Development, Optimization, and Clinical Relevance of Lactoferrin Delivery Systems: A Focus on Ocular Delivery.

Lactoferrin (Lf), a multifunctional protein found abundantly in secretions, including tears, plays a crucial role in ocular health through its antimicrobial, immunoregulatory, anti-inflammatory, and antioxidant activities. Advanced delivery systems are desirable to fully leverage its therapeutic potential in treating ocular diseases. The process of Lf quantification for diagnostic purposes underscores the importance of developing reliable, cost-effective detection methods, ranging from conventional techniques to advanced nano-based sensors. Despite the ease and non-invasiveness of topical administration for ocular surface diseases, challenges such as rapid drug elimination necessitate innovations, such as Lf-loaded contact lenses and biodegradable polymeric nanocapsules, to enhance drug stability and bioavailability. Furthermore, overcoming ocular barriers for the treatment of posterior segment disease calls for nano-formulations. The scope of this review is to underline the advancements in nanotechnology-based Lf delivery methods, emphasizing the pivotal role of multidisciplinary approaches and cross-field strategies in improving ocular drug delivery and achieving better therapeutic outcomes for a wide spectrum of eye conditions.

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

Posterior segment diseases, such as age-related macular degeneration (AMD) and diabetic retinopathy (DR) are vital factor that seriously threatens human vision health and quality of life, the treatment of which poses a great challenge to ophthalmologists and ophthalmic scientists. In particular, ocular posterior drug delivery in a non-invasive manner is highly desired but still faces many difficulties such as rapid drug clearance, limited permeability and low drug accumulation at the target site. At present, many novel non-invasive topical ocular drug delivery systems are under development aiming to improve drug delivery efficiency and biocompatibility for better therapy of posterior segment oculopathy. The purpose of this review is to present the challenges in the noninvasive treatment of posterior segment diseases, and to propose strategies to tackle these bottlenecks. First of all, barriers to ocular administration were introduced based on ocular physiological structure and behavior, including analysis and discussion on the influence of ocular structures on noninvasive posterior segment delivery. Thereafter, various routes of posterior drug delivery, both invasive and noninvasive, were illustrated, along with the respective anatomical obstacles that need to be overcome. The widespread and risky application of invasive drug delivery, and the need to develop non-invasive local drug delivery with alternative to injectable therapy were described. Absorption routes through topical administration and strategies to enhance ocular posterior drug delivery were then discussed. As a follow-up, an up-to-date research advances in non-invasive delivery systems for the therapy of ocular fundus lesions were presented, including different nanocarriers, contact lenses, and several other carriers. In conclusion, it seems feasible and promising to treat posterior oculopathy via non-invasive local preparations or in combination with appropriate devices.

Innovative Strategies for Drug Delivery to the Ocular Posterior Segment.

Innovative and new drug delivery systems (DDSs) have recently been developed to vehicle treatments and drugs to the ocular posterior segment and the retina. New formulations and technological developments, such as nanotechnology, novel matrices, and non-traditional treatment strategies, open new perspectives in this field. The aim of this mini-review is to highlight promising strategies reported in the current literature based on innovative routes to overcome the anatomical and physiological barriers of the vitreoretinal structures. The paper also describes the challenges in finding appropriate and pertinent treatments that provide safety and efficacy and the problems related to patient compliance, acceptability, effectiveness, and sustained drug delivery. The clinical application of these experimental approaches can help pave the way for standardizing the use of DDSs in developing enhanced treatment strategies and personalized therapeutic options for ocular pathologies.

Neuroprotective Nanoparticles Targeting the Retina: A Polymeric Platform for Ocular Drug Delivery Applications.

Neuroprotective drug delivery to the posterior segment of the eye represents a major challenge to counteract vision loss. This work focuses on the development of a polymer-based nanocarrier, specifically designed for targeting the posterior eye. Polyacrylamide nanoparticles (ANPs) were synthesised and characterised, and their high binding efficiency was exploited to gain both ocular targeting and neuroprotective capabilities, through conjugation with peanut agglutinin (ANP:PNA) and neurotrophin nerve growth factor (ANP:PNA:NGF). The neuroprotective activity of ANP:PNA:NGF was assessed in an oxidative stress-induced retinal degeneration model using the teleost zebrafish. Upon nanoformulation, NGF improved the visual function of zebrafish larvae after the intravitreal injection of hydrogen peroxide, accompanied by a reduction in the number of apoptotic cells in the retina. Additionally, ANP:PNA:NGF counteracted the impairment of visual behaviour in zebrafish larvae exposed to cigarette smoke extract (CSE). Collectively, these data suggest that our polymeric drug delivery system represents a promising strategy for implementing targeted treatment against retinal degeneration.

A novel dendrimer-based complex co-modified with cyclic RGD hexapeptide and penetratin for noninvasive targeting and penetration of the ocular posterior segment.

Noninvasive drug delivery is a promising treatment strategy for ocular posterior segment diseases. Many physiological and anatomical barriers of the eye considerably restrict effective diffusion of therapeutics to the target site. To overcome this problem, a novel cyclic arginine-glycine-aspartate (RGD) hexapeptide and penetratin (PEN) co-modified PEGylation polyamidoamine (PAMAM) was designed as a nanocarriers (NCs), and its penetrating and targeting abilities were evaluated. In this study, we show that PAMAM-PEG (reaction molar ratio 1:32) has a relatively high grafting efficiency and low cytotoxicity. The particle size was within the range of 15-20 nm after modification with RGD and PEN. Cellular uptake of RGD-modified NCs involved significant affinity toward integrin αvß3, which validated the targeting of neovasculature. An in vitro permeation study indicated that modification with PEN significantly improved penetration of the NCs (1.5 times higher). In vivo ocular distribution studies showed that, the NCs (modified with PEN or co-modified with RGD and PEN) were highly distributed in the cornea and retina (p < .001), and modification extended retinal retention time for more than 12 h. Therefore, these NCs appear to be a promising noninvasive ocular drug delivery system for ocular posterior segment diseases.