NIR photothermal-activable drug-conjugated microcapsules for in vitro targeted delivery and release: An alternative treatment of diabetic retinopathy

Diabetic retinopathy (DR) is one of the most serious complications of diabetes, which leads to blindness. By addressing the traditional treatment limitations, we developed a novel light-responsive targeted polymeric microcapsule able to encapsulate a near infrared (NIR) photoactive fluorophore - Indocyanine Green, owing to its photothermal properties. Moreover, for an efficient in vitro targeted drug delivery, the fluorescent microsystem was conjugated with a therapeutic agent, i.e., Avastin drug - a Food and Drug Administration approved therapeutic antibody. The microcapsules were fabricated and evaluated in terms of morphology, encapsulation and drug conjugation efficiency and its release capacity. Avastin-conjugated microcapsules with an average dimension of 4.5 +/- 0.35 mu m were obtained, according to Scanning Electron Microscopy and Re-Scanning Confocal Microscopy (RCM) investigations. The capacity of the microcapsules to operate as effective phototherapeutic agents by generating heat under NIR laser irradiation was evaluated, followed by the investigation of the microcapsule's shell rupture and NIR laser-induced release of Avastin. The biocompatibility of the Avastinconjugated microcapsules was proven by WST-1 assay. In vitro cellular internalization and localization of the Avastin microcarriers were determined through Conventional fluorescence microscopy, RCM and Transmission Electron Microscopy imaging techniques. Finally, the Avastin-conjugated microcapsules were validated for in vitro targeted drug delivery and release directly under simulated DR conditions, which could certainly become a successful strategy in DR fighting.

Automated summary

Diabetic retinopathy (DR) is a serious complication of diabetes that can cause blindness. In this study, a light-responsive targeted polymeric microcapsule was developed to encapsulate a near infrared (NIR) photoactive fluorophore - Indocyanine Green, and conjugated with Avastin to form an efficient in vitro targeted drug delivery system. The microcapsules showed biocompatibility and the ability to generate heat under NIR laser irradiation, leading to the release of Avastin. The Avastin-conjugated microcapsules were validated for in vitro targeted drug delivery and release under simulated DR conditions.