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Among the most promising biopolymers is poly(lactic acid) (PLA), with a reported high degree of biocompatibility and biodegradability. In this work, PLA NPs were synthesized according to a controlled gelation process using a combination of single-emulsion and nanoprecipitation methods. This study evaluated the influence of several experimental parameters for accurate control of the PLA NPs\u2019 size distribution and aggregation. Tip sonication (as the stirring method), a PLA concentration of 10 mg\/mL, a PVA concentration of 2.5 mg\/mL, and low-molecular-weight PLA (Mw = 5000) were established as the best experimental conditions to obtain monodisperse PLA NPs. After gelification process optimization, flutamide (FLU) was used as a model drug to evaluate the encapsulation capability of the PLA NPs. The results showed an encapsulation efficiency of 44% for this cytostatic compound. Furthermore, preliminary cell viability tests showed that the FLU@PLA NPs allowed cell viabilities above 90% up to a concentration of 20 mg\/L. The comprehensive findings showcase that the PLA NPs fabricated using this straightforward gelification method hold promise for encapsulating cytostatic compounds, offering a novel avenue for precise drug delivery in cancer therapy.<\/jats:p>","DOI":"10.3390\/gels10040274","type":"journal-article","created":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T10:30:52Z","timestamp":1713436252000},"page":"274","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Optimized Synthesis of Poly(Lactic Acid) Nanoparticles for the Encapsulation of Flutamide"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-6068-4385","authenticated-orcid":false,"given":"Duarte","family":"Almeida","sequence":"first","affiliation":[{"name":"TEMA\u2014Centre for Mechanical Technology and Automation, Department of Mechanical Engineering, University of Aveiro, Campus de Santiago, 3810-193 Aveiro, Portugal"},{"name":"Intelligent Systems Associate Laboratory (LASI), 4800-058 Guimar\u00e3es, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4323-0634","authenticated-orcid":false,"given":"Mariana","family":"Dias","sequence":"additional","affiliation":[{"name":"CICECO\u2014Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, Campus de Santiago, 3810-193 Aveiro, Portugal"}]},{"given":"Beatriz","family":"Teixeira","sequence":"additional","affiliation":[{"name":"CESAM\u2014Centre for Environmental and Marine Studies, Department of Biology, University of Aveiro, Campus de Santiago, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9485-141X","authenticated-orcid":false,"given":"Carolina","family":"Fraz\u00e3o","sequence":"additional","affiliation":[{"name":"CESAM\u2014Centre for Environmental and Marine Studies, Department of Biology, University of Aveiro, Campus de Santiago, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5734-4021","authenticated-orcid":false,"given":"M\u00f3nica","family":"Almeida","sequence":"additional","affiliation":[{"name":"CESAM\u2014Centre for Environmental and Marine Studies, Department of Biology, University of Aveiro, Campus de Santiago, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2302-9661","authenticated-orcid":false,"given":"Gil","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"TEMA\u2014Centre for Mechanical Technology and Automation, Department of Mechanical Engineering, University of Aveiro, Campus de Santiago, 3810-193 Aveiro, Portugal"},{"name":"Intelligent Systems Associate Laboratory (LASI), 4800-058 Guimar\u00e3es, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5404-7718","authenticated-orcid":false,"given":"Miguel","family":"Oliveira","sequence":"additional","affiliation":[{"name":"CESAM\u2014Centre for Environmental and Marine Studies, Department of Biology, University of Aveiro, Campus de Santiago, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5600-2396","authenticated-orcid":false,"given":"Ricardo J. 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