pharmaceutics-12-01114-v2.pdf (5.12 MB)
Optimising PLGA-PEG nanoparticle size and distribution for enhanced drug targeting to the inflamed intestinal barrier
journal contributionposted on 2021-07-02, 15:01 authored by Lauren Mohan, Lauren McDonald, Jacqueline DalyJacqueline Daly, Zeibun 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.
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CommentsThe original article is available at https://www.mdpi.com/
Published CitationMohan 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 Date19 Nov 2020
- Anatomy and Regenerative Medicine
- School of Pharmacy and Biomolecular Sciences
- Vascular Biology
- Health Professions Education
- Chemistry and Pharmaceutical Sciences
- Immunity, Infection and Inflammation
- Biomaterials and Regenerative Medicine
- Published Version (Version of Record)