Self-Assembled Nanoparticles Based on Block-Copolymers of Poly(2-Deoxy-2-methacrylamido-d-glucose)/Poly(N-Vinyl Succinamic Acid) with Poly(O-Cholesteryl Methacrylate) for Delivery of Hydrophobic Drugs
Abstract
:1. Introduction
2. Results and Discussion
2.1. Synthesis of PMAG-b-PChMA
2.2. Synthesis of PVSAA-b-PChMA-b-PVSAA
2.3. Thermal Properties of Synthesized Block-Copolymers
2.4. Preparation and Characterization of Polymer Nanoparticles
2.5. Cytotoxicity and Uptake by Macrophages
2.6. Paclitaxel Delivery Systems
3. Materials and Methods
3.1. Materials
3.2. Instruments for Polymer Characterization
3.3. Methods
3.3.1. Synthesis and Characterization of PMAG-b-PChMA
3.3.2. Synthesis of PVSI-b-PChMA-b-PVSI
3.3.3. Preparation of PVSAA-b-PChMA-b-PVSAA
3.3.4. Preparation and Characterization of Nanoparticles
3.3.5. Encapsulation of Paclitaxel
3.3.6. Uptake by Macrophages
3.3.7. Cytotoxicity Study
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Perin, F.; Motta, A.; Maniglio, D. Amphiphilic copolymers in biomedical applications: Synthesis routes and property control. Mater. Sci. Eng. C 2021, 123, 111952. [Google Scholar] [CrossRef]
- Agrahari, V.; Agrahari, V. Advances and applications of block-copolymer-based nanoformulations. Drug Discov. Today 2018, 23, 1139–1151. [Google Scholar] [CrossRef] [PubMed]
- Bodratti, A.M.; Alexandridis, P. Amphiphilic block copolymers in drug delivery: Advances in formulation structure and performance. Expert Opin. Drug Deliv. 2018, 15, 1085–1104. [Google Scholar] [CrossRef]
- Fetsch, C.; Gaitzsch, J.; Messager, L.; Battaglia, G.; Luxenhofer, R. Self-Assembly of Amphiphilic Block Copolypeptoids–Micelles, Worms and Polymersomes. Sci. Rep. 2016, 6, 33491. [Google Scholar] [CrossRef] [Green Version]
- Blanazs, A.; Armes, S.P.; Ryan, A.J. Self-Assembled Block Copolymer Aggregates: From Micelles to Vesicles and their Biological Applications. Macromol. Rapid Commun. 2009, 30, 267–277. [Google Scholar] [CrossRef]
- Yotsumoto, K.; Ishii, K.; Kokubo, M.; Yasuoka, S. Improvement of the skin penetration of hydrophobic drugs by polymeric micelles. Int. J. Pharm. 2018, 553, 132–140. [Google Scholar] [CrossRef]
- Chen, W.; Meng, F.; Cheng, R.; Zhong, Z. Rapidly pH-responsive degradable polymersomes for triggered release of hydrophilic and hydrophobic anticancer drugs. J. Control. Release 2011, 152, e7–e9. [Google Scholar] [CrossRef]
- Zashikhina, N.N.; Volokitina, M.V.; Korzhikov-Vlakh, V.A.; Tarasenko, I.I.; Lavrentieva, A.; Scheper, T.; Rühl, E.; Orlova, R.V.; Tennikova, T.B.; Korzhikova-Vlakh, E.G. Self-assembled polypeptide nanoparticles for intracellular irinotecan delivery. Eur. J. Pharm. Sci. 2017, 109, 1–12. [Google Scholar] [CrossRef] [PubMed]
- Hsu, C.W.; Hsieh, M.H.; Xiao, M.C.; Chou, Y.H.; Wang, T.H.; Chiang, W.H. pH-responsive polymeric micelles self-assembled from benzoic-imine-containing alkyl-modified PEGylated chitosan for delivery of amphiphilic drugs. Int. J. Biol. Macromol. 2020, 163, 1106–1116. [Google Scholar] [CrossRef] [PubMed]
- Sundar, D.S.; Antoniraj, M.G.; Kumar, C.S.; Mohapatra, S.S.; Houreld, N.N.; Ruckmani, K. Recent Trends of Biocompatible and Biodegradable Nanoparticles in Drug Delivery: A Review. Curr. Med. Chem. 2016, 23, 3730–3751. [Google Scholar] [CrossRef] [PubMed]
- Anju, S.; Prajitha, N.; Sukanya, V.S.; Mohanan, P.V. Complicity of degradable polymers in health-care applications. Mater. Today Chem. 2020, 16, 100236. [Google Scholar] [CrossRef]
- Tamariz, E.; Rios-Ramírez, A. Biodegradation of Medical Purpose Polymeric Materials and Their Impact on Biocompatibility. In Biodegradation—Life of Science; Chamy, R., Rosenkranz, F., Eds.; IntechOpen: London, UK, 2013. [Google Scholar]
- Kalidas, V.K.; Pavendhan, R.; Sudhakar, K.; Sumanth, T.P.; Sharvesh Ram, A.; Santhosh Kumar, S.; Yeswanth Kumar, K. Study of synthesis and analysis of bio-inspired polymers-review. Mater. Today Proc. 2021, 44, 3856–3860. [Google Scholar] [CrossRef]
- Elmowafy, E.M.; Tiboni, M.; Soliman, M.E. Biocompatibility, biodegradation and biomedical applications of poly(lactic acid)/poly(lactic-co-glycolic acid) micro and nanoparticles. J. Pharm. Investig. 2019, 49, 347–380. [Google Scholar] [CrossRef]
- Okada, M. Molecular design and syntheses of glycopolymers. Prog. Polym. Sci. 2001, 26, 67–104. [Google Scholar] [CrossRef]
- Morell, M.; Puiggalí, J. Hybrid Block Copolymers Constituted by Peptides and Synthetic Polymers: An Overview of Synthetic Approaches, Supramolecular Behavior and Potential Applications. Polymers 2013, 5, 188–224. [Google Scholar] [CrossRef] [Green Version]
- Levit, M.; Zashikhina, N.; Vdovchenko, A.; Dobrodumov, A.; Zakharova, N.; Kashina, A.; Rühl, E.; Lavrentieva, A.; Scheper, T.; Tennikova, T.; et al. Bio-Inspired Amphiphilic Block-Copolymers Based on Synthetic Glycopolymer and Poly(Amino Acid) as Potential Drug Delivery Systems. Polymers 2020, 12, 183. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, Y.; Wu, F.; Yuan, W.; Jin, T. Polymersomes of asymmetric bilayer membrane formed by phase-guided assembly. J. Control. Release 2010, 147, 413–419. [Google Scholar] [CrossRef]
- Fang, Y.; Jiang, Y.; Zou, Y.; Meng, F.; Zhang, J.; Deng, C.; Sun, H.; Zhong, Z. Targeted glioma chemotherapy by cyclic RGD peptide-functionalized reversibly core-crosslinked multifunctional poly(ethylene glycol)- b -poly(ε-caprolactone) micelles. Acta Biomater. 2017, 50, 396–406. [Google Scholar] [CrossRef]
- Kukula, H.; Schlaad, H.; Antonietti, M.; Förster, S. The formation of polymer vesicles or “peptosomes” by polybutadiene-block-poly(L-glutamate)s in dilute aqueous solution. J. Am. Chem. Soc. 2002, 124, 1658–1663. [Google Scholar] [CrossRef]
- Polyakov, D.; Sinitsyna, E.; Grudinina, N.; Antipchik, M.; Sakhabeev, R.; Korzhikov-vlakh, V.; Shavlovsky, M.; Korzhikova-vlakh, E.; Tennikova, T. Polymer Particles Bearing Recombinant LEL CD81 as Trapping Systems for Hepatitis C Virus. Pharmaceutics 2021, 13, 672. [Google Scholar] [CrossRef]
- Pilipenko, I.; Korzhikov-Vlakh, V.; Valtari, A.; Anufrikov, Y.; Kalinin, S.; Ruponen, M.; Krasavin, M.; Urtti, A.; Tennikova, T. Mucoadhesive properties of nanogels based on stimuli-sensitive glycosaminoglycan-graft-pNIPAAm copolymers. Int. J. Biol. Macromol. 2021, 186, 864–872. [Google Scholar] [CrossRef]
- Minoda, M.; Otsubo, T.; Yamamoto, Y.; Zhao, J.; Honda, Y.; Tanaka, T.; Motoyanagi, J. The First Synthesis of Periodic and Alternating Glycopolymers by RAFT Polymerization: A Novel Synthetic Pathway for Glycosaminoglycan Mimics. Polymers 2019, 11, 70. [Google Scholar] [CrossRef] [Green Version]
- Levit, M.; Zashikhina, N.; Dobrodumov, A.; Kashina, A.; Tarasenko, I.; Panarin, E.; Fiorucci, S.; Korzhikova-Vlakh, E.; Tennikova, T. Synthesis and characterization of well-defined poly(2-deoxy-2-methacrylamido-d-glucose) and its biopotential block copolymers via RAFT and ROP polymerization. Eur. Polym. J. 2018, 105, 26–37. [Google Scholar] [CrossRef]
- Korzhikov, V.; Roeker, S.; Vlakh, E.; Kasper, C.; Tennikova, T. Synthesis of Multifunctional Polyvinylsaccharide Containing Controllable Amounts of Biospecific Ligands. Bioconjug. Chem. 2008, 19, 617–625. [Google Scholar] [CrossRef]
- Blanco, E.; Shen, H.; Ferrari, M. Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat. Biotechnol. 2015, 33, 941–951. [Google Scholar] [CrossRef]
- Sevimli, S.; Inci, F.; Zareie, H.M.; Bulmus, V. Well-Defined Cholesterol Polymers with pH-Controlled Membrane Switching Activity. Biomacromolecules 2012, 13, 3064–3075. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fox, M.E.; Szoka, F.C.; Fréchet, J.M.J. Soluble Polymer Carriers for the Treatment of Cancer: The Importance of Molecular Architecture. Acc. Chem. Res. 2009, 42, 1141. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Vázquez-Dorbatt, V.; Lee, J.; Lin, E.-W.; Maynard, H.D. Synthesis of Glycopolymers by Controlled Radical Polymerization Techniques and Their Applications. ChemBioChem 2012, 13, 2478–2487. [Google Scholar] [CrossRef]
- Chernikova, E.V.; Sivtsov, E. V Reversible Addition-Fragmentation Chain-Transfer Polymerization: Fundamentals and Use in Practice. Polym. Sci. B 2017, 59, 117–146. [Google Scholar] [CrossRef]
- Matyjaszewski, K. Atom Transfer Radical Polymerization (ATRP): Current Status and Future Perspectives. Macromolecules 2012, 45, 4015–4039. [Google Scholar] [CrossRef]
- Barner-Kowollik, C. Handbook of RAFT Polymerization; Wiley-VCH: Weinheim, Germany, 2008. [Google Scholar]
- Moad, G. Mechanism and Kinetics of Dithiobenzoate-Mediated RAFT Polymerization-Status of the Dilemma. Macromol. Chem. Phys. 2014, 215, 9–26. [Google Scholar] [CrossRef]
- Rizzardo, E.; Moad, G.; Thang, S.H. RAFT Polymerization in Bulk Monomer or in (Organic) Solution. In Handbook of RAFT Polymerization; Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim, Germany, 2008; pp. 189–234. [Google Scholar]
- Sun, K.; Xu, M.; Zhou, K.; Nie, H.; Quan, J.; Zhu, L. Thermoresponsive diblock glycopolymer by RAFT polymerization for lectin recognition. Mater. Sci. Eng. C 2016, 68, 172–176. [Google Scholar] [CrossRef] [PubMed]
- Wang, Y.; Ling, J. Synthetic protocols toward polypeptide conjugates via chain end functionalization after RAFT polymerization. RSC Adv. 2015, 5, 18546–18553. [Google Scholar] [CrossRef]
- Zhou, Y.; Briand, V.A.; Sharma, N.; Ahn, S.; Kasi, R.M. Polymers Comprising Cholesterol: Synthesis, Self-Assembly, and Applications. Materials 2009, 2, 636–660. [Google Scholar] [CrossRef]
- Mori, H.; Endo, T. Amino-Acid-Based Block Copolymers by RAFT Polymerization. Macromol. Rapid Commun. 2012, 33, 1090–1107. [Google Scholar] [CrossRef] [PubMed]
- Jennings, J.; Beija, M.; Kennon, J.T.; Willcock, H.; O’Reilly, R.K.; Rimmer, S.; Howdle, S.M. Advantages of Block Copolymer Synthesis by RAFT-Controlled Dispersion Polymerization in Supercritical Carbon Dioxide. Macromolecules 2013, 46, 6843–6851. [Google Scholar] [CrossRef] [Green Version]
- Lowe, A.; Sumerlin, B.; McCormick, C.L. The direct polymerization of 2-methacryloxyethyl glucoside via aqueous reversible addition-fragmentation chain transfer (RAFT) polymerization. Polymer 2003, 44, 6761–6765. [Google Scholar] [CrossRef]
- Pearson, S.; Vitucci, D.; Khine, Y.Y.; Dag, A.; Lu, H.; Save, M.; Billon, L.; Stenzel, M.H. Light-responsive azobenzene-based glycopolymer micelles for targeted drug delivery to melanoma cells. Eur. Polym. J. 2015, 69, 616–627. [Google Scholar] [CrossRef]
- Smith, A.E.; Sizovs, A.; Grandinetti, G.; Xue, L.; Reineke, T.M. Diblock glycopolymers promote colloidal stability of polyplexes and effective pDNA and siRNA delivery under physiological salt and serum conditions. Biomacromolecules 2011, 12, 3015–3022. [Google Scholar] [CrossRef]
- Dai, X.-H.; Wang, Z.-M.; Liu, W.; Dong, C.-M.; Pan, J.-M.; Yuan, S.-S.; Yan, Y.; Liu, D.-M.; Sun, L. Biomimetic star-shaped porphyrin-cored poly(l-lactide)-b-glycopolymer block copolymers for targeted photodynamic therapy. Colloid Polym. Sci. 2014, 9, 2111–2122. [Google Scholar] [CrossRef]
- Takada, K.; Matsumoto, A. Reversible addition-fragmentation chain transfer polymerization of diisopropyl fumarate using various dithiobenzoates as chain transfer agents. J. Polym. Sci. A. 2017, 55, 3266–3275. [Google Scholar] [CrossRef]
- Fu, J.; Cheng, Z.; Zhou, N.; Zhu, J.; Zhang, W.; Zhu, X. Reversible addition-fragmentation chain transfer polymerizations of styrene with two novel trithiocarbonates as RAFT agents. Polymer 2008, 49, 5431–5438. [Google Scholar] [CrossRef]
- Moad, G. A Critical Survey of Dithiocarbamate Reversible Addition-Fragmentation Chain Transfer (RAFT) Agents in Radical Polymerization. J. Polym. Sci. Part A Polym. Chem. 2019, 57, 216–227. [Google Scholar] [CrossRef] [Green Version]
- Huang, C.-F.H.; Yoon, J.A.Y.A.; Matyjaszewski, K.M. Synthesis of N-vinylcarbazole–N-vinylpyrrolidone amphiphilic block copolymers by xanthate-mediated controlled radical polymerization. Can. J. Chem. 2010, 88, 228–235. [Google Scholar] [CrossRef]
- Destarac, M. On the Critical Role of RAFT Agent Design in Reversible Addition-Fragmentation Chain Transfer (RAFT) Polymerization. Polym. Rev. 2011, 51, 163–187. [Google Scholar] [CrossRef]
- Lowe, A.B.; Wang, R. Synthesis of controlled-structure AB diblock copolymers of 3-O-methacryloyl-1,2:3,4-di-O-isopropylidene-d-galactopyranose and 2-(dimethylamino)ethyl methacrylate. Polymer 2007, 48, 2221–2230. [Google Scholar] [CrossRef]
- Keddie, D.J. A guide to the synthesis of block copolymers using reversible-addition fragmentation chain transfer (RAFT) polymerization. Chem. Soc. Rev. 2013, 43, 496–505. [Google Scholar] [CrossRef] [PubMed]
- Cole, K.C.; Thomas, Y.; Pellerin, E.; Dumoulin, M.M.; Paroli, R.M. New Approach to Quantitative Analysis of Two-Component Polymer Systems by Infrared Spectroscopy. Appl. Spectrosc. 2016, 50, 774–780. [Google Scholar] [CrossRef] [Green Version]
- Paroli, R.M.; Lara, J.; Hechler, J.-J.; Cole, K.C.; Butler, I.S. Quantitative Analysis of Monomer Composition in Ethylene-Propylene Block Copolymers by FT-IR Spectroscopy. Appl. Spectrosc. 2016, 41, 319–320. [Google Scholar] [CrossRef]
- Roshan, T.; Rizzardo, E.; Chiefari, J.; Krstina, J.; Moad, G.; Postma, A.; Thang, S.H. Living Polymers by the Use of Trithiocarbonates as Reversible Addition-Fragmentation Chain Transfer (RAFT) Agents: ABA Triblock Copolymers by Radical Polymerization in Two Steps. Macromolecules 2000, 33, 243–245. [Google Scholar]
- Siljanovska Petreska, G.; Auschra, C.; Paulis, M. Confinement driven crystallization of ABA crystalline-soft-crystalline block copolymers synthesized via RAFT mediated miniemulsion polymerization. Polymer 2018, 158, 327–337. [Google Scholar] [CrossRef]
- Yuan, J.J.; Ma, R.; Gao, Q.; Wang, Y.F.; Cheng, S.Y.; Feng, L.X.; Fan, Z.Q.; Jiang, L. Synthesis and characterization of polystyrene/poly(4-vinylpyridine) triblock copolymers by reversible addition-fragmentation chain transfer polymerization and their self-assembled aggregates in water. J. Appl. Polym. Sci. 2003, 89, 1017–1025. [Google Scholar] [CrossRef]
- Aba, W.; Copolymers, H.B. Mechanical and Morphological Properties of Waterborne ABA Hard-Soft-Hard Block Copolymers Synthesized by Means of RAFT Miniemulsion Polymerization. Polymers 2019, 11, 1259. [Google Scholar]
- Quirk, R.P.; Pickel, D.L. Controlled End-Group Functionalization (Including Telechelics). Polym. Sci. A Compr. Ref. 2012, 6, 351–412. [Google Scholar]
- Moad, G.; Rizzardo, E.; Thang, S.H. Living radical polymerization by the RAFT process–a third update. Aust. J. Chem. 2012, 65, 985–1076. [Google Scholar] [CrossRef]
- Moad, G.; Rizzardo, E.; Thang, S.H. Radical addition–fragmentation chemistry in polymer synthesis. Polymer 2008, 29, 1079–1131. [Google Scholar] [CrossRef] [Green Version]
- Semsarilar, M.; Abetz, V. Polymerizations by RAFT: Developments of the Technique and Its Application in the Synthesis of Tailored (Co)polymers. Macromol. Chem. Phys. 2020, 222, 2000311. [Google Scholar] [CrossRef]
- Lavrov, N.A. Characteristics of the Alkaline Hydrolysis of N-Vinyl and Acrylic Polymers. Int. Polym. Sci. Technol. 2018, 29, 38–45. [Google Scholar] [CrossRef] [Green Version]
- Cerrada, M.L.; Sánchez-chaves, M.; Ruiz, C.; Fernández-García, M. Specific lectin interactions and temperature-induced reversible gels in novel water-soluble glycopolymers bearing maltotrionolactone pendant groups. J. Polym. Sci. Part A Polym. Chem. 2010, 48, 719–729. [Google Scholar] [CrossRef]
- Bordegé, V.; Muñoz-Bonilla, A.; León, O.; Sánchez-Chaves, M.; Cuervo-Rodríguez, R.; Fernández-García, M. Glycopolymers with glucosamine pendant groups: Copolymerization, physico-chemical and interaction properties. React. Funct. Polym. 2011, 71, 1–10. [Google Scholar] [CrossRef]
- Cervantes-Uc, J.M.; Cauich-Rodríguez, J.V.; Vázquez-Torres, H.; Licea-Claveríe, A. TGA/FTIR study on thermal degradation of polymethacrylates containing carboxylic groups. Polym. Degrad. Stab. 2006, 91, 3312–3321. [Google Scholar] [CrossRef]
- Rai, V.K.; Mishra, N.; Yadav, K.S.; Yadav, N.P. Nanoemulsion as pharmaceutical carrier for dermal and transdermal drug delivery: Formulation development, stability issues, basic considerations and applications. J. Control. Release 2018, 270, 203–225. [Google Scholar] [CrossRef]
- Wang, Y.; Gao, X.; Kuriyavar, S.; Bourne, D.; Grady, B.; Chen, K.; Dormer, K.; Kopke, R.D. Incorporation, Release, and Effectiveness of Dexamethasone in Poly(Lactic-Co-Glycolic Acid) Nanoparticles for Inner Ear Drug Delivery. J. Nanotechnol. Eng. Med. 2011, 2, 011013. [Google Scholar] [CrossRef]
- Marsden, H.R.; Gabrielli, L.; Kros, A. Rapid preparation of polymersomes by a water addition/solvent evaporation method. Polym. Chem. 2010, 1, 1512. [Google Scholar] [CrossRef]
- Zashikhina, N.; Sharoyko, V.; Antipchik, M.; Tarasenko, I.; Anufrikov, Y.; Lavrentieva, A.; Tennikova, T.; Korzhikova-Vlakh, E. Novel Formulations of C-Peptide with Long-Acting Therapeutic Potential for Treatment of Diabetic Complications. Pharmaceutics 2019, 11, 27. [Google Scholar] [CrossRef] [Green Version]
- Su, F.; Yun, P.; Li, C.; Li, R.; Xi, L.; Wang, Y.; Chen, Y.; Li, S. Novel self-assembled micelles of amphiphilic poly(2-ethyl-2-oxazoline) -poly(L-lactide) diblock copolymers for sustained drug delivery. Colloids Surf. A Physicochem. Eng. Asp. 2019, 566, 120–127. [Google Scholar] [CrossRef]
- Tang, J.; Yao, J.; Shi, J.; Xiao, Q.; Zhou, J.; Chen, F. Synthesis, characterization, drug-loading capacity and safety of novel pH-independent amphiphilic amino acid copolymer micelles. Pharmazie 2012, 67, 756–764. [Google Scholar]
- Kita-Tokarczyk, K.; Grumelard, J.; Haefele, T.; Meier, W. Block copolymer vesicles–Using concepts from polymer chemistry to mimic biomembranes. Polymer 2005, 46, 3540–3563. [Google Scholar] [CrossRef] [Green Version]
- Bhattacharjee, S.; Ershov, D.; Fytianos, K.; van der Gucht, J.; Alink, G.M.; Rietjens, I.M.C.M.; Marcelis, A.T.M.; Zuilhof, H. Cytotoxicity and cellular uptake of tri-block copolymer nanoparticles with different size and surface characteristics. Part. Fibre Toxicol. 2012, 9, 1–19. [Google Scholar] [CrossRef] [Green Version]
- Kong, B.; Seog, J.H.; Graham, L.M.; Lee, S.B. Experimental considerations on the cytotoxicity of nanoparticles. Nanomedicine 2011, 6, 929. [Google Scholar] [CrossRef] [Green Version]
- Binnemars-Postma, K.A.; Ten Hoopen, H.W.; Storm, G.; Prakash, J. Differential uptake of nanoparticles by human M1 and M2 polarized macrophages: Protein corona as a critical determinant. Nanomedicine 2016, 11, 2889–2902. [Google Scholar] [CrossRef] [PubMed]
- Vonarbourg, A.; Passirani, C.; Saulnier, P.; Benoit, J.P. Parameters influencing the stealthiness of colloidal drug delivery systems. Biomaterials 2006, 27, 4356–4373. [Google Scholar] [CrossRef]
- Amoozgar, Z.; Yeo, Y. Recent advances in stealth coating of nanoparticle drug delivery systems. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 2012, 4, 219–233. [Google Scholar] [CrossRef] [Green Version]
- Jauhari, S.; Singh, S.; Dash, A.K. Paclitaxel. Profiles Drug Subst. Excip. Relat. Methodol. 2009, 34, 299–344. [Google Scholar]
- Jiang, M.; Han, X.; Guo, W.; Li, W.; Chen, J.; Ren, G.; Sun, B.; Wang, Y.; He, Z. Star-shape paclitaxel prodrug self-assembled nanomedicine: Combining high drug loading and enhanced cytotoxicity. RSC Adv. 2016, 6, 109076–109082. [Google Scholar] [CrossRef]
- Alani, A.W.G.; Bae, Y.; Rao, D.A.; Kwon, G.S. Polymeric micelles for the pH-dependent controlled, continuous low dose release of paclitaxel. Biomaterials 2010, 31, 1765–1772. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Korzhikov, V.A.; Diederichs, S.; Nazarova, O.V.; Vlakh, E.G.; Kasper, C.; Panarin, E.F.; Tennikova, T.B. Water-soluble aldehyde-bearing polymers of 2-deoxy-2-methacrylamido-D- glucose for bone tissue engineering. J. Appl. Polym. Sci. 2008, 108. [Google Scholar] [CrossRef]
- Sivakumar, P.A.; Panduranga Rao, K. Stable Polymerized Cholesteryl Methacrylate Liposomes for Vincristine Delivery. Biomed. Microdevices 2001, 3, 143–148. [Google Scholar] [CrossRef]
- Sivtsov, E.V.; Gostev, A.I.; Lavrov, N.A. Copolymerization of N-vinylsuccinimide with butyl acrylate in an electron-donor medium of tertiary aminese. Russ. J. Appl. Chem. 2009, 82, 1281–1287. [Google Scholar] [CrossRef]
- Sivtsov, E.; Chernikova, E.; Gostev, A.; Garina, E. Controlled free-radical copolymerization of n-vinyl succinimide and n-butyl acrylate via a reversible addition-fragmentation chain transfer (RAFT) technique. Macromol. Symp. 2010, 296, 112–120. [Google Scholar] [CrossRef]
Sample | Hydrophilic Block a | Hydrophobic Block | ||||
---|---|---|---|---|---|---|
Mn | Mw | Đ | DP | DP | Mn | |
PMAG | PChMA b | |||||
#1 | 4600 | 4800 | 1.05 | 18 | 18 | 8100 |
PVSI | PChMA c | |||||
#2 | 14,300 | 19,600 | 1.37 | 114 | 27 | 12,150 |
#3 | 2800 | 3000 | 1.10 | 22 | 43 | 19,350 |
Block-Copolymer | DH (nm) | PDI | ζ-Potential (mV) | |
---|---|---|---|---|
DLS | NTA | |||
PMAG-b-PChMA (#1) | 203 ± 65 | 191 ± 75 | 0.16 | −14.5 ± 1.7 |
PVSAA-b-PChMA-b-PVSAA (#h2) | 230 ± 90 | 219 ± 79 | 0.20 | −66.2 ± 2.1 |
PVSAA-b-PChMA-b-PVSAA (#h3) | 220 ± 85 | – | 0.20 | −19.0 ± 0.1 |
Formulation | Loading (µg/mg of NPs) | IC50 (ng/mL) |
---|---|---|
Free PTX | − | 4.4 ± 0.4 |
PTX LANS | − | 4.9 ± 0.3 |
PTX loaded in PMAG-b-PChMA NPs | 50 | 16.6 ± 1.0 |
PTX loaded in PMAG-b-PChMA NPs | 100 | 25.1 ± 0.9 |
PTX loaded in PVSAA-b-PChMA-b-PVSAA NPs | 50 | 10.6 ± 0.5 |
PTX loaded in PVSAA-b-PChMA-b-PVSAA NPs | 100 | 11.3 ± 1.0 |
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Levit, M.; Vdovchenko, A.; Dzhuzha, A.; Zashikhina, N.; Katernyuk, E.; Gostev, A.; Sivtsov, E.; Lavrentieva, A.; Tennikova, T.; Korzhikova-Vlakh, E. Self-Assembled Nanoparticles Based on Block-Copolymers of Poly(2-Deoxy-2-methacrylamido-d-glucose)/Poly(N-Vinyl Succinamic Acid) with Poly(O-Cholesteryl Methacrylate) for Delivery of Hydrophobic Drugs. Int. J. Mol. Sci. 2021, 22, 11457. https://doi.org/10.3390/ijms222111457
Levit M, Vdovchenko A, Dzhuzha A, Zashikhina N, Katernyuk E, Gostev A, Sivtsov E, Lavrentieva A, Tennikova T, Korzhikova-Vlakh E. Self-Assembled Nanoparticles Based on Block-Copolymers of Poly(2-Deoxy-2-methacrylamido-d-glucose)/Poly(N-Vinyl Succinamic Acid) with Poly(O-Cholesteryl Methacrylate) for Delivery of Hydrophobic Drugs. International Journal of Molecular Sciences. 2021; 22(21):11457. https://doi.org/10.3390/ijms222111457
Chicago/Turabian StyleLevit, Mariia, Alena Vdovchenko, Apollinariia Dzhuzha, Natalia Zashikhina, Elena Katernyuk, Alexey Gostev, Eugene Sivtsov, Antonina Lavrentieva, Tatiana Tennikova, and Evgenia Korzhikova-Vlakh. 2021. "Self-Assembled Nanoparticles Based on Block-Copolymers of Poly(2-Deoxy-2-methacrylamido-d-glucose)/Poly(N-Vinyl Succinamic Acid) with Poly(O-Cholesteryl Methacrylate) for Delivery of Hydrophobic Drugs" International Journal of Molecular Sciences 22, no. 21: 11457. https://doi.org/10.3390/ijms222111457