Transport System Opens Door To More Drugs Given Orally with Better Brain Penetration Interview with:

M. N. V. Ravi Kumar PhD Professor of Pharmaceutical Sciences Texas A&M Rangel College of Pharmacy

Dr. M. N. V. Ravi Kumar

M. N. V. Ravi Kumar PhD
Professor of Pharmaceutical Sciences
Texas A&M Rangel College of Pharmacy What is the background for this study? What are the main findings?

Response: The use of ligands for receptor-mediated drug delivery offers potential for improving both the safety and efficacy of pharmaceuticals. Research to date, however, has yet to overcome some of the significant challenges of targeted drug delivery, one of which is competitive affinity with endogenous ligands. This competition for the receptor binding site can impair both natural cell processes and uptake of the drug complex across the cell wall.

This article presents a unique, non-competitive active transport strategy for crossing the intestinal barrier. Gambogic acid (GA), as a ligand, was coupled with a polymer called poly(lactic-co–glycolic acid) (PLGA) that in turn can encapsulate drugs forming nanosystems to bind to transferrin receptors within the intestinal wall, which facilitated active gut barrier crossing. The study results show peak plasma concentrations of Cyclosporine A (CsA) in orally dosed rodents at 6 hours with the GA-ladened nanosystems vs 24 hours without GA. Additionally, brain concentrations of CsA are twice as high dosing with PLGA-GA NS compared with PLGA-NS (without GA). What should readers take away from your report?

Response: These results offer capabilities in two distinct areas.

  • First, GA as a targeting agent, enhances the ability of the nanosystem to cross the gut barrier, enter the circulatory system, achieve optimal therapeutic concentration, and remain bioavailable within prescribed safety levels. This suggests an ability to orally deliver sparingly water-soluble and insoluble compounds in a controlled manner, thereby improving drug efficacy, safety, patient compliance and/or cost of care versus IV administration. Applying this technology in conjunction with drug compounds known to be difficult to deliver orally could open the door to more beneficial care.
  • Second, the GA-ladened nanosystems show improved ability to cross the blood-brain barrier, with the potential to achieve desirable therapeutic levels of CsA within the brain tissue. What recommendations do you have for future research as a result of this study?

Response: This represents an opportunity to conquer one of the most significant challenges in pharmaceutical drug targeting namely, crossing the blood-brain-barrier. Testing the cyclosporine formulation developed in this study in traumatic brain injury is a logical next step.

Further, evaluating this technology with known drugs for assessing the potential to improve the treatment of some of today’s most prevalent neurological and psychiatric conditions, e.g., Alzheimer’s, Parkinson’s, Multiple Sclerosis, Stroke, Glioblastoma, epilepsy. Is there anything else you would like to add?

Response: This technology can be applied to a majority of poorly soluble and permeable compounds that constitute about 40% of the new chemical entities, posing a major challenge for formulation scientist. Another significant area that this technology can be applied is in cancer therapy. Metronomic therapy (MET) or semi-MET regimen usually administers chemotherapeutics at low doses more frequently (2-3 times/week). This method is emerging as an alternative to traditional maximum tolerated dose (MTD) regimens administered every 3 weeks for 3-8 cycles. However, MET with an injectable paclitaxel (PTX) makes it very difficult to patients coming in to clinic at weekly or more frequent visits, so to make it more patient friendly, we need an orally bioavailable PTX, which can be realized by the proposed systems. Thank you for your contribution to the community.


The Next Generation Non-competitive Active Polyester Nanosystems for Transferrin Receptor-mediated Peroral Transport Utilizing Gambogic Acid as a Ligand
P. Saini, R. Ganugula, M. Arora & M. N. V. Ravi Kumar
Scientific Reports 6, Article number: 29501 (2016)

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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