Organic Chemistry Seminar – Ananya Biswas

About the event

Speaker: Ananya Biswas

Group: Sharma Lab (PI- Dr. Anjali Sharma)

Title: Dendrimer-Mediated Corneal Drug Delivery: Bridging Anatomical Barriers to Translational Therapeutics

Abstract

The eye presents a uniquely complex anatomical and physiological environment that significantly limits the effective delivery of therapeutics to ocular tissues. The human cornea, while accessible for topical administration, possesses multiple protective barriers that restrict drug penetration and limit the therapeutic efficacy of conventional ophthalmic formulations. Topical administration (eye drops), accounting for 90% of all ophthalmic formulations, remains the preferred clinical route owing to its noninvasiveness, ease of self-administration, and minimal systemic exposure, but its efficacy is fundamentally limited by rapid precorneal clearance and poor epithelial permeation. As a result, many ocular diseases require frequent dosing or invasive interventions, which can compromise patient compliance and therapeutic outcomes. These challenges highlight the need for innovative drug delivery strategies capable of overcoming corneal barriers while maintaining safety and sustained therapeutic activity.

Nanotechnology, and dendrimers in particular, offer a rational solution: their generation-dependent branched architecture, multivalent surface chemistry, and tunable polarity allow simultaneous enhancement of corneal residence time, transcellular permeation, and controlled drug release. In particular, polyamidoamine (PAMAM) dendrimers have demonstrated excellent biocompatibility and the capacity to enhance drug solubility, tissue penetration, and targeted delivery to diseased ocular tissues. Recent advances have shown that dendrimer-drug conjugates can facilitate sustained corneal retention, improved epithelial permeability, and selective accumulation at sites of inflammation and neovascularization. The translational relevance of PAMAM dendrimer platform is directly demonstrated by clinical products, D-4517.2 and D-NAC which are G4-PAMAM-OH conjugates of an anti-VEGF sunitinib analog and N-acetyl cysteine, respectively, undergoing clinical trials for ocular neovascularization and inflammation.

This talk will highlight the design and translational potential of dendrimer-based nanotherapeutics for corneal drug delivery. We will discuss strategies for engineering dendrimer platforms to overcome ocular barriers, enhance therapeutic bioavailability, and enable targeted treatment of corneal diseases such as inflammation, infection, and pathological neovascularization. Emphasis will be placed on how rational nanoscale engineering of dendrimer surfaces can improve pharmacokinetics, reduce systemic exposure, and support clinically translatable ophthalmic therapies.