Natural biomaterials for contact lens-based ophthalmic drug delivery systems.

Polymeric drug delivery technology, which allows for medicinal ingredients to enter a cell more easily, has advanced considerably in recent decades. Innovative medication delivery strategies use biodegradable and bio-reducible polymers, and progress in the field has been accelerated by future possible research applications. Natural polymers utilized in polymeric drug delivery systems include arginine, chitosan, dextrin, polysaccharides, poly(glycolic acid), poly(lactic acid), and hyaluronic acid. Additionally, poly(2-hydroxyethyl methacrylate), poly(N-isopropyl acrylamide), poly(ethylenimine), dendritic polymers, biodegradable polymers, and bioabsorbable polymers as well as biomimetic and bio-related polymeric systems and drug-free macromolecular therapies have been employed in polymeric drug delivery. Different synthetic and natural biomaterials are in the clinical phase to mitigate different diseases. Drug delivery methods using natural and synthetic polymers are becoming increasingly common in the pharmaceutical industry, with biocompatible and bio-related copolymers and dendrimers having helped cure cancer as drug delivery systems. This review discusses all the above components and how, by combining synthetic and biological approaches, micro- and nano-drug delivery systems can result in revolutionary polymeric drug and gene delivery devices.

In recent years, wearable contact lenses for medical applications have attracted significant attention, as they enable continuous real-time recording of physiological information via active and noninvasive measurements. These devices play a vital role in continuous monitoring of intraocular pressure (IOP), noninvasive glucose monitoring in diabetes patients, drug delivery for the treatment of ocular illnesses, and colorblindness treatment. In specific, this class of medical devices is rapidly advancing in the area of drug loading and ocular drug release through incorporation of electrospun fibers. The electrospun fiber matrices offer a high surface area, controlled morphology, wettability, biocompatibility, and tunable porosity, which are highly desirable for controlled drug release. This article provides an overview of the advances of contact lens devices in medical applications with a focus on four main applications of these soft wearable devices: (i) IOP measurement and monitoring, (ii) glucose detection, (iii) ocular drug delivery, and (iv) colorblindness treatment. For each category and application, significant challenges and shortcomings of the current devices are thoroughly discussed, and new areas of opportunity are suggested. We also emphasize the role of electrospun fibers, their fabrication methods along with their characteristics, and the integration of diverse fiber types within the structure of the wearable contact lenses for efficient drug loading, in addition to controlled and sustained drug release. This review article also presents relevant statistics on the evolution of medical contact lenses over the last two decades, their strengths, and the future avenues for making the essential transition from clinical trials to real-world applications.

Comparative study of nanosized cross-linked sodium-, linear sodium- and zinc-hyaluronate as potential ocular mucoadhesive drug delivery systems

Ocular drug delivery through hydrogel contact lenses has great potential for the treatment of ocular diseases. Previous studies showed that the loading of lipophilic vitamin E to silicone-hydrogel contact lenses was beneficial in ocular drug delivery. We hypothesized that vitamin E loading to another type of popular hydrogel contact lenses, pHEMA-hydrogel contact lenses, improves ocular drug delivery by increasing the drug loading or the duration of drug release. Loading of vitamin E to pHEMA-hydrogel contact lenses significantly increased the loading of a hydrophilic drug surrogate (Alexa Fluor 488 dye) and two hydrophilic glaucoma drugs (timolol and brimonidine) to the lenses by 37.5%, 19.1%, and 18.7%, respectively. However, the release duration time was not significantly altered. Next, we hypothesized that the lipophilic nature of vitamin E attributes to the enhanced drug loading. Therefore, we investigated the effects of co-loading of another lipophilic vitamin, vitamin A, on drug surrogate delivery. We found out that vitamin A loading also increased the loading of the drug surrogate to pHEMA-hydrogel contact lenses by 30.3%. Similar to vitamin E loading, vitamin A loading did not significantly alter the release duration time of the drug or drug surrogate.

Challenges and strategies for ocular posterior diseases therapy via non-invasive advanced drug delivery

Currently, bacterial conjunctivitis is managed by multiple antibiotic eye-drop solution, which is highly inefficient due to low ocular bioavailability and frequent dosing. Therapeutic soft contact lenses can be used to sustain the release of ocular drugs. However, the conventional soaking method (economic and widely used) showed low drug uptake and high burst release, and the optophysical properties of the contact lens were altered for clinical application. In this paper, novel ofloxacin-loaded niosomes were developed to increase the drug loading capacity of contact lenses while also sustaining ocular drug delivery. Ofloxacin-loaded niosomes were prepared by the thin film hydration technique with three levels of cholesterol. The niosome-laden contact lenses (OFL-Nio-L) led to improved optophysical properties (swelling, transmittance, oxygen permeability) and lysozyme adherence compared to the conventional soaked contact lens (CV-OFL-L). The in vitro drug release data of CV-OFL-L showed high burst release, while OFL-Nio-L lenses showed sustained release up to 48-96h. In a rabbit tear fluid model, the OFL-Nio-100-L lens showed a high drug concentration at all-time points compared to the CV-OFL-L and eye-drop solution. The efficacy study in the rabbit model showed improved healing effect with OFL-Nio-100-L lens compared to frequent eye-drop therapy. In conclusion, the paper demonstrated the successful application of niosomes to deliver ofloxacin using contact lens without affecting the critical lens properties to substitute eye-drop therapy.

Ocular drug delivery poses a significant challenge due to the intricate structure and protective barriers present in the eye. Traditional techniques, including systemic administration and topical eye drops, often have limited therapeutic efficacy and poor bioavailability. However, the emergence of mucoadhesive ocular nanoparticles has the potential to revolutionize ocular drug delivery by overcoming these challenges. Eye drops remain a popular non-invasive method of treating ocular ailments. Nevertheless, conventional eye drop formulations are associated with several limitations, such as rapid drainage from the eye, low bioavailability, and frequent administrations. Mucoadhesive nanoparticles present a promising solution to address these issues by enhancing drug retention and permeation in the eye. This chapter offers a comprehensive overview of recent developments in mucoadhesive ocular nanoparticles and their implications for ocular drug delivery. It discusses the anatomy and protective barriers of the eye that influence drug penetration and the need for innovative drug delivery systems. The chapter explores various natural and synthetic mucoadhesive polymers used in nanoparticle formulations and their interactions with ocular tissues. Additionally, it highlights the development and characterization of nanosystems, including micelles, liposomes, nanosuspensions, and nanogels, that incorporate mucoadhesive properties to enhance ocular drug delivery. The potential applications of mucoadhesive ocular nanoparticles in addressing ocular diseases affecting both the anterior and posterior segments are discussed. Furthermore, the chapter emphasizes the importance of understanding the anatomical and physiological challenges in ocular drug delivery to design effective and safe drug delivery systems. Overall, this book chapter serves as a valuable resource for researchers, scientists, and pharmaceutical experts working in the field of ocular drug delivery. It provides insights into the recent advancements in mucoadhesive ocular nanoparticles and their potential implications in improving therapeutic outcomes and patient compliance for various ocular disorders.

Timolol-eluting graphene oxide laden silicone contact lens: Control release profile with improved critical lens properties

Advances in drug-loaded contact lenses for glaucoma: Materials, evaluation parameters, and novel drug delivery strategies with modified nanoparticles

Enhanced drug loading efficiency of contact lenses via salt-induced modulation

Ocular drug delivery presents a persistent clinical challenge due to the protective anatomical structure of the eye, physiological barriers such as reflex blinking, and continuous tear fluid turnover. These factors significantly limit the bioavailability of topically applied medications, reducing the therapeutic effectiveness of conventional formulations, such as eye drops, ointments, and suspensions, particularly in the management of chronic ocular disorders, including dry eye syndrome, diabetic retinopathy, and age-related macular degeneration. Drug-eluting contact lenses (DECLs) offer a promising alternative, enabling sustained, localized, and controlled drug release directly at the ocular surface. While several reviews have addressed contact lenses as drug delivery platforms, this work provides a distinct perspective by focusing specifically on biodegradable polymer-based systems. Emphasis is placed on recent advances in the design and fabrication of DECLs using natural and synthetic biodegradable polymers, which offer superior biocompatibility, customizable degradation kinetics, and the capacity for programmable drug release. This review discusses the selection criteria for polymer matrices, strategies for drug incorporation, and key factors influencing release profiles. Moreover, this study highlights innovative methodologies and therapeutic approaches that differentiate it from the existing literature, providing a timely and comprehensive resource for researchers developing next-generation polymeric ocular drug delivery systems.

Efficient drug delivery is crucial for glaucoma patients. Flexible biomedical devices that enable sustained ocular drug delivery and can regulate the drug release rate according to physiological conditions are highly desirable for glaucoma treatments, addressing both low drug bioavailability and poor patient compliance from manual drug administration, and improving treatment outcomes. Inspired by the structure and reciprocating motion of fish dorsal fins, a drug‐eluting contact lens based on deformable microstructures for non‐invasive ocular surface drug delivery is developed. Liquid drugs are stored within the interstices of the deformable microstructural units, allowing for continuous drug release through diffusion upon contact with the ocular surface. Finite element analysis is utilized to study the intraocular drug transport dynamics of glaucoma and optimize the overall layout of the device. Microstructural units undergo deformation under loading, altering the interstitial spaces and modulating the drug release rate. This device can adaptively adjust its drug release rate based on changes in intraocular pressure (IOP) and can be proactively regulated in response to cyclic eye loads, accommodating elevated IOP caused by varying body postures and activities. As a flexible, non‐invasive, highly dynamic, and adaptive drug delivery platform, it holds significant potential for future biomedical applications.

Advances in Drug Delivery

Conventional ophthalmic systems present very low corneal systemic bioavailability due to the nasolacrimal drainage and the difficulty to deliver the drug in the posterior segment of ocular tissue. For these reasons, recent advances have focused on the development of new ophthalmic drug delivery systems. This review provides an insight into the various constraints associated with ocular drug delivery, summarizes recent findings in soft contact lenses (SCL) and the applications of novel pharmaceutical systems for ocular drug delivery. Among the new therapeutic approaches in ophthalmology, SCL are novel continuous-delivery systems, providing high and sustained levels of drugs to the cornea. The tendency of research in ophthalmic drug delivery systems development are directed towards a combination of several technologies (bio-inspired and molecular imprinting techniques) and materials (cyclodextrins, surfactants, specific monomers). There is a tendency to develop systems which not only prolong the contact time of the vehicle at the ocular surface, but also at the same time slow down the clearance of the drug. Different materials can be applied during the development of contact lenses and can be combined with natural inspired strategies of drug immobilization and release, providing successful tools for ocular drug delivery systems.

A comprehensive review on contact lens for ophthalmic drug delivery