​Systemic anti-inflammatory therapy to prevent or delay diabetic cataracts and treat post-surgical inflammation

​Currently, surgical intervention is the only cure for cataracts, though this can be complicated in patients with diabetes. One of the most common postoperative complications in patients suffering from diabetes is persistent inflammation (uveitis) that can cause significant corneal edema, posterior synechia, and progression of diabetic retinopathy or neovascular glaucoma. There is substantial evidence that secondary cataract formation due to health conditions such as diabetes are associated with increased inflammation, oxidative stress, and sorbitol accumulation, along with covalent bonding of a protein or lipid molecule with a sugar molecule causing an increase in advanced glycosylation end products (AGE) formation that can cause significant damage to cells and tissues. The efforts to combat these effects using traditional drugs often leads to severe side effects outweighing the benefits. On the other hand natural compounds such as curcumin offer promise, but their progress is hampered due to lack of suitable dosage forms and poor bioavailability. In order to overcome inferior physicochemical and pharmacological attributes of curcumin we have prepared biodegradable nanosystems of polylactide-co-glycolide (PLGA) encapsulating curcumin (nCUR). These passively absorbed nCUR when given 8 mg/kg/day were significantly more effective than plain curcumin in delaying diabetic cataract in rodents, independent of glucose reduction. Despite the enhanced performance of passive nCUR, a significant dose remained unabsorbed in the intestine, indicating potential for further improvement through active-nanosystems. For the first time, we present a non-competitive active transport strategy to improve drug transport across biological barriers by developing carrier systems that have no equivalent in the world of competitive ligands. ​In this project, we will continue our studies on non-competitive active drug delivery strategy and understand how the systemic anti-inflammatory therapy will prevent or delay diabetic cataracts and manage intraocular inflammation in rodent and canine models respectively. 

Publications

  1. R. Ganugula, M. Arora, S. Dwivedi, D. S. Chandrashekar, S. Varambally, E. M. Scott, M. N. V. Ravi Kumar. Systemic Anti-Inflammatory Therapy Aided by Curcumin-Laden Double-Headed Nanoparticles Combined with Injectable Long-Acting Insulin in a Rodent Model of Diabetes Eye Disease.   ACS Nano 17: 6857-6874, 2023.
  2. R. Ganugula, M. Arora, M. A. Lepiz, Y. Niu, B. K. Mallick, S. C. Pflugfelder, E. M. Scott, M. N. V. Ravi Kumar. Systemic anti-inflammatory therapy aided by double-headed nanoparticles in a canine model of acute intraocular inflammation. Sci. Adv. 6: eabb7878, 2020. 
  3. M. Arora, R. Ganugula, N. Kumar, G. Kaur, J.-P. Pellois, P. Garg, M. N. V. Ravi Kumar. Next-generation non-competitive nanosystems based on gambogic acid: in silico identification of transferrin receptor binding sites, regulatory shelf-stability and their preliminary safety in healthy rodents ACS Appl. Bio Mater.  2: 3540-3550, 2019 (Cover article) 
  4. G. Kaur, M. Arora, R. Ganugula and M. N. V. Ravi Kumar. Double-headed nanosystems for oral drug delivery. Chem Comm. 55: 4761-4764, 2019  [Cover article, back cover]