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Advances in Biodegradable Nano-Sized Polymer-Based Ocular Drug Delivery.

ABSTRACT: The effective delivery of drugs to the eye remains a challenge. The eye has a myriad of defense systems and physiological barriers that leaves ocular drug delivery systems with low bioavailability profiles. This is mainly due to poor permeability through the epithelia and rapid clearance from the eye following administration. However, recent advances in both polymeric drug delivery and biomedical nanotechnology have allowed for improvements to be made in the treatment of ocular conditions. The employment of biodegradable polymers in ocular formulations has led to improved retention time, greater bioavailability and controlled release through mucoadhesion to the epithelia in the eye, amongst other beneficial properties. Nanotechnology has been largely investigated for uses in the medical field, ranging from diagnosis of disease to treatment. The nanoscale of these developing drug delivery systems has helped to improve the penetration of drugs through the various ocular barriers, thus improving bioavailability. This review will highlight the physiological barriers encountered in the eye, current conventional treatment methods as well as how polymeric drug delivery and nanotechnology can be employed to optimize drug penetration to both the anterior and posterior segment of the eye.

SUBMITTER: Lynch C

PROVIDER: S-EPMC6722735 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Advances in Biodegradable Nano-Sized Polymer-Based Ocular Drug Delivery.

Lynch Courtney C Kondiah Pierre P D PPD Choonara Yahya E YE du Toit Lisa C LC Ally Naseer N Pillay Viness V

Polymers 20190820 8

The effective delivery of drugs to the eye remains a challenge. The eye has a myriad of defense systems and physiological barriers that leaves ocular drug delivery systems with low bioavailability profiles. This is mainly due to poor permeability through the epithelia and rapid clearance from the eye following administration. However, recent advances in both polymeric drug delivery and biomedical nanotechnology have allowed for improvements to be made in the treatment of ocular conditions. The e ...[more]

PMID: 31434273

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Project description:A fully biodegradable zwitterionic polymer and the corresponding conjugate with paclitaxel (PTX) were synthesized as promising biomaterials. Allyl-functionalized polylactide (PLA) was employed as the precursor of polymer backbones. UV-induced thiol-ene reaction was conducted to conjugate thiol-functionalized sulfobetaine (SB) with the PLA-based backbone. The resulting zwitterionic polymer did not exhibit considerable cytotoxicity. A polymer-drug conjugate was also obtained by thiol-ene reaction of both thiol-functionalized SB and PTX with allyl-functionalized PLA. The conjugate could readily form narrowly-dispersed nanoparticles in aqueous solutions with a volume-average hydrodynamic diameter (Dh,V) of 19.3 ± 0.2 nm. Such a polymer-drug conjugate-based drug delivery system showed full degradability, well-suppressed non-specific interaction with biomolecules, and sustained drug release. In vitro assessments also confirmed the significant anti-cancer efficacy of the conjugate. After 72 h incubation with PLA-SB/PTX containing 10 µg/mL of PTX, the cell viabilities of A549, MCF7, and PaCa-2 cells were as low as 20.0 ± 2.5%, 1.7 ± 1.7%, and 14.8 ± 0.9%, respectively. Both flow cytometry and confocal microscopy suggested that the conjugates could be easily uptaken by A549 cells before the major release of PTX moieties. Overall, this work elucidates promising potentials of biodegradable zwitterionic polymer-based materials in biomedical applications.Statement of significanceThe applicability of FDA-approved biodegradable aliphatic polyesters has been significantly restricted because they are hydrophobic and lack functionalities. Recently zwitterionic polymers have emerged as promising hydrophilic biomaterials, but most of the reported zwitterionic polymers are non-biodegradable. This study reports a novel aliphatic polyester-based zwitterionic polymer and the corresponding polymer-drug conjugate. Their aliphatic polyester and zwitterionic components provide them with high enzymatic degradability and low nonspecific interactions with biomolecules, respectively. While the zwitterionic polymer did not show noticeable cytotoxicity, the corresponding polymer-anticancer drug conjugate exhibited acid-sensitive sustained drug release, remarkable effectiveness in killing cancer cells, as well as the ready cellular internalization. This work lays a foundation for the further development of synthetic biodegradable zwitterionic polymer-based materials which potentially may have broad and significant biomedical applications.

Dataset Information

Advances in Biodegradable Nano-Sized Polymer-Based Ocular Drug Delivery.

Publications

Advances in Biodegradable Nano-Sized Polymer-Based Ocular Drug Delivery.

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