Synthesis of Amphiphilic Copolymers of N-Vinyl-2-pyrrolidone and Allyl Glycidyl Ether for Co-Delivery of Doxorubicin and Paclitaxel
Abstract
:1. Introduction
2. Materials and Methods
2.1. Synthesis of an Amphiphilic Copolymer of N-Vinyl-2-pyrrolidone and Allyl Glycidyl Ether
2.2. Investigation of the Adsorption of the Amphiphilic Copolymer of N-Vinyl-2-pyrrolidone and Allyl Glycidyl Ether on the Water/Toluene Interface
2.3. Immobilization of Doxorubicin with an Amphiphilic Copolymer of N-Vinyl-2-pyrrolidone and Allyl Glycidyl Ether
2.4. Incorporation of Paclitaxel into an Amphiphilic Copolymer Containing Covalently Immobilized Doxorubicin
3. Results and Discussion
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 2021, 71, 209–249. [Google Scholar] [CrossRef] [PubMed]
- Ventola, C.L. The nanomedicine revolution: Part 1: Emerging concepts. Pharm. Ther. 2012, 37, 512–525. [Google Scholar] [PubMed]
- Sevastre, A.S.; Horescu, C.; Carina Baloi, S.; Cioc, C.E.; Vatu, B.I.; Tuta, C.; Artene, S.A.; Danciulescu, M.M.; Tudorache, S.; Dricu, A. Benefits of Nanomedicine for Therapeutic Intervention in Malignant Diseases. Coatings 2019, 9, 628. [Google Scholar] [CrossRef] [Green Version]
- Soares, S.; Sousa, J.; Pais, A.; Vitorino, C. Nanomedicine: Principles, Properties, and Regulatory Issues. Front. Chem. 2018, 6, 360. [Google Scholar] [CrossRef]
- Saidi, T.; Fortuin, J.; Douglas, T.S. Nanomedicine for drug delivery in South Africa: A protocol for systematic review. Syst. Rev. 2018, 7, 154. [Google Scholar] [CrossRef]
- Li, J.; Mooney, D. Designing hydrogels for controlled drug delivery. Nat. Rev. Mater. 2016, 1, 16071. [Google Scholar] [CrossRef]
- Chandel, A.K.S.; Kumar, C.U.; Jewrajka, S.K. Effect of Polyethylene Glycol on Properties and Drug Encapsulation–Release Performance of Biodegradable/Cytocompatible Agarose–Polyethylene Glycol–Polycaprolactone Amphiphilic Co-Network Gels. ACS Appl. Mater. Interfaces 2016, 8, 3182. [Google Scholar] [CrossRef]
- Bera, A.; Chandel, A.K.S.; Kumar, C.U.; Jewrajka, S.K. Degradable/cytocompatible and pH responsive amphiphilic conetwork gels based on agarose-graft copolymers and polycaprolactone. J. Mater. Chem. B 2015, 3, 8548. [Google Scholar] [CrossRef]
- Chandel, A.K.S.; Nutan, B.; Raval, I.H.; Jewrajka, S.K. Self-Assembly of Partially Alkylated Dextran-graft-poly[(2-dimethylamino)ethyl methacrylate] Copolymer Facilitating Hydrophobic/Hydrophilic Drug Delivery and Improving Conetwork Hydrogel Properties. Biomacromolecules 2018, 19, 1142. [Google Scholar] [CrossRef]
- Chandel, A.K.S.; Bera, A.; Nutan, B.; Jewrajka, S.K. Reactive compatibilizer mediated precise synthesis and application of stimuli responsive polysaccharides-polycaprolactone amphiphilic co-network gels. Polymer 2016, 99, 470. [Google Scholar] [CrossRef]
- Paroha, S.; Chandel, A.K.S.; Dubey, R.D. Nanosystems for drug delivery of coenzyme Q10. Environ. Chem. Lett. 2018, 16, 71. [Google Scholar] [CrossRef]
- Sung, Y.K.; Kim, S.W. Recent advances in polymeric drug delivery systems. Biomater. Res. 2020, 24, 12. [Google Scholar] [CrossRef] [PubMed]
- Martin, C.; Aibani, N.; Callan, J.F.; Callan, B. Recent advances in amphiphilic polymers for simultaneous delivery of hydrophobic and hydrophilic drugs. Ther. Deliv. 2016, 7, 15. [Google Scholar] [CrossRef]
- Nutan, B.; Chandel, A.K.S.; Jewrajka, S.K. Synthesis and Multi-Responsive Self-Assembly of Cationic Poly(caprolactone)-Poly(ethylene glycol) Multiblock Copolymers. Chemistry 2017, 23, 8166–8170. [Google Scholar] [CrossRef] [PubMed]
- Atanase, L.I.; Desbrieres, J.; Riess, G. Micellization of synthetic and polysaccharides-based graft copolymers in aqueous media. Prog. Polym. Sci. 2017, 73, 32. [Google Scholar] [CrossRef]
- Winninger, J.; Iurea, D.M.; Atanase, L.I.; Salhi, S.; Delaite, C.; Riess, G. Micellization of novel biocompatible thermo-sensitive graft copolymers based on poly(ε-caprolactone), poly(N-vinylcaprolactam) and poly(N-vinylpyrrolidone). Eur. Polym. J. 2019, 119, 74. [Google Scholar] [CrossRef]
- Atanase, L.I.; Winninger, J.; Delaite, C.; Riess, G. Reversible addition–fragmentation chain transfer synthesis and micellar characteristics of biocompatible amphiphilic poly(vinyl acetate)-graft-poly(N-vinyl-2-pyrrolidone) copolymers. Eur. Polym. J. 2014, 53, 109. [Google Scholar] [CrossRef]
- Daraba, O.M.; Cadinoiu, A.N.; Rata, D.M.; Atanase, L.I.; Vochita, G. Antitumoral Drug-Loaded Biocompatible Polymeric Nanoparticles Obtained by Non-Aqueous Emulsion Polymerization. Polymers 2020, 12, 1018. [Google Scholar] [CrossRef]
- Essa, D.; Kondiah, P.P.D.; Choonara, Y.E.; Pillay, V. The Design of Poly(lactide-co-glycolide) Nanocarriers for Medical Applications. Front. Bioeng. Biotechnol. 2020, 8, 48. [Google Scholar] [CrossRef]
- Kulikov, P.P.; Luss, A.L.; Nelemans, L.C.; Shtilman, M.I.; Mezhuev, Y.O.; Kuznetsov, I.A.; Sizova, O.Y.; Christiansen, G.; Pennisi, C.P.; Gurevich, L. Synthesis, self-assembly and in vitro cellular uptake kinetics of nanosized drug carriers based on aggregates of amphiphilic oligomers of N-vinyl-2-pyrrolidone. Materials 2021, 14, 5977. [Google Scholar] [CrossRef]
- Luss, A.L.; Kulikov, P.P.; Romme, S.B.; Andersen, C.L.; Pennisi, C.P.; Docea, A.O.; Kuskov, A.N.; Velonia, K.; Mezhuev, Y.O.; Shtilman, M.I.I.; et al. Nanosized carriers based on amphiphilic poly-N-vinyl-2-pyrrolidone for intranuclear drug delivery. Nanomedicine 2018, 13, 703–715. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kurakula, M.; Rao, G.S.N.K. Pharmaceutical assessment of polyvinylpyrrolidone (PVP): As excipient from conventional to controlled delivery systems with a spotlight on COVID-19 inhibition. J. Drug. Deliv. Sci. Technol. 2020, 60, 102046. [Google Scholar] [CrossRef] [PubMed]
- Tsatsakis, A.; Stratidakis, A.; Goryachaya, A.; Tzatzarakis, M.; Stivaktakis, P.; Docea, A.; Berdiaki, A.; Nikitovic, D.; Velonia, K.; Shtilman, M.; et al. In vitro blood compatibility and in vitro cytotoxicity of amphiphilic poly-N-vinylpyrrolidone nanoparticles. Food Chem. Toxicol. 2019, 127, 42–52. [Google Scholar] [CrossRef] [PubMed]
- Kuskov, A.N.; Luss, A.L.; Gritskova, I.A.; Shtilman, M.I.; Motyakin, M.V.; Levina, I.I.; Nechaeva, A.M.; Sizova, O.Y.; Tsatsakis, A.M.; Mezhuev, Y.O. Kinetics and Mechanism of Synthesis of Carboxyl-Containing N-Vinyl-2-Pyrrolidone Telehelics for Pharmacological Use. Polymers 2021, 13, 2569. [Google Scholar] [CrossRef]
- Bayat Mokhtari, R.; Homayouni, T.S.; Baluch, N.; Morgatskaya, E.; Kumar, S.; Das, B.; Yeger, H. Combination therapy in combating cancer. Oncotarget 2017, 8, 38022–38043. [Google Scholar] [CrossRef] [Green Version]
- Zhao, M.; Ding, X.F.; Shen, J.Y.; Zhang, X.P.; Ding, X.W.; Xu, B. Use of liposomal doxorubicin for adjuvant chemotherapy of breast cancer in clinical practice. J. Zhejiang Univ. Sci. B 2017, 18, 15–26. [Google Scholar] [CrossRef]
- Hong, Y.; Che, S.; Hui, B.; Yang, Y.; Wang, X.; Zhang, X.; Qiang, Y.; Ma, H. Lung cancer therapy using doxorubicin and curcumin combination: Targeted prodrug based, pH sensitive nanomedicine. Biomed Pharmacother. 2019, 112, 108614. [Google Scholar] [CrossRef]
- Zhou, W.; Tan, W.; Huang, X.; Yu, H.G. Doxorubicin combined with Notch1-targeting siRNA for the treatment of gastric cancer. Oncol. Lett. 2018, 16, 2805–2812. [Google Scholar] [CrossRef] [Green Version]
- Savani, M.; Murugan, P.; Skubitz, K.M. Long-term cure of soft tissue sarcoma with pegylated-liposomal doxorubicin after doxorubicin and ifosfamide failure. Clin. Sarcoma Res. 2019, 9, 1. [Google Scholar] [CrossRef]
- Lee, K.W.; Kim, D.Y.; Yun, T.; Kim, D.W.; Kim, T.Y.; Yoon, S.S.; Heo, D.S.; Bang, Y.J.; Park, S.; Kim, B.K.; et al. Doxorubicin-based chemotherapy for diffuse large B-cell lymphoma in elderly patients: Comparison of treatment outcomes between young and elderly patients and the significance of doxorubicin dosage. Cancer 2003, 98, 2651–2656. [Google Scholar] [CrossRef]
- Inoue, S.; Setoyama, Y.; Odaka, A. Doxorubicin treatment induces tumor cell death followed by immunomodulation in a murine neuroblastoma model. Exp. Ther. Med. 2014, 7, 703–708. [Google Scholar] [CrossRef] [Green Version]
- Liao, W.H.; Hsiao, M.Y.; Kung, Y.; Huang, A.P.; Chen, W.S. Investigation of the Therapeutic Effect of Doxorubicin Combined With Focused Shockwave on Glioblastoma. Front. Oncol. 2021, 11, 711088. [Google Scholar] [CrossRef]
- Thorn, C.F.; Oshiro, C.; Marsh, S.; Hernandez-Boussard, T.; McLeod, H.; Klein, T.E.; Altman, R.B. Doxorubicin pathways: Pharmacodynamics and adverse effects. Pharm. Genom. 2011, 21, 440–446. [Google Scholar] [CrossRef]
- Taymaz-Nikerel, H.; Karabekmez, M.E.; Eraslan, S.; Kırdar, B. Doxorubicin induces an extensive transcriptional and metabolic rewiring in yeast cells. Sci. Rep. 2018, 8, 13672. [Google Scholar] [CrossRef] [Green Version]
- Alves, A.C.; Magarkar, A.; Horta, M.; Lima, J.L.F.C.; Bunker, A.; Nunes, C.; Reis, S. Influence of doxorubicin on model cell membrane properties: Insights from in vitro and in silico studies. Sci. Rep. 2017, 7, 6343. [Google Scholar] [CrossRef] [Green Version]
- Chatterjee, K.; Zhang, J.; Honbo, N.; Karliner, J.S. Doxorubicin cardiomyopathy. Cardiology 2010, 115, 155–162. [Google Scholar] [CrossRef]
- Zhao, L.; Zhang, B. Doxorubicin induces cardiotoxicity through upregulation of death receptors mediated apoptosis in cardiomyocytes. Sci. Rep. 2017, 7, 44735. [Google Scholar] [CrossRef] [Green Version]
- Rawat, P.S.; Jaiswa, l.A.; Khurana, A.; Bhatti, J.S.; Navik, U. Doxorubicin-induced cardiotoxicity: An update on the molecular mechanism and novel therapeutic strategies for effective management. Biomed. Pharmacother. 2021, 139, 111708. [Google Scholar] [CrossRef]
- Prados, J.; Melguizo, C.; Ortiz, R.; Vélez, C.; Alvarez, P.J.; Arias, J.L.; Ruíz, M.A.; Gallardo, V.; Aranega, A. Doxorubicin-loaded nanoparticles: New advances in breast cancer therapy. Anticancer. Agents Med. Chem. 2012, 12, 1058–1070. [Google Scholar] [CrossRef]
- Feng, S.N.; Zhan, H.J.; Zhi, C.Y.; Gao, X.D.; Nakanishi, H. pH-responsive charge-reversal polymer-functionalized boron nitride nanospheres for intracellular doxorubicin delivery. Int. J. Nanomed. 2018, 13, 641–652. [Google Scholar] [CrossRef] [Green Version]
- Li, L.; Zou, T.; Liang, M.; Mezhuev, Y.; Tsatsakis, A.M.; Dordevic, A.B.; Lan, M.; Liu, F.; Cai, T.; Gong, P.; et al. Screening of metabolites in the treatment of liver cancer xenografts HepG2/ADR by psoralen-loaded lipid nanoparticles. Eur. J. Pharm. Biopharm. 2021, 165, 337–344. [Google Scholar] [CrossRef] [PubMed]
- Susa, M.; Iyer, A.K.; Ryu, K.; Hornicek, F.J.; Mankin, H.; Amiji, M.M.; Duan, Z. Doxorubicin loaded polymeric nanoparticulate delivery system to overcome drug resistance in osteosarcoma. BMC Cancer 2009, 9, 399. [Google Scholar] [CrossRef] [PubMed]
- Pieper, S.; Langer, K. Doxorubicin-loaded PLGA nanoparticles-a systematic evaluation of preparation techniques and parameters. Mater. Today Proc. 2017, 4, 188–192. [Google Scholar] [CrossRef]
- Cui, J.; Yan, Y.; Such, G.K.; Liang, K.; Ochs, C.J.; Postma, A.; Caruso, F. Immobilization and intracellular delivery of an anticancer drug using mussel-inspired polydopamine capsules. Biomacromolecules 2012, 13, 2225–2228. [Google Scholar] [CrossRef] [PubMed]
- Norouzi, M.; Yathindranath, V.; Thliveris, J.A.; Kopec, B.M.; Siahaan, T.J.; Miller, D.W. Doxorubicin-loaded iron oxide nanoparticles for glioblastoma therapy: A combinational approach for enhanced delivery of nanoparticles. Sci. Rep. 2020, 10, 11292. [Google Scholar] [CrossRef]
- Du, Y.; Xia, L.; Jo, A.; Davis, R.M.; Bissel, P.; Ehrich, M.F.; Kingston, D.G.I. Synthesis and Evaluation of Doxorubicin-Loaded Gold Nanoparticles for Tumor-Targeted Drug Delivery. Bioconjug. Chem. 2018, 29, 420–430. [Google Scholar] [CrossRef]
- Jiang, H.; Liang, G.; Dai, M.; Dong, Y.; Wu, Y.; Zhang, L.; Xi, Q.; Qi, L. Preparation of doxorubicin-loaded collagen-PAPBA nanoparticles and their anticancer efficacy in ovarian cancer. Ann. Transl. Med. 2020, 8, 880. [Google Scholar] [CrossRef]
- Rahman, A.M.; Yusuf, S.W.; Ewer, M.S. Anthracycline-induced cardiotoxicity and the cardiac-sparing effect of liposomal formulation. Int. J. Nanomed. 2007, 2, 567–583. [Google Scholar]
- Cui, Y.; Xu, Q.; Chow, P.K.; Wang, D.; Wang, C.H. Transferrin-conjugated magnetic silica PLGA nanoparticles loaded with doxorubicin and paclitaxel for brain glioma treatment. Biomaterials 2013, 34, 8511–8520. [Google Scholar] [CrossRef]
- Dong, X.; Mattingly, C.A.; Tseng, M.T.; Cho, M.J.; Liu, Y.; Adams, V.R.; Mumper, R.J. Doxorubicin and paclitaxel-loaded lipid-based nanoparticles overcome multidrug resistance by inhibiting P-glycoprotein and depleting ATP. Cancer Res. 2009, 69, 3918–3926. [Google Scholar] [CrossRef] [Green Version]
- Li, Y.; Hou, H.; Zhang, P.; Zhang, Z. Co-delivery of doxorubicin and paclitaxel by reduction/pH dual responsive nanocarriers for osteosarcoma therapy. Drug Deliv. 2020, 27, 1044–1053. [Google Scholar] [CrossRef] [PubMed]
- Marupudi, N.I.; Han, J.E.; Li, K.W.; Renard, V.M.; Tyler, B.M.; Brem, H. Paclitaxel: A review of adverse toxicities and novel delivery strategies. Expert Opin. Drug Saf. 2007, 6, 609–621. [Google Scholar] [CrossRef] [PubMed]
- Pigareva, V.A.; Alekhina, Y.A.; Grozdova, I.D.; Zhu, X.; Spiridonov, V.V. Magneto-sensitive and enzymatic hydrolysis-resistant systems for the targeted delivery of paclitaxel based on polylactide micelles with an external polyethylene oxide corona. Polym. Int. 2022, 71, 456–463. [Google Scholar] [CrossRef]
- Kulikov, P.P.; Kuskov, A.N.; Goryachaya, A.V.; Luss, A.L.; Shtilman, M.I. Amphiphilic poly-N-vinyl-2-pyrrolidone: Synthesis, properties, nanoparticles. Polym. Sci. Ser. D 2017, 10, 263–268. [Google Scholar] [CrossRef]
- Diniz, T.M.F.F.; Tavares, M.I.B. NMR study of poly(vinylpyrrolidone)/poly(ethylene oxide) blends. J. Appl. Polym. Sci. 2002, 85, 2820–2823. [Google Scholar] [CrossRef]
- Zhang, X.; Takegoshi, K.; Hikichi, K. High-resolution solid-state 13C nuclear magnetic resonance study on poly(vinyl alcohol)/poly(vinylpyrrolidone) blends. Polymer 1992, 33, 712–717. [Google Scholar] [CrossRef]
- Silverstein, R.M.; Webster, F.X.; Kiemle, D.J. Spectrometric Identification of Organic Compounds, 7th ed.; John Wiley & Sons, Inc.: New York, NY, USA, 2005. [Google Scholar]
- Matsumoto, A.; Kumagai, T.; Aota, H.; Kawasaki, H.; Arakawa, R. Reassessment of free-radical polymerization mechanism of allyl acetate based on end-group determination of resulting oligomers by MALDI-TOF-MS spectrometry. Polym. J. 2009, 41, 26–33. [Google Scholar] [CrossRef] [Green Version]
- Nguyen, T.N.; Nguyen, T.T.; Nghiem, T.H.L.; Nguyen, D.T.; Tran, T.T.H.; Vu, D.; Nguyen, T.B.N.; Nguyen, T.M.H.; Nguyen, V.T.; Nguyen, M.H. Optical properties of doxorubicin hydrochloride load and release on silica nanoparticle platform. Molecules 2021, 26, 3968. [Google Scholar] [CrossRef]
- Mezhuev, Y.O.; Varankin, A.V.; Luss, A.L.; Dyatlov, V.A.; Tsatsakis, A.M.; Shtilman, M.I.; Korshak, Y.V. Immobilization of dopamine on the copolymer of N-vinyl-2-pyrrolidone and allyl glycidyl ether and synthesis of new hydrogels. Polym. Int. 2020, 69, 1275–1282. [Google Scholar] [CrossRef]
- O’Neil, J.; Heckelman, P.E.; Koch, C.B.; Roman, K.J. The Merck Index—An Encyclopedia of Chemicals, Drugs, and Biologicals; Merck Co., Inc.: Whitehouse Station, NJ, USA, 2006; p. 1204. [Google Scholar]
- Lee, J.S.; Oh, H.; Sung, D.; Lee, J.H.; Choi, W.I. High Solubilization and controlled release of paclitaxel using thermosponge nanoparticles for effective cancer therapy. Pharmaceutics 2021, 13, 1150. [Google Scholar] [CrossRef]
- England, C.G.; Miller, M.C.; Kuttan, A.; Trent, J.O.; Frieboes, H.B. Release kinetics of paclitaxel and cisplatin from two and three layered gold nanoparticles. Eur. J. Pharm. Biopharm. 2015, 92, 120–129. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shi, K.; Jiang, Y.; Zhang, M.; Wang, Y.; Cui, F. Tocopheryl succinate-based lipid nanospheres for paclitaxel delivery: Preparation, characters, and in vitro release kinetics. Drug Deliv. 2010, 17, 1–10. [Google Scholar] [CrossRef] [PubMed]
VP/AGE | Гmax × 10−7 mol·m−2 | S0 × 1018, m2 | δ × 109, m | CAC, mol·m−3 | |
---|---|---|---|---|---|
9 | 6700 | 7.1 | 2.34 | 4.32 | 0.0057 |
4.5 | 2430 | 7.99 | 2.08 | 1.74 | 0.0157 |
3 | 1850 | 16.5 | 1.01 | 2.7 | 0.0285 |
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Nechaeva, A.; Artyukhov, A.; Luss, A.; Shtilman, M.; Gritskova, I.; Shulgin, A.; Motyakin, M.; Levina, I.; Krivoborodov, E.; Toropygin, I.; et al. Synthesis of Amphiphilic Copolymers of N-Vinyl-2-pyrrolidone and Allyl Glycidyl Ether for Co-Delivery of Doxorubicin and Paclitaxel. Polymers 2022, 14, 1727. https://doi.org/10.3390/polym14091727
Nechaeva A, Artyukhov A, Luss A, Shtilman M, Gritskova I, Shulgin A, Motyakin M, Levina I, Krivoborodov E, Toropygin I, et al. Synthesis of Amphiphilic Copolymers of N-Vinyl-2-pyrrolidone and Allyl Glycidyl Ether for Co-Delivery of Doxorubicin and Paclitaxel. Polymers. 2022; 14(9):1727. https://doi.org/10.3390/polym14091727
Chicago/Turabian StyleNechaeva, Anna, Alexander Artyukhov, Anna Luss, Mikhail Shtilman, Inessa Gritskova, Anton Shulgin, Mikhail Motyakin, Irina Levina, Efrem Krivoborodov, Ilya Toropygin, and et al. 2022. "Synthesis of Amphiphilic Copolymers of N-Vinyl-2-pyrrolidone and Allyl Glycidyl Ether for Co-Delivery of Doxorubicin and Paclitaxel" Polymers 14, no. 9: 1727. https://doi.org/10.3390/polym14091727