Journal
NANOSCALE
Volume 9, Issue 32, Pages 11754-11764Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c7nr03221h
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Funding
- Ministry of Science and Technology of Taiwan [MOST104-2314-B-182-008-MY3, MOST 105-2811-B-182-002, MOST 105-2811-B-182-008]
- Chang Gung Memorial Hospital [CMRPD2C0071-73]
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Glaucoma is an eye-related disease accompanied by highly elevated intraocular pressure (IOP), which causes damage to the optic nerve and results in vision loss and even blindness. Although the treatment of glaucoma with eye drops may reduce the IOP, eye drops have some limitations, such as poor patient compliance and short duration. To develop drug carriers that facilitate the sustained and long-term release of drugs for glaucoma therapy, we synthesized poly(e-caprolactone) nanoparticles (PCL NPs) capable of loading pilocarpine, a widely used drug for the treatment of dry eye and glaucoma. We prepared two types of PCL NPs, namely, nanospheres (NSs), which are solid spheres capable of harboring the drug in their solid mass, and nanocapsules (NCs), which are hollow spherical structures for encapsulating the drug. The influence of the vesicular structure of PCL NPs on the drug loading efficiencies and release was investigated. The loading of pilocarpine in the PCL NCs was approximately 3 times higher than that in the PCL NSs. In addition, pilocarpine-loaded PCL NCs (PILO-PCL NCs) exhibited a sustained drug release profile. Effective pharmacological responses (i.e., IOP reduction and pupillary constriction) were observed in rabbits intracamerally treated with pilocarpine-loaded PCL NPs. Moreover, the PILO-PCL NCs show long-term therapeutic ability in alleviating ocular hypertension-induced corneal and retinal injuries under physiological conditions, even after 42 days. The results of in vivo studies also reveal that the PCL NCs are advantageous for the treatment of chronic ocular hypertension in glaucomatous eyes.
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