RESUMO
INTRODUCTION: The most common treatment for Primary Open-Angle Glaucoma (POAG) is the daily use of eye drops. Sustained-release drug delivery systems have been developed to improve patient adherence by achieving prolonged therapeutic drug concentrations in ocular target tissues while limiting systemic exposure. The purpose of this study is to compare the efficacy and safety of bimatoprost inserts with bimatoprost eye drops in patients with POAG and Ocular Hypertension (OH). METHODS: We include OH and POAG patients aged between 40 and 75 years-old. Both OH and POAG patients had intraocular pressure (IOP) greater than 21 and ≤30 mmHg at 9:00 am without glaucoma medication and normal biomicroscopy. Five normal patients with IOP≤14 mmHg constitute the control group. A chitosan-based insert of bimatoprost was placed at the upper conjunctival fornix of the right eye. In the left eye, patients used one drop of LumiganTM daily at 10:00 pm. For statistical analysis, a two-way analysis of variance (ANOVA), Student t-test, and paired t-test is used. RESULTS: Sixteen POAG and 13 OH patients with a mean age of 61 years were assessed. In both eyes, IOP reduction was similar during three weeks of follow-up (19.5±2.2 mmHg and 16.9±3.1 mmHg), insert, and eye drop, respectively; P=0.165). The percentage of IOP reduction in the third week was 30% for insert and 35% for eye drops (P=0.165). No intolerance or discomfort with the insert was reported. Among the research participants, 58% preferred the use of the insert while 25% preferred eye drops, and 17% reported no preference. CONCLUSION: Bimatoprost-loaded inserts showed similar efficacy to daily bimatoprost eye drops during three weeks of follow up, without major side effects. This might suggest a possible change in the daily therapeutic regimen for the treatment of POAG and OH.
Assuntos
Glaucoma de Ângulo Aberto , Glaucoma , Hipertensão Ocular , Adulto , Idoso , Amidas , Anti-Hipertensivos , Bimatoprost , Glaucoma de Ângulo Aberto/tratamento farmacológico , Humanos , Pressão Intraocular , Pessoa de Meia-Idade , Hipertensão Ocular/tratamento farmacológico , Soluções OftálmicasRESUMO
The aim of this study was to develop and evaluate the effects of chitosan inserts for sustained release of the angiotensin-converting enzyme 2 (ACE2) activator, diminazene aceturate (DIZE), in experimental glaucoma. Monolayer DIZE loaded inserts (D+I) were prepared and characterized through swelling, attenuated total reflectance Fourier transformed infrared spectroscopy (ATR-FTIR), differential scanning calorimetry (DSC) and in vitro drug release. Functionally, the effects of D+I were tested in glaucomatous rats. Glaucoma was induced by weekly injections of hyaluronic acid (HA) into the anterior chamber and intraocular pressure (IOP) measurements were performed. Retinal ganglion cells (RGC) and optic nerve head cupping were evaluated in histological sections. Biodistribution of the drug was accessed by scintigraphic images and ex vivo radiation counting. We found that DIZE increased the swelling index of the inserts. Also, it was molecularly dispersed and interspersed in the polymeric matrix as a freebase. DIZE did not lose its chemical integrity and activity when loaded in the inserts. The functional evaluation demonstrated that D+I decreased the IOP and maintained the IOP lowered for up to one month (last week: 11.0 ± 0.7 mmHg). This effect of D+I prevented the loss of RGC and degeneration of the optic nerve. No toxic effects in the eyes related to application of the inserts were observed. Moreover, biodistribution studies showed that D+I prolonged the retention of DIZE in the corneal site. We concluded that D+I provided sustained DIZE delivery in vivo, thereby evidencing the potential application of polymeric-based DIZE inserts for glaucoma management.
Assuntos
Diminazena/análogos & derivados , Proteínas do Olho/agonistas , Glaucoma/tratamento farmacológico , Peptidil Dipeptidase A/efeitos dos fármacos , Administração Oftálmica , Enzima de Conversão de Angiotensina 2 , Animais , Pressão Sanguínea/efeitos dos fármacos , Varredura Diferencial de Calorimetria , Quitosana , Preparações de Ação Retardada , Diminazena/administração & dosagem , Diminazena/farmacocinética , Avaliação Pré-Clínica de Medicamentos , Ativação Enzimática/efeitos dos fármacos , Glaucoma/induzido quimicamente , Glaucoma/patologia , Ácido Hialurônico/toxicidade , Pressão Intraocular/efeitos dos fármacos , Masculino , Microscopia Eletrônica de Varredura , Ratos , Ratos Wistar , Espectroscopia de Infravermelho com Transformada de Fourier , Distribuição TecidualRESUMO
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.