Below, find all the information on articles and publications from the ORBITAL Early Stage Researchers.

  • Ocular Disorders and Associated Drug Development Challenges: The Current Scenario
    D. Mishra, S. Gade, T. R. R. Singh, Ocular Disorders and Associated Drug Development Challenges: The Current Scenario (2020).

    • Vision is one of the most important human sense and hence eye diseases leading to impairment of vision have been the hot topic for drug delivery research lately. Diseases like glaucoma, cataract, age-related macular degeneration, diabetic retinopathy and trachomatous trichiasis have been known for their potential of visual impairment as well as blindness. A vast amount of research has been done in understanding the pathophysiology, risk factors and drug development and drug delivery challenges associated with these diseases, but the clinical success achieved so far is very sparse. This leading to the requirements for the better understanding of the ocular diseases which can be translated to better drug delivery systems. The current review is formulated with the aims to provide a concise summary of these ocular disorders and to address the challenges in their drug development research.
  • Therapeutic Ophthalmic Lenses: A Review
    Toffoletto, N.; Saramago, B.; Serro, A.P. Therapeutic Ophthalmic Lenses: A Review. Pharmaceutics 2021, 13, 36.

    • An increasing incidence of eye diseases has been registered in the last decades in developed countries due to the ageing of population, changes in lifestyle, environmental factors, and the presence of concomitant medical conditions. The increase of public awareness on ocular conditions leads to an early diagnosis and treatment, as well as an increased demand for more effective and minimally invasive solutions for the treatment of both the anterior and posterior segments of the eye. Despite being the most common route of ophthalmic drug administration, eye drops are associated with compliance issues, drug wastage by lacrimation, and low bioavailability due to the ocular barriers. In order to overcome these problems, the design of drug-eluting ophthalmic lenses constitutes a non-invasive and patient-friendly approach for the sustained drug delivery to the eye. Several examples of therapeutic contact lenses and intraocular lenses have been developed, by means of different strategies of drug loading, leading to promising results. This review aims to report the recent advances in the development of therapeutic ophthalmic lenses for the treatment and/or prophylaxis of eye pathologies (i.e., glaucoma, cataract, corneal diseases, or posterior segment diseases) and it gives an overview of the future perspectives and challenges in the field.
  • Penetration Enhancers for Topical Drug Delivery to the Ocular Posterior Segment—A Systematic Review
    Thareja, A.; Hughes, H.; Alvarez-Lorenzo, C.; Hakkarainen, J.J.; Ahmed, Z. Penetration Enhancers for Topical Drug Delivery to the Ocular Posterior Segment—A Systematic Review. Pharmaceutics 2021, 13, 276. https://doi.org/10.3390/pharmaceutics13020276

    • There is an unmet clinical need for eye drop formulations to efficiently treat the diseases of the posterior ocular segment by non-invasive topical administration. Here, we systematically reviewed the literature on ocular penetration enhancers and their ability to transfer drugs to the posterior segment of the eye in experimental studies. Our aim was to assess which penetration enhancer is the most efficient at delivering drugs to the posterior segment of the eye, when topically applied. We conducted a comprehensive search in three electronic databases (Ovid Embase, Ovid MEDLINE, and PubMed) to identify all the relevant manuscripts reported on ocular penetration enhancers based on the PRISMA guidelines. We identified 6540 records from our primary database search and filtered them per our inclusion/exclusion criteria to select a final list of 14 articles for qualitative synthesis. Of these, 11 studies used cell penetrating peptides (CPPs), 2 used chitosan, and 1 used benzalkonium chloride (BAC) as the penetration enhancer. Cationic and amphipathic CPPs, transactivator of transcription (TAT), and penetratin can be inferred to be the best among all the identified penetration enhancers for drug delivery to the fundus oculi via topical eye drop instillation. Further high-quality experimental studies are required to ascertain their quantitative efficacy.
  • Lipid-Based Nanocarriers for Ophthalmic Administration: Towards Experimental Design Implementation
    González-Fernández, F.M.; Bianchera, A.; Gasco, P.; Nicoli, S.; Pescina, S. Lipid-Based Nanocarriers for Ophthalmic Administration: Towards Experimental Design Implementation. Pharmaceutics 2021, 13, 447. https://doi.org/10.3390/pharmaceutics13040447

    • Nanotherapeutics based on biocompatible lipid matrices allow for enhanced solubility of poorly soluble compounds in the treatment of ophthalmic diseases, overcoming the anatomical and physiological barriers present in the eye, which, despite the ease of access, remains strongly protected. Micro-/nanoemulsions, solid lipid nanoparticles (SLN) or nanostructured lipid carriers (NLC) combine liquid and/or solid lipids with surfactants, improving drug stability and ocular bioavailability. Current research and development approaches based on try-and-error methodologies are unable to easily fine-tune nanoparticle populations in order to overcome the numerous constraints of ocular administration routes, which is believed to hamper easy approval from regulatory agencies for these systems. The predictable quality and specifications of the product can be achieved through quality-by-design (QbD) implementation in both research and industrial environments, in contrast to the current quality-by-testing (QbT) framework. Mathematical modelling of the expected final nanoparticle characteristics by variation of operator-controllable variables of the process can be achieved through adequate statistical design-of-experiments (DoE) application. This multivariate approach allows for optimisation of drug delivery platforms, reducing research costs and time, while maximising the understanding of the production process. This review aims to highlight the latest efforts in implementing the design of experiments to produce optimised lipid-based nanocarriers intended for ophthalmic administration. A useful background and an overview of the different possible approaches are presented, serving as a starting point to introduce the design of experiments in current nanoparticle research.
  • Microneedle array systems for long-acting drug delivery
    Lalit K. Vora, Kurtis Moffatt, Ismaiel A. Tekko, Alejandro J. Paredes, Fabiana Volpe-Zanutto, Deepakkumar Mishra, Ke Peng, Raghu Raj Singh Thakur, Ryan F. Donnelly, Microneedle array systems for long-acting drug delivery, European Journal of Pharmaceutics and Biopharmaceutics, Volume 159, 2021, Pages 44-76, ISSN 0939-6411,
    https://doi.org/10.1016/j.ejpb.2020.12.006.

    • The development of microneedles (MNs) assisted drug delivery technologies have been highly active for more than two decades. The minimally invasive and self-administered MN technology bypasses many challenges associated with injectable drug delivery systems, by delivering the therapeutic materials directly into the dermal and ocular space and allowing the release of the active ingredient in a sustained or controlled manner. Different types of MNs (biodegradable solid/dissolving MNs and nanoparticle loaded/coated polymeric MNs or delivery by hollow MNs) have been envisioned for long-acting sustained delivery of therapeutic payloads, with the aim of reducing the side effects and administration frequency to improve the patient compliance. In this review, we covered the different types of MNs loaded with different nano/biotherapeutics for long-acting delivery for a wide range of potential clinical applications. We also outlined the future development scenario of such long-acting MN delivery systems for different disease conditions to achieve improved clinical benefit. Finally, we discussed the challenges lie ahead to realize the full potential of sustained-release long-acting MNs in the clinic.
  • Atorvastatin-Eluting Contact Lenses: Effects of Molecular Imprinting and Sterilization on Drug Loading and Release
    Pereira-da-Mota, A.F.; Vivero-Lopez, M.; Topete, A.; Serro, A.P.; Concheiro, A.; Alvarez-Lorenzo, C. Atorvastatin-Eluting Contact Lenses: Effects of Molecular Imprinting and Sterilization on Drug Loading and Release. Pharmaceutics 2021, 13, 606. https://doi.org/10.3390/pharmaceutics13050606

    • Statins are receiving increasing attention in the ophthalmic field. Their activity as 3-hydroxy-3-methylglutaryl–CoA (HMG–CoA) reductase inhibitors is clinically used to regulate cholesterol levels and leads to pleiotropic effects, which may help in the management of diabetes-related ocular pathologies. This work aims to design bioinspired contact lenses (CLs) with an affinity for atorvastatin by mimicking the active site of HMG–CoA reductase. Sets of imprinted and nonimprinted 2-hydroxyethyl methacrylate (HEMA) hydrogels were synthesized, varying the contents in functional monomers that bear chemical groups that resemble those present in HMG–CoA reductase, namely, ethylene glycol phenyl ether methacrylate (EGPEM), 2-aminoethyl methacrylate hydrochloride (AEMA), and N-(3-aminopropyl) methacrylamide hydrochloride (APMA). The hydrogels were characterized in terms of suitability as CLs (solvent uptake, light transmission, mechanical properties, and biocompatibility) and capability to load and release atorvastatin. Three sterilization protocols (steam heat, gamma radiation, and high hydrostatic pressure) were implemented and their effects on hydrogel properties were evaluated. Copolymerization of AEMA and, particularly, APMA endowed the hydrogels with a high affinity for atorvastatin (up to 11 mg/g; KN/W > 200). Only high hydrostatic pressure sterilization preserved atorvastatin stability and hydrogel performance. Permeability studies through the porcine cornea and sclera tissues revealed that the amount of atorvastatin accumulated in the cornea and sclera could be effective to treat ocular surface diseases.

 

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