NANOPARTICLES BASED ON PHA OF MICROBIOLOGICAL ORIGIN FOR THE OCULAR DELIVERY OF PRANOPROFEN

Topical NSAIDs are widely used for the treatment of eye pain and inflammation conditions, including post-surgical assistance. For example, patients undergoing cataract surgery who have been pretreated with topical NSAIDs have a larger pupil size during surgery. This allows for safer and more efficient medical procedures and reduces postoperative pain and inflammation. This work belongs to the wider HIPPOCRATES PON project, aimed at identifying valid and scalable nanotechnological platforms for an effective and targeted drug delivery in various ophthalmic diseases, with the side aim to minimize drug dosage, toxicity, and frequency of administration. The goal of this particular work was the production of nanoparticles made of poly(hydroxyalkanoates) (PHAs) produced by microbiological methods [1, 2], loaded with the NSAI agent pranoprofen (PPF). This drug is under active investigation for ocular therapies, and has been also tested in nanoscaled delivery systems [3]. PHAs are macromolecules synthesized by many types of Gram (+) and Gram (-) bacteria that, under appropriate culture conditions, accumulate high concentrations of these compounds as granules for energy and nutrient reserve. PHA composition depends on the bacterial strain used, but also from the culture medium in which the bacteria grow. Our nanoparticle systems were prepared by a solvent displacement method, obtaining carriers with a mean size compatible with the ocular application (160-200 nm; PDI ˂ 0.3) and a net negative Zeta potential (-17 mV). They showed high encapsulation efficiency values for PPF and were able to release the incorporated drug with a constant evolution up to 12 h. Interestingly, these carriers can be easily sterilized through sterile filtration; to this aim, different 0.22 µm filtering materials have been identified on the market and tested to guarantee high yields of sterilizing filtration. In vitro MTT assay on rabbit corneal SIRC cells showed that PPF-loaded PHA nanoparticles are highly tolerated, except for the formulations added of one of the tested cryoprotectants (HP-β-CD) and containing high drug concentrations.