The purpose of this study was to determine corneal permeability and uptake in rabbit, porcine, and bovine corneas for twenty-five drugs using an N-in-1 (cassette) approach and relate these parameters to drug physicochemical properties and tissue thickness through quantitative structure permeability relationships (QSPRs). A twenty-five-drug cassette containing β-blockers, NSAIDs, and corticosteroids in solution at a micro-dose was exposed to the epithelial side of rabbit, porcine, or bovine corneas mounted in a diffusion chamber, and the corneal drug permeability and tissue uptake were monitored using an LC-MS/MS method. Data obtained were used to construct and evaluate over 46,000 quantitative structure–permeability (QSPR) models using multiple linear regression, and the best-fit models were cross-validated by Y-randomization. Drug permeability was generally higher in rabbit cornea and comparable between bovine and porcine corneas. Permeability differences between species could be explained in part by differences in corneal thickness. Corneal uptake between species correlated with a slope close to 1, indicating generally similar drug uptake per unit weight of tissue. A high correlation was observed between bovine, porcine, and rabbit corneas for permeability and between bovine and porcine corneas for uptake (R² ≥ 0.94). MLR models indicated that drug characteristics such as lipophilicity (LogD), heteroatom ratio (HR), nitrogen ratio (NR), hydrogen bond acceptors (HBA), rotatable bonds (RB), index of refraction (IR), and tissue thickness (TT) are of great influence on drug permeability and uptake. When data for all species along with thickness as a parameter was used in MLR, the best fit equation for permeability was Log (% transport/cm²·s) = 0.441 LogD − 8.29 IR + 8.357 NR − 0.279 HBA − 3.833 TT + 10.432 (R² = 0.826), and the best-fit equation for uptake was Log (%/g) = 0.387 LogD + 4.442 HR + 0.105 RB − 0.303 HBA − 2.235 TT + 1.422 (R² = 0.750). Thus, it is feasible to explain corneal drug delivery in three species using a single equation.

The deadly pandemic, coronavirus disease 2019 (COVID‐19), caused due to the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has paralyzed the world. Although significant methodological advances have been made in the field of viral detection/diagnosis with 251 in vitro diagnostic tests receiving emergency use approval by the US‐FDA, little progress has been made in identifying curative or preventive therapies. This review discusses the current trends and potential future approaches for developing COVID‐19 therapeutics, including repurposed drugs, vaccine candidates, immune‐modulators, convalescent plasma therapy, and antiviral nanoparticles/nanovaccines/combinatorial nanotherapeutics to surmount the pandemic viral strain. Many potent therapeutic candidates emerging via drug‐repurposing could significantly reduce the cost and duration of anti‐COVID‐19 drug development. Gene/protein‐based vaccine candidates that could elicit both humoral and cell‐based immunity would be on the frontlines to prevent the disease. Many emerging nanotechnology‐based interventions will be critical in the fight against the deadly virus by facilitating early detection and enabling target oriented multidrug therapeutics. The therapeutic candidates discussed in this article include remdesivir, dexamethasone, hydroxychloroquine, favilavir, lopinavir/ritonavir, antibody therapeutics like gimsilumab and TJM2, anti‐viral nanoparticles, and nanoparticle‐based DNA and mRNA vaccines.

Due to high structural flexibility, multidrug carrying capability, and tunable size, dendrimers have been used as suitable carriers for ophthalmic drug delivery. Drug molecules can be either encapsulated or chemically coupled to dendrimers. The nanoscopic size, spheroidal shape, and cationic surface of polyamidoamine (PAMAM) dendrimers promote their interaction with the cornea and result in prolonged precorneal retention. Dendrimers could be further cross‐linked to produce three‐dimensional hydrogel networks or dendrimer hydrogels (DH). The properties of the DH can be readily adjusted to maintain both fluidity and adhesiveness, making them suitable for developing topical ocular drug formulations. Micro‐/nano‐ sized DHs, that is, dendrimer micro‐/nano‐ gels, have unique properties such as ease of administration, large specific surface area for adhesion, and drug targeting functionalities, making them attractive for ophthalmic drug delivery. This perspective reports advances in PAMAM dendrimer based drug delivery systems including drug conjugates and micro‐ and nano‐ gels to enhance and sustain the delivery of multiple anti‐glaucoma drugs, Dendrimer and dendrimer gel‐derived drug delivery systems hold great potential as multifunctional topical drug delivery systems for the eye.