PLA Stereocomplexed Microspheres Modified with Methyl-β-Cyclodextrin as an Atropine Delivery System. Synthesis and Characterization

Abstract

The delivery of atropine (AT) in the conventional form often exerts systematic side effects, including fever, convulsion or even death. Therefore, the novel microparticles drug delivery systems could be ideal to minimize the dose and toxicity of AT. For this purpose, we propose the use of stereocomplexed spherical microspheres with a diameter of 2 μm loaded with AT to be administered through the ocular route. The spontaneous precipitation was employed to prepare microspheres from poly-l-lactide (PLLA) and poly-d-lactide (PDLA) with methyl-β-cyclodextrin (MnβCD) or dipentaerythritol (DPE) core which can host the hydrophobic drugs in its interior. We could demonstrate that for a model system composed of MnβCD the inclusion of AT in CD cavity can be achieved. Although the morphology and size of microspheres composed of PLAs with MnβCD and DPE do not differ significantly, the release of the AT was slower for the PLAs with MnβCD core. This means that by alteration of the microsphere building blocks: PLAs with MnβCD versus DPE core, we could modulate the drug release. Our findings not only provide a novel strategy to prepare Sc-PLA microcarriers with the controllable release of the cycloplegic agent but also offer the application of Sc-PLA microspheres in anti-myopia therapy, due to their suitable size for ocular administration.