Pharmaceutical Department, College of Pharmacy, Texas A&M University-College Station

Pharmaceutical Department, College of Pharmacy, Texas A&M University-College Station

My Postdoctoral research involved the design and synthesis of smart polymer nanoparticles for oral drug delivery applications for autoimmune diseases such as diabetes, diabetic retinopathy and lupus.

Projects

Next-Generation Noncompetitive Nanosystems Based on Gambogic Acid: In Silico Identification of Transferrin Receptor Binding Sites, Regulatory Shelf Stability, and Their Preliminary Safety in Healthy Rodents

A major challenge in drug delivery is to enhance the transport of drugs across biological barriers, such as the small intestine, the blood–brain barrier, and the blood–retinal/ocular barrier, and to effectively reach the site of action while minimizing the systemic impact. In recent years, piggybacking cell surface receptors have been considered a viable strategy for active drug delivery across the biological barriers. However, the ligands used to target drugs to plasma membrane receptors often have to compete against endogenous ligands, thereby limiting their binding to the cell surface and their transport across barriers. To address this problem, gambogic acid (GA) was identified as a noncompetitive ligand specific to the transferrin receptor (TfR), a receptor present on various barriers. However, the binding sites of the GA on TfR remain unknown, an essential step toward establishing structure–activity relationships. In silico binding site prediction tools, blind docking, and molecular docking simulation confirm that the GA binding site on the TfR is independent of the transferrin-bound iron binding sites. The GA-conjugated polyesters were processed into nanoparticles suitable for drug delivery applications that possess excellent storage stability under regulatory conditions.

Oral Drug Delivery Technologies—A Decade of Developments

Advanced drug delivery technologies, in general, enable drug reformulation and administration routes, together contributing to life-cycle management and allowing the innovator to maintain the product monopoly. Over the years, there has been a steady shift from mere life-cycle management to drug repurposing—applying delivery technologies to tackle solubility and permeability issues in early stages or safety and efficacy issues in the late stages of drug discovery processes. While the drug and the disease in question primarily drive the choice of route of administration, the oral route, for its compliance and safety attributes, is the most preferred route, particularly when it comes to chronic conditions, including pain, which is not considered a disease but a symptom of a primary cause. Therefore, the attempt of this review is to take a stock of the advances in oral delivery technologies that are applicable for injectable to oral transformation, improve risk-benefit profiles of existing orals, and apply them in the early discovery program to minimize the drug attrition rates.

Double-headed nanosystems for oral drug delivery

We demonstrate a novel strategy to engineer double-headed nanosystems by chemical modification of the carboxyl terminal polyester with a linker that offers tripodal arrangement of ligands on the particle surfaces. The in vivo results suggest that the bioavailability of encapsulated curcumin is proportional to the ligand density rendered by double-headed nanosystems.