Abstract
Dissolving microneedles (dMNs) are proving to be attractive minimally invasive ophthalmic delivery systems owing to their superior ability to deliver a variety of therapeutic agents through the cornea or sclera. Nevertheless, dMN formulation is most often complicated when poorly water-soluble drugs are used, because dMNs usually contain water-soluble polymers that dissolve quickly in ocular tissues. Here, we synthesized the thermosensitive in-situ micelle-forming poly (N-isopropyl acrylamide)-b-poly (l-glutamic acid) (PNIPAAm-b-PGA) copolymer which was soluble in organic and aqueous solvents, making it possible to prepare MNs containing hydrophilic drugs. After full characterization of the copolymer, it was successfully used to fabricate dMNs using the micro-molding technique. Remarkably, they generated in-situ nanomicelles (NMCs) with sizes below 100 nm allowing for efficient dexamethasone (DEX) encapsulation. In this regard, the concentration of PNIPAAm-b-PGA copolymer was optimized to produce microneedles with acceptable properties. A series of characteristics were assessed for microneedles, including mechanical and insertion properties, drug loading, in vitro release behavior, and in vitro permeation. Overall, the findings indicated that poly PNIPAAm-b-PGA copolymer is capable of self-assembling into NMCs and can significantly incorporate DEX as a hydrophobic drug, improving the trans-scleral DEX ) permeation across the sclera, making it a promising system for treating posterior ocular diseases.
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