Thermosensitive Polymeric Nanoparticles for Drug Co-Encapsulation and Breast Cancer Treatment
Despite advances in breast cancer treatment, there remains a need for local management of noninvasive, low-grade ductal carcinoma in situ (DCIS). These focal lesions are well suited for local intraductal treatment. Intraductal administration supported target site drug retention, improved efficacy, a...
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MDPI AG
2024-02-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/16/2/231 |
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| author | Vanessa Franco Carvalho Dartora Julia S. Passos Leticia V. Costa-Lotufo Luciana B. Lopes Alyssa Panitch |
| author_facet | Vanessa Franco Carvalho Dartora Julia S. Passos Leticia V. Costa-Lotufo Luciana B. Lopes Alyssa Panitch |
| author_sort | Vanessa Franco Carvalho Dartora |
| collection | DOAJ |
| description | Despite advances in breast cancer treatment, there remains a need for local management of noninvasive, low-grade ductal carcinoma in situ (DCIS). These focal lesions are well suited for local intraductal treatment. Intraductal administration supported target site drug retention, improved efficacy, and reduced systemic exposure. Here, we used a poly(N-isopropyl acrylamide, pNIPAM) nanoparticle delivery system loaded with cytotoxic piplartine and an MAPKAP Kinase 2 inhibitor (YARA) for this purpose. For tumor environment targeting, a collagen-binding peptide SILY (RRANAALKAGELYKSILYGSG-hydrazide) was attached to pNIPAM nanoparticles, and the nanoparticle diameter, zeta potential, drug loading, and release were assessed. The system was evaluated for cytotoxicity in a 2D cell culture and 3D spheroids. In vivo efficacy was evaluated using a chemical carcinogenesis model in female Sprague–Dawley rats. Nanoparticle delivery significantly reduced the IC<sub>50</sub> of piplartine (4.9 times) compared to the drug in solution. The combination of piplartine and YARA in nanoparticles further reduced the piplartine IC<sub>50</sub> (~15 times). Treatment with these nanoparticles decreased the in vivo tumor incidence (5.2 times). Notably, the concentration of piplartine in mammary glands treated with nanoparticles (35.3 ± 22.4 μg/mL) was substantially higher than in plasma (0.7 ± 0.05 μg/mL), demonstrating targeted drug retention. These results indicate that our nanocarrier system effectively reduced tumor development with low systemic exposure. |
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| format | Article |
| id | doaj.art-d8614311b16346c0b624f3fd6b810dc3 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-07T22:18:20Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-d8614311b16346c0b624f3fd6b810dc32024-02-23T15:31:10ZengMDPI AGPharmaceutics1999-49232024-02-0116223110.3390/pharmaceutics16020231Thermosensitive Polymeric Nanoparticles for Drug Co-Encapsulation and Breast Cancer TreatmentVanessa Franco Carvalho Dartora0Julia S. Passos1Leticia V. Costa-Lotufo2Luciana B. Lopes3Alyssa Panitch4Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo 05508-900, BrazilDepartment of Pharmacology, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo 05508-900, BrazilDepartment of Pharmacology, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo 05508-900, BrazilDepartment of Pharmacology, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo 05508-900, BrazilDepartment of Biomedical Engineering, College of Engineering, University of California Davis, Davis, CA 95616, USADespite advances in breast cancer treatment, there remains a need for local management of noninvasive, low-grade ductal carcinoma in situ (DCIS). These focal lesions are well suited for local intraductal treatment. Intraductal administration supported target site drug retention, improved efficacy, and reduced systemic exposure. Here, we used a poly(N-isopropyl acrylamide, pNIPAM) nanoparticle delivery system loaded with cytotoxic piplartine and an MAPKAP Kinase 2 inhibitor (YARA) for this purpose. For tumor environment targeting, a collagen-binding peptide SILY (RRANAALKAGELYKSILYGSG-hydrazide) was attached to pNIPAM nanoparticles, and the nanoparticle diameter, zeta potential, drug loading, and release were assessed. The system was evaluated for cytotoxicity in a 2D cell culture and 3D spheroids. In vivo efficacy was evaluated using a chemical carcinogenesis model in female Sprague–Dawley rats. Nanoparticle delivery significantly reduced the IC<sub>50</sub> of piplartine (4.9 times) compared to the drug in solution. The combination of piplartine and YARA in nanoparticles further reduced the piplartine IC<sub>50</sub> (~15 times). Treatment with these nanoparticles decreased the in vivo tumor incidence (5.2 times). Notably, the concentration of piplartine in mammary glands treated with nanoparticles (35.3 ± 22.4 μg/mL) was substantially higher than in plasma (0.7 ± 0.05 μg/mL), demonstrating targeted drug retention. These results indicate that our nanocarrier system effectively reduced tumor development with low systemic exposure.https://www.mdpi.com/1999-4923/16/2/231ductal carcinoma in situintraductal administrationpiplartinepiperlonguminePNIPAmnanoparticle |
| spellingShingle | Vanessa Franco Carvalho Dartora Julia S. Passos Leticia V. Costa-Lotufo Luciana B. Lopes Alyssa Panitch Thermosensitive Polymeric Nanoparticles for Drug Co-Encapsulation and Breast Cancer Treatment Pharmaceutics ductal carcinoma in situ intraductal administration piplartine piperlongumine PNIPAm nanoparticle |
| title | Thermosensitive Polymeric Nanoparticles for Drug Co-Encapsulation and Breast Cancer Treatment |
| title_full | Thermosensitive Polymeric Nanoparticles for Drug Co-Encapsulation and Breast Cancer Treatment |
| title_fullStr | Thermosensitive Polymeric Nanoparticles for Drug Co-Encapsulation and Breast Cancer Treatment |
| title_full_unstemmed | Thermosensitive Polymeric Nanoparticles for Drug Co-Encapsulation and Breast Cancer Treatment |
| title_short | Thermosensitive Polymeric Nanoparticles for Drug Co-Encapsulation and Breast Cancer Treatment |
| title_sort | thermosensitive polymeric nanoparticles for drug co encapsulation and breast cancer treatment |
| topic | ductal carcinoma in situ intraductal administration piplartine piperlongumine PNIPAm nanoparticle |
| url | https://www.mdpi.com/1999-4923/16/2/231 |
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