Bimatoprost-loaded ocular inserts as sustained release drug delivery systems for glaucoma treatment: in vitro and in vivo evaluation.

The purpose of the present study was to develop and assess a novel sustained-release drug delivery system of Bimatoprost (BIM). Chitosan polymeric inserts were prepared using the solvent casting method and characterized by swelling studies, infrared spectroscopy, differential scanning calorimetry, drug content, scanning electron microscopy and in vitro drug release. Biodistribution of 99mTc-BIM eye drops and 99mTc-BIM-loaded inserts, after ocular administration in Wistar rats, was accessed by ex vivo radiation counting. The inserts were evaluated for their therapeutic efficacy in glaucomatous Wistar rats. Glaucoma was induced by weekly intracameral injection of hyaluronic acid. BIM-loaded inserts (equivalent to 9.0 µg BIM) were administered once into conjunctival sac, after ocular hypertension confirmation. BIM eye drop was topically instilled in a second group of glaucomatous rats for 15 days days, while placebo inserts were administered once in a third group. An untreated glaucomatous group was used as control. Intraocular pressure (IOP) was monitored for four consecutive weeks after treatment began. At the end of the experiment, retinal ganglion cells and optic nerve head cupping were evaluated in the histological eye sections. Characterization results revealed that the drug physically interacted, but did not chemically react with the polymeric matrix. Inserts sustainedly released BIM in vitro during 8 hours. Biodistribution studies showed that the amount of 99mTc-BIM that remained in the eye was significantly lower after eye drop instillation than after chitosan insert implantation. BIM-loaded inserts lowered IOP for 4 weeks, after one application, while IOP values remained significantly high for the placebo and untreated groups. Eye drops were only effective during the daily treatment period. IOP results were reflected in RGC counting and optic nerve head cupping damage. BIM-loaded inserts provided sustained release of BIM and seem to be a promising system for glaucoma management.

Adenocarcinoma de células glassy de colo de útero em paciente jovem com HPV: relato de caso / Glassy cells adenocarcinoma of the uterine cervix in young patient with HPV: case report

Introdução: o câncer de colo uterino é a segunda neoplasia mais comum em mulheres no mundo e a terceira entre a população feminina brasileira. O HPV desempenha um importante papel no desenvolvimento de neoplasias cervicais, estando presente em 95% dos casos de câncer de colo de útero. O carcinoma de células glassy é um carcinoma adenoescamoso misto pouco diferenciado, raro, de comportamento agressivo e altamente resistente à radioterapia. Atinge tipicamente mulheres jovens, com pico de incidência entre a 3a e a 4a década de vida. Está associado aos tipos 16 e 18 de HPV e sua evolução é aceleradana gravidez. O tempo médio de sobrevida após o diagnóstico é de 10 meses. Relato de caso: mulher, 26 anos, multípara, com história prévia de condiloma acuminado, apresentou lesões genitais que agravaram em sua última gestação, tendo evoluído com massas exofíticas diagnosticadas como carcinoma de células glassy, com curso agressivo e metástases precoces, não responsivo à radioterapia e progressão ao óbito em 16 meses. Conclusão: o carcinoma de células glassy destaca-se pela agressividade e rapidez de seu desenvolvimento, levando ao óbito mulheres jovens, em idade fértil e produtiva. Diante da sua baixa resposta às terapias antineoplásicas, destaca-se a importância de sua prevenção, seu diagnóstico e tratamento precoces, possíveis mediante o usode preservativos, da vacina contra o HPV e do exame colpocitológico regular, com coleta de material endocervical e acompanhamento eficaz.

Introduction: cervical cancer is the second most common cancer in women worldwide and the third among the female population in Brazil. HPV plays an important role in the development of cervical cancer, being present in 95% of cases of cancer of the cervix. Glassy cells carcinoma is a poorly differentiated mixed adenosquamous carcinoma, rare, aggressive and highly resistant to radiotherapy. It typically affects young women, with peak incidence between the third and fourth decades of life. It is associated with types 16 and 18 of HPV and its evolution is acelerated during pregnancy. The average survival time after diagnosis is 10 months.Case Report: woman, 26 years old, multiparous, with a history of condyloma acuminata, genital lesions that had increased in their last pregnancy, having evolved with exophytic masses diagnosed as glassy cell carcinoma, and aggressive course with early metastases not responsive to radiation therapy and progression to death in 16 months. Conclusion: glassy cells carcinoma is distinguished by aggressiveness and speed of its development, leading child-bearing age and productive young women to death. In view of its low response to anticancer therapies, we highlight the importance of its prevention, early diagnosis and treatment, possible through the use of condoms, the vaccine against HPV and cervical cytology at regular collection of endocervical material and effective monitoring.