Recent advances in nanocrystal-based technologies applied for ocular drug delivery.

INTRODUCTION: The intricate physiological barriers of the eye and the limited volume of eye drops impede efficient delivery of poorly water-soluble drugs. In the last decade, nanocrystals have emerged as versatile drug delivery systems in various administration routes from bench to bedside. The unique superiorities of nanocrystals, mainly embodied in high drug-loading capacity, good mucosal adhesion and penetration, and greatly improved drug solubility, reveal a promising prospect for ocular delivery of poorly water-soluble drugs. AREAS COVERED: This article focuses on the ophthalmic nanocrystal technologies and products that are in the literature, clinical trials, and even on the market. The recent research progress in the preparation, ocular application, and absorption of nanocrystals are highlighted, and the pros and cons of nanocrystals in overcoming the physiological barriers of the eye are also summarized. EXPERT OPINION: Nanocrystals have demonstrated success as glucocorticoid eye drops in the treatment of anterior segment diseases. However, the thermodynamic stability of nanocrystals remains the major challenge in product development. New technologies for efficiently optimizing stabilizers and sterilization processes are still expected. Strategies to confer more diverse functions via surface modification are also worth exploration to improve the potential of nanocrystals in delivering poorly water-soluble drugs to posterior segment of the eye.

Ocular therapies with biomacromolecules: From local injection to eyedrop and emerging noninvasive delivery strategies.

The last two decades have witnessed a continuously increasing number of biomacromolecules approved for the treatment of ocular diseases. The eye possesses multiple protective mechanisms to resist the invasion of exogenous substances, but meanwhile these physiological defense systems also act as strong barriers, impeding absorption of most biomacromolecules into the eye. As a result, local injections play predominant roles for posterior ocular delivery of biomacromolecules in clinical practice. To achieve safe and convenient application of biomacromolecules, alternative strategies to realize noninvasive intraocular delivery are necessary. Various nanocarriers, novel penetration enhancers and physical strategies have been explored to facilitate delivery of biomacromolecules to both anterior and posterior ocular segments but still suffered difficulties in clinical translation. This review compares the anatomical and physiological characteristics of the eyes from those frequently adopted experimental species and profiles the well-established animal models of ocular diseases. We also summarize the ophthalmic biomacromolecules launched on the market and put emphasis on emerging noninvasive intraocular delivery strategies of peptides, proteins and genes.

Tumor microenvironment remodeling-based penetration strategies to amplify nanodrug accessibility to tumor parenchyma.

Remarkable advances in nano delivery systems have provided new hope for tumor prevention, diagnosis and treatment. However, only limited clinical therapeutic effects against solid tumors were achieved. One of the main reasons is the presence of abundant physiological and pathological barriers in vivo that impair tumoral penetration and distribution of the nanodrugs. These barriers are related to the components of tumor microenvironment (TME) including abnormal tumor vasculature, rich composition of the extracellular matrix (ECM), and abundant stroma cells. Herein, we review the advanced strategies of TME remodeling to overcome these biological obstacles against nanodrug delivery. This review aims to offer a perspective guideline for the implementation of promising approaches to facilitate intratumoral permeation of nanodrugs through alleviation of biological barriers. At the same time, we analyze the advantages and disadvantages of the corresponding methods and put forward possible directions for the future researches.

Nanoporous hollow transition metal chalcogenide nanosheets synthesized via the anion-exchange reaction of metal hydroxides with chalcogenide ions.

Nanoporous hollow transition metal chalcogenides are of special interest for a variety of promising applications. Although some advanced synthetic methods have been reported, the development of a facile and general strategy to fabricate porous hollow nanostructures of transition metal chalcogenides, especially with enhanced electrocatalytic performance, still remains highly challenged. Herein, we report a facile chemical transformation strategy to prepare nanoporous hollow Co3S4 nanosheets via the anion exchange reaction of Co(OH)2 with sulfide ions. The chemical transformation mechanism involves the as-formed layer of nanoporous cobalt sulfide on Co(OH)2 driven by the anion-exchange-reaction and lattice mismatch induced quick strain release, a following diffusion-effect-dominated core-shell hollow intermediate with hollow interiors, and subsequent Ostwald ripening growth of hollow nanosheets at elevated temperatures. This anion-exchange strategy of transition metal hydroxides with chalcogenide ions is also suitable for fabricating nanoporous hollow nanosheets of other metal chalcogenides (e.g., CoSe2, CoTe2, CdS, and NiS). The as-prepared nanoporous hollow Co3S4 nanosheets are found to be highly active and stable for electrocatalytic oxygen evolution reaction.