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Optimising PLGA-PEG nanoparticle size and distribution for enhanced drug targeting to the inflamed intestinal barrier

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journal contribution
posted on 02.07.2021, 15:01 by Lauren Mohan, Lauren McDonald, Jacqueline Daly, Zebunnissa Ramtoola
Oral nanomedicines are being investigated as an innovative strategy for targeted drug delivery to treat inflammatory bowel diseases. Preclinical studies have shown that nanoparticles (NPs) can preferentially penetrate inflamed intestinal tissues, allowing for targeted drug delivery. NP size is a critical factor affecting their interaction with the inflamed intestinal barrier and this remains poorly defined. In this study we aimed to assess the impact of NP particle size (PS) and polydispersity (PDI) on cell interaction and uptake in an inflamed epithelial cell model. Using 10, 55 and 100 mg/mL poly(lactic-co-glycolic acid)-polyethylene glycol (PLGA-PEG), NPs of 131, 312 and 630 nm PS, respectively, were formulated by solvent dispersion. NP recovery was optimised by differential centrifugation to yield NPs of decreased and unimodal size distribution. NP-cell interaction was assessed in healthy and inflamed caco-2 cell monolayers. Results show that NP interaction with caco-2 cells increased with increasing PS and PDI and was significantly enhanced in inflamed cells. Trypan blue quenching revealed that a significant proportion of multimodal NPs were primarily membrane bound, while monomodal NPs were internalized within cells. These results are interesting as the PS and PDI of NPs can be optimised to allow targeting of therapeutic agents to the epithelial membrane and/or intracellular targets in the inflamed intestinal epithelium.

Funding

RCSI University of Medicine and Health Sciences Biology PhD Scholarship program

History

Comments

The original article is available at https://www.mdpi.com/

Published Citation

Mohan LJ, McDonald L, Daly JS, Ramtoola Z. Optimising PLGA-PEG nanoparticle size and distribution for enhanced drug targeting to the inflamed intestinal barrier. Pharmaceutics. 2020 12(11):1114.

Publication Date

19 Nov 2020

PubMed ID

33228175

Department/Unit

  • Anatomy and Regenerative Medicine
  • School of Pharmacy and Biomolecular Sciences

Research Area

  • Vascular Biology
  • Health Professions Education
  • Chemistry and Pharmaceutical Sciences
  • Immunity, Infection and Inflammation
  • Biomaterials and Regenerative Medicine

Publisher

MDPI AG

Version

  • Published Version (Version of Record)