{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T20:06:15Z","timestamp":1782936375891,"version":"3.54.5"},"reference-count":32,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2020,12,19]],"date-time":"2020-12-19T00:00:00Z","timestamp":1608336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"King Abdulaziz University, Jeddah, Saudi Arabia","award":["IRKA 1002"],"award-info":[{"award-number":["IRKA 1002"]}]},{"name":"The Ministry of Higher Education in Saudi Arabia","award":["IRKA 1002"],"award-info":[{"award-number":["IRKA 1002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The expansion of nanotechnology for drug delivery applications has raised questions regarding the safety of nanoparticles (NPs) due to their potential for interacting at molecular and cellular levels. Although polymeric NPs for drug delivery are formulated using FDA-approved polymers such as lactide- and glycolide-based polymers, their interactions with blood constituents, remain to be identified. The aim of this study was to determine the impact of size-selected Poly-lactide-co-glycolide-polyethylene glycol (PLGA-PEG) NPs on platelet activity. The NPs of 113, 321, and 585 nm sizes, were formulated and their effects at concentrations of 0\u20132.2 mg\/mL on the activation and aggregation of platelet-rich plasma (PRP) were investigated. The results showed that NPs of 113 nm did not affect adenosine diphosphate (ADP)-induced platelet aggregation at any NP concentration studied. The NPs of 321 and 585 nm, at concentrations \u22650.25 mg\/mL, reduced ADP-activated platelet aggregation. The platelet activation profile remained unchanged in the presence of investigated NPs. Confocal microscopy revealed that NPs were attached to or internalised by platelets in both resting and activated states, with no influence on platelet reactivity. The results indicate minimal risks of interference with platelet function for PLGA-PEG NPs and that these NPs can be explored as nanocarriers for targeted drug delivery to platelets.<\/jats:p>","DOI":"10.3390\/ijms21249716","type":"journal-article","created":{"date-parts":[[2020,12,21]],"date-time":"2020-12-21T01:01:08Z","timestamp":1608512468000},"page":"9716","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["PLGA-PEG Nanoparticles Show Minimal Risks of Interference with Platelet Function of Human Platelet-Rich Plasma"],"prefix":"10.3390","volume":"21","author":[{"given":"Rana","family":"Bakhaidar","sequence":"first","affiliation":[{"name":"School of Pharmacy and Biomolecular Sciences, RCSI, University of Medicine and Health Sciences, D02 YN77 Dublin 2, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"O\u2019Neill","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Biomolecular Sciences, RCSI, University of Medicine and Health Sciences, D02 YN77 Dublin 2, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zebunnissa","family":"Ramtoola","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Biomolecular Sciences, RCSI, University of Medicine and Health Sciences, D02 YN77 Dublin 2, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.1021\/nn800275r","article-title":"Self-assembled lipid-polymer hybrid nanoparticles: A robust drug delivery platform","volume":"2","author":"Zhang","year":"2008","journal-title":"ACS Nano"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1111\/j.2042-7158.2010.01174.x","article-title":"Investigation of the interaction of biodegradable micro- and nanoparticulate drug delivery systems with platelets","volume":"63","author":"Ramtoola","year":"2011","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3657","DOI":"10.1016\/j.biomaterials.2010.01.065","article-title":"Effects of particle size and surface charge on cellular uptake and biodistribution of polymeric nanoparticles","volume":"31","author":"He","year":"2010","journal-title":"Biomaterials"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1016\/j.biomaterials.2008.12.013","article-title":"PLGA-lecithin-PEG core-shell nanoparticles for controlled drug delivery","volume":"30","author":"Chan","year":"2009","journal-title":"Biomaterials"},{"key":"ref_5","first-page":"283","article-title":"Long-Circulating and Target-Specific Nanoparticles: Theory to Practice","volume":"53","author":"Moghimi","year":"2001","journal-title":"Pharmacol. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3682","DOI":"10.1016\/j.biomaterials.2009.03.054","article-title":"The relationship between the antimicrobial effect of catheter coatings containing silver nanoparticles and the coagulation of contacting blood","volume":"30","author":"Stevens","year":"2009","journal-title":"Biomaterials"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"157","DOI":"10.3109\/17435390.2010.506250","article-title":"Silver nanoparticles enhance thrombus formation through increased platelet aggregation and procoagulant activity","volume":"5","author":"Jun","year":"2011","journal-title":"Nanotoxicology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"735","DOI":"10.2217\/nnm.09.65","article-title":"Platelet compatibility of PLGA, chitosan and PLGA-chitosan nanoparticles","volume":"4","author":"Li","year":"2009","journal-title":"Nanomedicine"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Bakhaidar, R., Green, J., Alfahad, K., Samanani, S., Moollan, N., O\u2019Neill, S., and Ramtoola, Z. (2019). Effect of size and concentration of PLGA-PEG nanoparticles on activation and aggregation of washed human platelets. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11100514"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1097\/00008505-200110000-00002","article-title":"Platelet-rich plasma (PRP): What is PRP and what is not PRP?","volume":"10","author":"Marx","year":"2001","journal-title":"Implant Dent."},{"key":"ref_11","first-page":"1","article-title":"Platelet-rich plasma: Support for its use in wound healing","volume":"83","author":"Lacci","year":"2010","journal-title":"Yale J. Biol. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/sj.bjp.0703046","article-title":"ADP can induce aggregation of human platelets via both P2Y1 and P2T receptors","volume":"129","author":"Jarvis","year":"2000","journal-title":"Br. J. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1038\/35051599","article-title":"Identification of the platelet ADP receptor targeted by antithrombotic drugs","volume":"409","author":"Hollopeter","year":"2001","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1309\/Y9EC63RW3XG1V313","article-title":"Platelet Aggregation Testing in Platelet-Rich Plasma Description of Procedures with the Aim to Develop Standards in the Field","volume":"123","author":"Zhou","year":"2005","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1161\/hc0402.104118","article-title":"Passage of inhaled particles into the blood circulation in humans","volume":"105","author":"Nemmar","year":"2002","journal-title":"Circulation"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1038\/nbt994","article-title":"In vivo cancer targeting and imaging with semiconductor quantum dots","volume":"22","author":"Gao","year":"2004","journal-title":"Nat. Biotechnol."},{"key":"ref_17","first-page":"2723","article-title":"CdTe quantum dots induce activation of human platelets: Implications for nanoparticle hemocompatibility","volume":"10","author":"Samuel","year":"2015","journal-title":"Int. J. Nanomed."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1021\/mp800032f","article-title":"Preclinical studies to understand nanoparticle interaction with the immune system and its potential effects on nanoparticle biodistribution","volume":"5","author":"Dobrovolskaia","year":"2008","journal-title":"Mol. Pharm."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1021\/nn900277t","article-title":"Characterization of Antiplatelet Properties of Silver Nanoparticles","volume":"3","author":"Shrivastava","year":"2009","journal-title":"ACS Nano"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1038\/nnano.2008.30","article-title":"Nanoparticle-mediated cellular response is size-dependent","volume":"3","author":"Jiang","year":"2008","journal-title":"Nat. Nanotechnol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/0142-9612(89)90101-4","article-title":"Platelet aggregation induced by latex particles. I. Effects of size, surface potential and hydrophobicity of particles","volume":"10","author":"Miyamoto","year":"1989","journal-title":"Biomaterials"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"14265","DOI":"10.1073\/pnas.0805135105","article-title":"Nanoparticle size and surface properties determine the protein corona with possible implications for biological impacts","volume":"105","author":"Lundqvist","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5087","DOI":"10.1182\/blood-2006-12-027698","article-title":"The growing complexity of platelet aggregation","volume":"109","author":"Jackson","year":"2007","journal-title":"Blood"},{"key":"ref_24","first-page":"631","article-title":"Amorphous silica nanoparticles aggregate human platelets: Potential implications for vascular homeostasis","volume":"7","author":"Corbalan","year":"2012","journal-title":"Int. J. Nanomed."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Lundqvist, M., Augustsson, C., Lilja, M., Lundkvist, K., Dahlb\u00e4ck, B., Linse, S., and Cedervall, T. (2017). The nanoparticle protein corona formed in human blood or human blood fractions. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0175871"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1038\/nnano.2013.181","article-title":"Rapid formation of plasma protein corona critically affects nanoparticle pathophysiology","volume":"8","author":"Tenzer","year":"2013","journal-title":"Nat. Nanotechnol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"312","DOI":"10.3109\/09687688.2010.522117","article-title":"Dynamic and cellular interactions of nanoparticles in vascular-targeted drug delivery (review)","volume":"27","author":"Huang","year":"2010","journal-title":"Mol. Membr. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.tox.2009.01.015","article-title":"The role of nanoparticle size in hemocompatibility","volume":"258","author":"Mayer","year":"2009","journal-title":"Toxicology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1080\/09537100400007390","article-title":"Platelets are covercytes, not phagocytes: Uptake of bacteria involves channels of the open canalicular system","volume":"16","author":"White","year":"2005","journal-title":"Platelets"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.nano.2011.01.007","article-title":"Multistability in platelets and their response to gold nanoparticles","volume":"7","author":"Deb","year":"2011","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4021","DOI":"10.1182\/blood-2001-12-0191","article-title":"Host defense role of platelets: Engulfment of HIV and Staphylococcus aureus occurs in a specific subcellular compartment and is enhanced by platelet activation","volume":"99","author":"Youssefian","year":"2002","journal-title":"Blood"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"383","DOI":"10.3109\/09537104.2012.703792","article-title":"Platelet-adenovirus vs. inert particles interaction: Effect on aggregation and the role of platelet membrane receptors","volume":"24","author":"Gupalo","year":"2013","journal-title":"Platelets"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/24\/9716\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:47:24Z","timestamp":1760179644000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/24\/9716"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,19]]},"references-count":32,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["ijms21249716"],"URL":"https:\/\/doi.org\/10.3390\/ijms21249716","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,19]]}}}