{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T11:12:03Z","timestamp":1790248323012,"version":"4.1.0"},"reference-count":34,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2019,12,6]],"date-time":"2019-12-06T00:00:00Z","timestamp":1575590400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009882","name":"Regione Lombardia","doi-asserted-by":"publisher","award":["Direzione Generale Ricerca, Innovazione, Universit\u00e0, Export e Internazionalizzazione"],"award-info":[{"award-number":["Direzione Generale Ricerca, Innovazione, Universit\u00e0, Export e Internazionalizzazione"]}],"id":[{"id":"10.13039\/501100009882","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["Dipartimenti di Eccellenza-2017\u201d to University of Milano Bicocca, Department of Biotechnology and Biosciences,"],"award-info":[{"award-number":["Dipartimenti di Eccellenza-2017\u201d to University of Milano Bicocca, Department of Biotechnology and Biosciences,"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Unimib","award":["Academic Funding"],"award-info":[{"award-number":["Academic Funding"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>One of the goals of the pharmaceutical sciences is the amelioration of targeted drug delivery. In this context, nanocarrier-dependent transportation represents an ideal method for confronting a broad range of human disorders. In this study, we investigated the possibility of improving the selective release of the anti-cancer drug paclitaxel (PTX) in the gastro-intestinal tract by encapsulating it into the biodegradable nanoparticles made by FDA-approved poly(lactic-co-glycolic acid) (PLGA) and coated with polyethylene glycol to improve their stability (PLGA-PEG-NPs). Our study was performed by combining the synthesis and characterization of the nanodrug with in vivo studies of pharmacokinetics after oral administration in mice. Moreover, fluorescent PLGA-nanoparticles (NPs), were tested both in vitro and in vivo to observe their fate and biodistribution. Our study demonstrated that PLGA-NPs: (1) are stable in the gastric tract; (2) can easily penetrate inside carcinoma colon 2 (CaCo2) cells; (3) reduce the PTX absorption from the gastrointestinal tract, further limiting systemic exposure; (4) enable PTX local targeting. At present, the oral administration of biodegradable nanocarriers is limited because of stomach degradation and the sink effect played by the duodenum. Our findings, however, exhibit promising evidence towards our overcoming these limitations for a more specific and safer strategy against gastrointestinal disorders.<\/jats:p>","DOI":"10.3390\/pharmaceutics11120658","type":"journal-article","created":{"date-parts":[[2019,12,6]],"date-time":"2019-12-06T10:41:44Z","timestamp":1575628904000},"page":"658","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Monitoring the Fate of Orally Administered PLGA Nanoformulation for Local Delivery of Therapeutic Drugs"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0329-3841","authenticated-orcid":false,"given":"Lucia","family":"Morelli","sequence":"first","affiliation":[{"name":"NanoBioLab, Dipartimento di Biotecnologie e Bioscienze, Universit\u00e0 di Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6660-0477","authenticated-orcid":false,"given":"Sara","family":"Gimondi","sequence":"additional","affiliation":[{"name":"IRCCS Mario Negri Institute for Pharmacological Research; Via Mario Negri 2, 20157 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Sevieri","sequence":"additional","affiliation":[{"name":"IRCCS Mario Negri Institute for Pharmacological Research; Via Mario Negri 2, 20157 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Salvioni","sequence":"additional","affiliation":[{"name":"NanoBioLab, Dipartimento di Biotecnologie e Bioscienze, Universit\u00e0 di Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Guizzetti","sequence":"additional","affiliation":[{"name":"NanoBioLab, Dipartimento di Biotecnologie e Bioscienze, Universit\u00e0 di Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Colzani","sequence":"additional","affiliation":[{"name":"NanoBioLab, Dipartimento di Biotecnologie e Bioscienze, Universit\u00e0 di Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Palugan","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Farmaceutiche, Universit\u00e0 di Milano, Via Giuseppe Colombo 71, 20133 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Foppoli","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Farmaceutiche, Universit\u00e0 di Milano, Via Giuseppe Colombo 71, 20133 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Talamini","sequence":"additional","affiliation":[{"name":"IRCCS Mario Negri Institute for Pharmacological Research; Via Mario Negri 2, 20157 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lavinia","family":"Morosi","sequence":"additional","affiliation":[{"name":"IRCCS Mario Negri Institute for Pharmacological Research; Via Mario Negri 2, 20157 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5427-052X","authenticated-orcid":false,"given":"Massimo","family":"Zucchetti","sequence":"additional","affiliation":[{"name":"IRCCS Mario Negri Institute for Pharmacological Research; Via Mario Negri 2, 20157 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina Bruna","family":"Violatto","sequence":"additional","affiliation":[{"name":"IRCCS Mario Negri Institute for Pharmacological Research; Via Mario Negri 2, 20157 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Russo","sequence":"additional","affiliation":[{"name":"IRCCS Mario Negri Institute for Pharmacological Research; Via Mario Negri 2, 20157 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Salmona","sequence":"additional","affiliation":[{"name":"IRCCS Mario Negri Institute for Pharmacological Research; Via Mario Negri 2, 20157 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4577-9575","authenticated-orcid":false,"given":"Davide","family":"Prosperi","sequence":"additional","affiliation":[{"name":"NanoBioLab, Dipartimento di Biotecnologie e Bioscienze, Universit\u00e0 di Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy"},{"name":"Nanomedicine Laboratory, ICS Maugeri S.p.A. SB, Via S. Maugeri 10, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3428-5668","authenticated-orcid":false,"given":"Miriam","family":"Colombo","sequence":"additional","affiliation":[{"name":"NanoBioLab, Dipartimento di Biotecnologie e Bioscienze, Universit\u00e0 di Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Bigini","sequence":"additional","affiliation":[{"name":"IRCCS Mario Negri Institute for Pharmacological Research; Via Mario Negri 2, 20157 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1038\/nnano.2007.387","article-title":"Nanocarriers as an emerging platform for cancer therapy","volume":"2","author":"Peer","year":"2007","journal-title":"Nat. Nanotechnol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"14436","DOI":"10.1073\/pnas.1515202112","article-title":"Nanotechnologies for biomedical science and translational medicine","volume":"112","author":"Heath","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4410","DOI":"10.1021\/acsnano.8b09655","article-title":"Dexamethasone Conjugation to Biodegradable Avidin-Nucleic-Acid-Nano-Assemblies Promotes Selective Liver Targeting and Improves Therapeutic Efficacy in an Autoimmune Hepatitis Murine Model","volume":"13","author":"Violatto","year":"2019","journal-title":"ACS Nano"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.biomaterials.2014.10.030","article-title":"Fluorescent cell-traceable dexamethasone-loaded liposomes for the treatment of inflammatory liver diseases","volume":"37","author":"Bartneck","year":"2015","journal-title":"Biomaterials"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"673","DOI":"10.2217\/nnm.16.5","article-title":"The effect of nanoparticle size on in vivo pharmacokinetics and cellular interaction","volume":"11","author":"Hoshyar","year":"2016","journal-title":"Nanomedicine"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1200\/JCO.1995.13.7.1777","article-title":"Liposomal doxorubicin: Antitumor activity and unique toxicities during two complementary phase I studies","volume":"13","author":"Uziely","year":"1995","journal-title":"J. Clin. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"413","DOI":"10.2174\/0929867043455909","article-title":"Nanoparticles of Biodegradable Polymers for Clinical Administration of Paclitaxel","volume":"11","author":"Feng","year":"2004","journal-title":"Curr. Med. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.ijpharm.2017.11.048","article-title":"Liposomes encapsulating native and cyclodextrin enclosed paclitaxel: Enhanced loading efficiency and its pharmacokinetic evaluation","volume":"536","author":"Bhatt","year":"2018","journal-title":"Int. J. Pharm."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Venugopal, V., Krishnan, S., Palanimuthu, V.R., Sankarankutty, S., Kalaimani, J.K., Karupiah, S., Kit, N.S., and Hock, T.T. (2018). Anti-EGFR anchored paclitaxel loaded PLGA nanoparticles for the treatment of triple negative breast cancer.In-vitro and in-vivo anticancer activities. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0206109"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2602","DOI":"10.1021\/acs.chemrev.5b00346","article-title":"Degradable controlled-release polymers and polymeric nanoparticles: Mechanisms of controlling drug release","volume":"116","author":"Kamaly","year":"2016","journal-title":"Chem. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"957","DOI":"10.2147\/IJN.S152742","article-title":"Investigation of antitumor activities of trastuzumab delivered by PLGA nanoparticles","volume":"13","author":"Colzani","year":"2018","journal-title":"Int. J. Nanomed."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/j.nano.2009.02.002","article-title":"PEGylated PLGA nanoparticles for the improved delivery of doxorubicin","volume":"5","author":"Park","year":"2009","journal-title":"Nanomedicine"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"728","DOI":"10.2174\/0929867324666161205130416","article-title":"Current Strategies in the Modification of PLGA-based Gene Delivery System","volume":"24","author":"Ramezani","year":"2017","journal-title":"Curr. Med. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1515\/ntrev-2012-0084","article-title":"PLA\/PLGA nanoparticles for delivery of drugs across the blood-brain barrier","volume":"2","author":"Li","year":"2013","journal-title":"Nanotechnol. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1016\/j.addr.2013.01.003","article-title":"In vitro and in vivo models for the study of oral delivery of nanoparticles","volume":"65","author":"Gamboa","year":"2013","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.jconrel.2012.01.043","article-title":"PLGA-based nanoparticles: An overview of biomedical applications","volume":"161","author":"Danhier","year":"2012","journal-title":"J. Control. Release"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.apsb.2018.01.013","article-title":"Designing the new generation of intelligent biocompatible carriers for protein and peptide delivery","volume":"8","author":"Wagner","year":"2018","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Santini, B., Zanoni, I., Marzi, R., Cigni, C., Bedoni, M., Gramatica, F., Palugan, L., Corsi, F., Granucci, F., and Colombo, M. (2015). Cream formulation impact on topical administration of engineered colloidal nanoparticles. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0126366"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s12951-017-0249-6","article-title":"Impact of semi-solid formulations on skin penetration of iron oxide nanoparticles","volume":"15","author":"Musazzi","year":"2017","journal-title":"J. Nanobiotechnol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1615\/CritRevTherDrugCarrierSyst.2017018693","article-title":"Lipid Nanoparticles for Nasal\/Intranasal Drug Delivery","volume":"34","author":"Cunha","year":"2017","journal-title":"Crit Rev. Ther. Drug Carr. Syst."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.jconrel.2019.08.015","article-title":"Imatinib-loaded gold nanoparticles inhibit proliferation of fibroblasts and macrophages from systemic sclerosis patients and ameliorate experimental bleomycin-induced lung fibrosis","volume":"310","author":"Codullo","year":"2019","journal-title":"J. Control. Release"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.phrs.2016.05.016","article-title":"Oral delivery of insulin via polyethylene imine-based nanoparticles for colonic release allows glycemic control in diabetic rats","volume":"110","author":"Salvioni","year":"2016","journal-title":"Pharmacol. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.addr.2015.09.012","article-title":"PEGylation as a strategy for improving nanoparticle-based drug and gene delivery","volume":"99","author":"Suk","year":"2016","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.ejpb.2014.12.021","article-title":"In vivo study of the mucus-permeating properties of PEG-coated nanoparticles following oral administration","volume":"97","author":"Inchaurraga","year":"2015","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/s12645-013-0046-3","article-title":"Gemcitabine-loaded PLGA-PEG immunonanoparticles for targeted chemotherapy of pancreatic cancer","volume":"4","author":"Aggarwal","year":"2013","journal-title":"Cancer Nanotechnol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1007\/s11051-012-0920-7","article-title":"Colloidal stability of polymeric nanoparticles in biological fluids","volume":"14","author":"Lazzari","year":"2012","journal-title":"J. Nanopart. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1007\/s00280-005-0160-y","article-title":"Clindamycin-paclitaxel pharmacokinetic interaction in ovarian cancer patients","volume":"58","author":"Fruscio","year":"2006","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1021\/nl104117p","article-title":"Potent engineered PLGA nanoparticles by virtue of exceptionally high chemotherapeutic loadings","volume":"11","author":"Enlow","year":"2011","journal-title":"Nano Lett."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1021\/mp500817h","article-title":"Release Kinetics Study of Poorly Water-Soluble Drugs from Nanoparticles: Are We Doing It Right?","volume":"12","author":"Abouelmagd","year":"2015","journal-title":"Mol. Pharm."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.jconrel.2012.04.042","article-title":"Beyond the imaging: Limitations of cellular uptake study in the evaluation of nanoparticles","volume":"164","author":"Gullotti","year":"2012","journal-title":"J. Control. Release"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Zhang, W., Shi, K., Shi, J., and He, X. (2016). Use of the fluorescence of rhodamine B for the pH sensing of a glycine solution. Proc. SPIE, 10155.","DOI":"10.1117\/12.2247373"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1800164","DOI":"10.1002\/mabi.201800164","article-title":"Self-Assembling PCL-Based Nanoparticles as PTX Solubility Enhancer Excipients","volume":"18","author":"Morosi","year":"2018","journal-title":"Macromol. Biosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1021\/acs.molpharmaceut.5b00383","article-title":"PEGylated Nanoparticles Obtained through Emulsion Polymerization as Paclitaxel Carriers","volume":"13","author":"Colombo","year":"2016","journal-title":"Mol. Pharm."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Tenuta, T., Monopoli, M., Kim, J., Salvati, A., Dawson, K., Sandin, P., and Lynch, I. (2011). Elution of Labile Fluorescent Dye from Nanoparticles during Biological Use. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0025556"}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/11\/12\/658\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:40:09Z","timestamp":1760190009000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/11\/12\/658"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,6]]},"references-count":34,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["pharmaceutics11120658"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics11120658","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,6]]}}}