectivas, solo que aumentaba la remielinización de fibras nerviosas con PEG.

Percepção de enfermeiros acerca dos cuidados e a utilização de hidrogel em lesões por pressão / Perception of nurses about care and the use of hydrogel in pressure injuries

Resumo O estudo objetivou conhecer a percepção dos enfermeiros sobre a utilização do hidrogel em lesões por pressão. Trata-se de pesquisa com abordagem qualitativa realizada em uma instituição hospitalar pública de João Pessoa/Paraíba, onde a amostra foi composta por 17 enfermeiros atuantes no Centro de Terapia Intensiva, comissão de pele e sala vermelha. Os dados foram coletados através de uma entrevista utilizando um formulário semiestruturado, e a análise deu-se por meio da técnica de Análise de Conteúdo Temática. Foi revelado que existem fragilidades no que concerne aos conhecimentos dos enfermeiros em relação às lesões por pressão e à aplicação hidrogel. Observando-se a necessidade de realizar educação continuada nos serviços de saúde, com o objetivo de atenuar as limitações de conhecimentos dos enfermeiros no que se refere ao conceito, à classificação e às causas das lesões por pressão, bem como sobre a utilização do hidrogel.

Abstract The study aimed to know the perception of nurses about the use of hydrogels in pressure injuries. This is a research with a qualitative approach conducted in a public hospital in João Pessoa / Paraíba, where the sample consisted of 17 nurses working in the Intensive Care Center, skin committee and red room. Data were collected through an interview using a semi-structured form, and the analysis was performed using the Thematic Content Analysis. It was revealed that there are weaknesses regarding nurses' knowledge regarding pressure injuries and hydrogel application. Noting the need for continuing education in health services, with the aim of alleviating nurses' knowledge limitations regarding the concept, classification and causes of pressure injuries, as well as the use of hydrogel.

Resumen El estudio tuvo como objetivo conocer la percepción de las enfermeras sobre el uso de hidrogeles en lesiones por presión. Esta es una investigación con un enfoque cualitativo realizada en un hospital público en João Pessoa / Paraíba, donde la muestra consistió en 17 enfermeras que trabajan en el Centro de Cuidados Intensivos, el comité de la piel y la sala roja. Los datos fueron recolectados a través de una entrevista usando una forma semiestructurada, y el análisis se realizó usando la técnica de Análisis de Contenido Temático. Se reveló que existen debilidades con respecto al conocimiento de las enfermeras con respecto a las lesiones por presión y la aplicación de hidrogel. Observando la necesidad de educación continua en los servicios de salud, con el objetivo de aliviar las limitaciones de conocimiento de las enfermeras con respecto al concepto, clasificación y causas de las lesiones por presión, así como el uso de hidrogel.

Polyacrylamide Hydrogel (Bulkamid) in Female Patients of 80 or More Years with Urinary Incontinence

Introduction: To assess the effectiveness of polyacrylamide hydrogel (Bulkamid ®) in injection therapy for urinary incontinence in women of 80 or more years. Materials and Methods: Twenty consecutive women mean age 84.5 (range 80-87) with stress or mixed urinary incontinence were enrolled in this prospective study. All subjects were evaluated at baseline and re-evaluated 7 days, 6,12,18 and 24 months after treatment. A detailed clinical evaluation, physical examination, daily pad count, urodynamic investigation and evaluation of urethral mobility by trans-labial ultrasound were performed. Results: A statistically significant decrease in the number of pads was observed in the follow-up (p = 0.0002 after 24 months). Physical examination showed a statistically significant lack or reduced lost of urine with stress test (p = 0.0163 after 24 months). Urodynamic findings showed an increase of Valsalva leak point pressure, maximum urethral closure pressure and functional length. Maximum flow and post void residual were respectively observed to be significantly reduced and increased only after 7 days from injection therapy. Quality of life (QoL) assessed with the Incontinence Impact questionnaire short form (IIQ-7) showed a statistically significant improvement (p = 0.0001 after 24 months). Patient satisfaction assessed with the Visual Analogue Scale and Patient Global Impression of Improvement questionnaire respectively produced evaluation of “satisfied” and “much improved” even after 24 months. Conclusions: Polyacrylamide hydrogel (Bulkamid®) is an effective treatment with low morbility in patients of 80 or more years. .

Safety and efficiency of carboximethylcellulose hydrogel 2% in leg ulcers / Segurança e eficácia do hidrogel de carboximetilcelulose à 2% em úlceras de perna / Evaluación de la seguridad y eficacia del uso del hidrogel à 2% en ulceras de piernas

Objetivo: Avaliar a eficácia e a segurança do uso do hidrogel a 2%, manipulado na farmácia universitária, no tratamento de pacientes com úlceras de perna. Método: Estudo clínico, prospectivo, não controlado, incluindo 20 pacientes no período de janeiro a outubro de 2010. A avaliação da eficácia foi realizada através da redução e da alteração tecidual do leito da ferida. A segurança foi avaliada por observação e relato dos eventos adversos. Resultados: Os dados mostraram que 33,3% das lesões apresentaram cicatrização total. Quanto à segurança, apenas 2 pacientes apresentaram dor, aumento de exsudato e infecção da ferida como reações adversas possíveis, segundo o algoritmo de Naranjo, ao uso do hidrogel 2% como curativo. Conclusão: Os resultados permitem considerar que o hidrogel de CMC a 2% mostrou-se eficaz e seguro para o tratamento desse tipo de lesão.

Objective: The aim of this study is to assess the efficiency and safety on using hydrogel carboxymethylcellulose 2%, handled at university pharmacy in treatment of patients with leg ulcers. Method: A non-controlled prospective clinic study with 20 patients took place from January to October 2010. Results: The efficiency assessment was performed through the wound area reduction and wound bed tissue alteration; the safety was assessed through observation and report of adverse events. The data showed that 33.3% of the lesions presented total healing. Regarding the safety, only 2 patients reported pain, increase of the exudate and wound infection as possible adverse reaction to the use hydrogel as dressing, according to the Naranjo algorithm. Conclusion: The results let us consider that the hydrogel 2% can be considered efficient and safe for this type of lesion.

Objetivo: Es evaluar la eficacia y la seguridad del uso del Hidrogel 2%, manoseado en una farmacia docente, en el tratamiento de enfermos con úlceras de pierna. Método: El estudio clínico, no controlado, incluyó 20 pacientes en el periodo entre enero y octubre de 2010. Resultados: La evaluación de su eficacia fue comprobada por la reducción de la herida y de la alteración de la piel en su interior. La seguridad fue evaluada por observación y el relato de los eventos adversos. Los dados han evidenciados que 33,3% de las lesiones presentaron cicatrización total. Cuanto a la seguridad, solamente dos pacientes presentaron reacciones previsibles al uso del Hidrogel 2% como curativo. Conclusión: Se puede concluir que el Hidrogel 2% se muestra eficaz y seguro para el tratamiento de esto tipo de lesión.

2-hydroxyethyl methacrylate composite - polypropylene mesh for preventing peritoneal adhesions in female dogs / Compósito 2-hidroxietil dimetacrilato-tela de polipropileno para prevenção de aderências peritoneais em cadelas

PURPOSE: To evaluate whether the lining facing the visceral side of polypropylene mesh made with 2-hydroxyethyl methacrylate (p(HEMA)) hydrogel could avoid peritoneal adhesion in female dogs. METHODS: Eight animals (group PP) had a polypropylene mesh implanted to correct a defect in the rectal abdominal muscle, whereas in the other group (group PH) the polypropylene mesh was coated with p(HEMA) composite on the surface facing the peritoneal area. RESULTS: Adhesions were observed on the mesh in 62.5 percent of the PP group. In the PH group adhesions were present only on the suture lines. CONCLUSION: p(HEMA) hydrogel was well tolerated and effective in avoiding visceral and omental adhesions on the surface of the polypropylene mesh.

OBJETIVO: Avaliar se o revestimento da face visceral de uma tela de polipropileno com 2-hidroxietil dimetacrilato (p(HEMA)) poderia evitar aderências peritoniais em cadelas. MÉTODOS: Em oito animais (Grupo PP) foram implantadas telas de polipropileno para correção de um defeito do músculo reto abdominal, enquanto em outro grupo (Grupo PH) fez-se a implantação de uma tela de polipropileno cuja face peritonial foi revestida por 2-hidroxietil dimetacrilato (p(HEMA)). RESULTADOS: Foram observados 62,5 por cento de aderências peritoniais sobre a tela nos animais do Grupo PP, enquanto que no Grupo PH estas não ocorreram, exceto sobre a linha se sutura. CONCLUSÃO: O hidrogel de p(HEMA) foi bem tolerado pelos animais e mostrou-se efetivo na prevenção das aderências viscerais e omentais sobre a tela de polipropileno.

Coceptos básicos en el manejo de las heridas / Basic concepts on wound management

Los criterios y medidas utilizados en el manejo de las heridas y su fundamento actual constituyen el elemento central de esta nota. Aunque muchos aspectos técnicos, de uso diario en la práctica medicoquirúrgica, se mantienen plenamente vigentes, existen otros,como las características del medio interno local, laimportancia del tejido de granulación y el rol de laantisepsia y la cobertura cutánea, que han sufrido cambios significativos y requieren ser actualizados

Biomechanical and histological evaluation of hydrogel implants in articular cartilage

We evaluated the mechanical behavior of the repaired surfaces of defective articular cartilage in the intercondylar region of the rat femur after a hydrogel graft implant. The results were compared to those for the adjacent normal articular cartilage and for control surfaces where the defects remained empty. Hydrogel synthesized by blending poly(2-hydroxyethyl methacrylate) and poly(methyl methacrylate-co-acrylic acid) was implanted in male Wistar rats. The animals were divided into five groups with postoperative follow-up periods of 3, 5, 8, 12 and 16 weeks. Indentation tests were performed on the neoformed surfaces in the knee joint (with or without a hydrogel implant) and on adjacent articular cartilage in order to assess the mechanical properties of the newly formed surface. Kruskal-Wallis analysis indicated that the mechanical behavior of the neoformed surfaces was significantly different from that of normal cartilage. Histological analysis of the repaired defects showed that the hydrogel implant filled the defect with no signs of inflammation as it was well anchored to the surrounding tissues, resulting in a newly formed articular surface. In the case of empty control defects, osseous tissue grew inside the defects and fibrous tissue formed on the articular surface of the defects. The repaired surface of the hydrogel implant was more compliant than normal articular cartilage throughout the 16 weeks following the operation, whereas the fibrous tissue that formed postoperatively over the empty defect was stiffer than normal articular cartilage after 5 weeks. This stiffness started to decrease 16 weeks after the operation, probably due to tissue degeneration. Thus, from the biomechanical and histological point of view, the hydrogel implant improved the articular surface repair.

Growth modulation of fibroblasts by chitosan-polyvinyl pyrrolidone hydrogel: implications for wound management?

Wounds in adults and fetuses differ in their healing ability with respect to scar formation. In adults, wounds lacking the epidermis exhibit excess collagen production and scar formation. Fibroblasts synthesize and deposit a collagen rich extracellular matrix. The early migration and proliferation of fibroblasts in the wound area is implicated in wound scarring. We have synthesized a hydrogel from chitosan-polyvinyl pyrrolidone (PVP) and examined its effect on fibroblast growth modulation in vitro. The hydrogel was found to be hydrophilic as seen from its octane contact angle (141.2+/-0.37 degrees). The hydrogel was non-toxic and biocompatible with fibroblasts and epithelial cells as confirmed by the 3(4,5-dimethylthiazolyl-2)-2, 5-diphenyl tetrazolium bromide (MTT) as-say. It showed dual properties by supporting growth of epithelial cells (SiHa) and selectively inhibiting fibro-blast (NIH3T3) growth. Growth inhibition of fibroblasts resulted from their inability to attach on to the hydrogel. These findings are supported by image analysis, which revealed a significant difference (P<0.05) between the number of fibroblasts attached to the hydrogel in tissue culture as compared to tissue culture treated polystyrene (TCPS) controls. However, no significant difference was observed (P>0.05) in the number of epithelial (SiHa) cells attached on to the hydrogel as compared to the TCPS control. Although in vivo experiments are awaited, these findings point to the possible use of chitosan-PVP hydrogels in wound-management.

Avaliação de curativos hidroativos e hidrogels na epitalização de feridas em ratas / Evaluation of dressing hydrocolloid and epithelization of rat wounds

Um meio tópico é uma substância que é aplicada em uma ferida, sendo o curativo uma cobertura que visa proteger e provocar a cicatrização. O objetivo do presente estudo foi avaliar dois tipos de curativos em rata.Utilizou-se dois Grupos formados de 5 ratas cada (Rattus norvegicus, albinus Wistar) que foram submetidos a ressecção cirúrgica com "punch" 0,6mm diâmetro em região dorsal e realizados curativos de hidrocolóide no grupo I e hidrogels no grupo II até a epitelização final. Os dois curativos apresentaram a mesma eficácia na epitalização de feridas em ratas