CONTACT LENSES ARE one of the most frequently prescribed medical devices, and there has been a significant interest in their use for drug delivery for ocular diseases. The challenge has been in controlling or modulating the release of drugs from contact lenses or contact lens materials. In most cases, without modification, drugs undergo a large burst release after they are loaded into lenses, leaving smaller amounts of them to be delivered as time goes on (Pereira-da-Mota et al, 2022). Therefore, development of methods that can lead to sustained release of ocular drugs have been a focus in tailoring ocular drug delivery from these devices (Tieppo et al, 2014).

Examining the utility of incorporating biodegradable polymers for this application can be useful because they can be hydrolyzed to form biocompatible degradation products, eliminating the need for surgical or other interventions for their removal, but they have not yet been trialed extensively in contact lenses.

Typically, biodegradable polymers have backbones consisting of different functional groups, including ester, amide, and ether bonds, which govern their properties and degradation mechanisms, and drug release is tied to the degradation rate (Wang et al, 2020). Several biodegradable polymeric ocular drug delivery systems have reached clinical trials or have been released to the market, including a brimonidine intravitreal implant and ranibizumab-loaded microspheres (Kuno and Fujii, 2012).

Commercially released devices interestingly illustrate the advantages of full degradable polymers. One releases fluocinolone acetonide to manage posterior segment inflammation and includes nonbiodegradable portions that must be surgically removed after the biodegradable portion is exhausted. In contrast, another releases dexamethasone to the posterior segment and is composed of purely biodegradable polymers whose degradation products are eliminated from the eye over time (Subrizi et al, 2019).

MECHANISMS OF RELEASE

The drug is released from a matrix system when the system degrades upon interaction with the surrounding environment. The degradation process can be physical (abrasion, fracture, disintegration), chemical (dissolution, ionization, protonation), or biological (pH, enzyme, immune response).

Generally, for polymeric systems, degradation occurs by cleavage of the polymer backbone and cross-links; however, when used in the body, degradation, dissolution, and diffusion likely are all occurring simultaneously to varying degrees (Wang et al, 2020). For example, chitosan is a widely used biodegradable polymer. Enzymes such as lysozyme in the tear film can degrade chitosan by hydrolyzing linkages between glucosamine–N-acetyl-glucosamine, N-acetyl-glucosamine–N-acetyl-glucosamine, and glucosamine–glucosamine groups (Lončarević et al, 2017).

Gelatin, another biodegradable polymer, is more likely degraded by the matrix metallopeptidases present in the eye (Cui et al, 2017). Given the changes in matrix metalloproteinase levels and activity during different disease states, this could allow tailored gelatin degradation by the ocular surface in response to the eye (Heltmann-Meyer, 2021).

One example of a degradable implant is a long-acting intracameral implant for non-pulsatile and steady release of the prostaglandin agonist bimatoprost to treat high intraocular pressure (IOP). The matrix used in this product consists of polyD, L-lactide, poly(ethylene glycol) 3550, and poly(lactic-co-glycolic acid), which eventually degrades to lactic and glycolic acids. The IOP-lowering efficacy of this implant allows for the drug to be released steadily over four to six months. This method delivers the drug close to the target tissues at higher concentrations compared to eye drops (Sirinek and Lin, 2022; O’Brien Laramy and Nagapudi, 2022).

INCORPORATION WITH CLs

Future studies could rely on formulating a material that has a controlled degradation rate, tailored to the disease being treated. More information will follow about opportunities and challenges of doing this specifically in a contact lens. CLS

References

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9. Sirinek PE, Lin MM. Intracameral sustained release bimatoprost implants (Durysta). Semin Ophthalmol. 2022 Apr 3;37:385-390.
10. O’Brien Laramy MN, Nagapudi K. Long-acting ocular drug delivery technologies with clinical precedent. Expert Opin Drug Deliv. 2022 Oct;19:1285-1301.