Chitosan modified 5-fluorouracil nanostructured lipid carriers for treatment of diabetic retinopathy in rats: A new dimension to an anticancer drug

Sharma DS 1 , Wadhwa S 2 , Gulati M 3 , Kumar B 1 , Chitranshi N 4 , Gupta VK 4 Show all authors , Alrouji M 5 , Alhajlah S 5 , AlOmeir O 6 , Vishwas S 1 , Khursheed R 1 , Saini S 1 , Kumar A 1 , Parveen SR 1 , Gupta G 7 , Zacconi F 8 , Chellappan DK 9 , Morris A 10 , Loebenberg R 11 , Dua K 12 , Singh SK 13

Affiliations 

  • 1 School of Pharmaceutical Sciences, Lovely Professional University, Phagwara 144411, Punjab, India
  • 2 School of Pharmaceutical Sciences, Lovely Professional University, Phagwara 144411, Punjab, India. Electronic address: sheetupharma@gmail.com
  • 3 School of Pharmaceutical Sciences, Lovely Professional University, Phagwara 144411, Punjab, India; Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, Australia
  • 4 Faculty of Medicine, Health and Human Sciences, Macquarie University, North Ryde, Australia
  • 5 Department of Medical Laboratories, College of Applied Medical Sciences, Shaqra University, Shaqra 11961, Saudi Arabia
  • 6 Department of Pharmacy Practice, College of Pharmacy, Shaqra University, Shaqra 11961, Saudi Arabia
  • 7 School of Pharmacy, Suresh Gyan Vihar University, Mahal Road, Jagatpura, Jaipur, India; Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India; Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India
  • 8 Facultad de Química y de Farmacia, Pontificia Universidad Católica de Chile, Santiago 7820436, Chile; Institute for Biological and Medical Engineering, Schools of Engineering, Medicine and Biological Sciences, Pontificia Universidad Católica de Chile, Santiago 7820436, Chile
  • 9 Department of Life Sciences, School of Pharmacy, International Medical University, Bukit Jalil, 57000 Kuala Lumpur, Malaysia
  • 10 Swansea University Medical School, Swansea University, Singleton Park, Room 262, 1st Floor, Grove Building, Swansea, Wales SA2 8PP, UK
  • 11 University of Alberta, Faculty of Pharmacy and Pharmaceutical Sciences, Edmonton AB T6G2N8, Alberta, Canada
  • 12 Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, Australia; Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Ultimo, NSW 2007, Australia
  • 13 School of Pharmaceutical Sciences, Lovely Professional University, Phagwara 144411, Punjab, India; Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, Australia. Electronic address: singhsachin23@gmail.com
Int J Biol Macromol, 2023 Jan 01;224:810-830.
PMID: 36302483 DOI: 10.1016/j.ijbiomac.2022.10.168

Abstract

Diabetic retinopathy (DR) is one of the chronic complications of diabetes. It includes retinal blood vessels' damage. If untreated, it leads to loss of vision. The existing treatment strategies for DR are expensive, invasive, and need expertise during administration. Hence, there is a need to develop a non-invasive topical formulation that can penetrate deep to the posterior segment of retina and treat the damaged retinal vessels. In addition, it should also provide sustained release. In recent years, novel drug delivery systems (NDDS) have been explored for treating DR and found successful. In this study, chitosan (CS) modified 5-Fluorouracil Nanostructured Lipid Carriers (CS-5-FU-NLCs) were prepared by modified melt emulsification-ultrasonication method and optimized by Box-Behnken Design. The size, polydispersity index, zeta potential and entrapment efficiency of CS-5-FU-NLCs were 163.2 ± 2.3 nm, 0.28 ± 1.52, 21.4 ± 0.5 mV and 85.0 ± 0.2 %, respectively. The in vitro drug release and ex vivo permeation study confirmed higher and sustained drug release in CS-5-FU-NLCs as compared to 5-FU solution. HET-CAM Model ensured the non-irritant nature of CS-5-FU-NLCs. In vivo ocular studies of CS-5-FU-NLCs confirmed antiangiogenic effect of 5-FU by CAM model and diabetic retinopathy induced rat model, indicating successful delivery of 5-FU to the retina.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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