Ayça Bal ÖZTÜRK, Nesrin OĞUZ, Hande Tekarslan ŞAHİN, Serkan EMİK, Emine ALARÇİN

Design of an amphiphilic hyperbranched core/shell-type polymeric nanocarrier platform for drug delivery

An amphiphilic core/shell-type polymer-based drug carrier system HPAE- PCL- b -MPEG , composed of hyperbranched poly aminoester -based polymer HPAE as the core building block and poly ethylene glycol - b - poly ε-caprolactone diblock polymers MPEG- b -PCL as the shell building block, was designed. The synthesized polymers were characterized with FTIR, 1 H NMR, 13 C NMR, and GPC analysis. Monodisperse HPAE-PCL- b - MPEG nanoparticles with dimensions of

Keywords:

Hyperbranched polymer, poly aminoester, nanoparticle, drug delivery, 5-fluorouracil,

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1. Lukowiak MC, Thota BN, Haag B. Dendritic core–shell systems as soft drug delivery nanocarriers. Biotecnology Advances 2015; 33 (6): 1327-1341. doi: 10.1016/j.biotechadv.2015.03.014
2. Yiyun C, Tongwen X. Dendrimers as potential drug carriers. Part I. Solubilization of non-steroidal anti-inflammatory drugs in the presence of polyamidoamine dendrimers. European Journal of Medicinal Chemistry 2005; 40 (11): 1188-1192. doi: 10.1016/j.ejmech.2005.06.010
3. Lukyanov AN, Torchilin VP. Micelles from lipid derivatives of water-soluble polymers as delivery systems for poorly soluble drugs. Advanced Drug Delivery Reviews 2004; 56 (9): 1273-1289. doi: 10.1016/j.addr.2003.12.004
4. Müller RH, Jacobs C, Kayser O. Nanosuspensions as particulate drug formulations in therapy: rationale for development and what we can expect for the future. Advanced Drug Delivery Reviews 2001; 47 (eq1): 3-19. doi: 10.1016/S0169-409X(00)00118-6
5. Hassan S, Prakash G, Ozturk AB, Saghazadeh S, Sohail MF et al. Evolution and clinical translation of drug delivery nanomaterials. Nano Today 2017; 15: 91-106. doi: 10.1016/j.nantod.2017.06.008
6. Caminade AM, Yan D, Smith DK. Dendrimers and hyperbranched polymers. Chemical Society Reviews 2015; 44 (12): 3870-3873. doi: 10.1039/C5CS90049B
7. Zhang L, Zhou Y, Shi G, Sang X, Ni C. Preparations of hyperbranched polymer nano micelles and the pH/redox controlled drug release behaviors. Materials Science and Engineering C 2017; 79: 116-122. doi: 10.1016/j.msec.2017.05.027
8. Kurniasih IN, Keilitz J, Haag R. Dendritic nanocarriers based on hyperbranched polymers. Chemical Society Reviews 2015; 44 (12): 4145-4164. doi: 10.1039/c4cs00333k
9. Bal-Öztürk A, Cevher E, Pabuccuoğlu S, Özgümüş S. pH sensitive functionalized hyperbranched polyester based nanoparticulate system for the receptor-mediated targeted cancer therapy. International Journal of Polymeric Materials and Polymeric Biomaterials 2018; 68 (8): 1-16. doi: 10.1080/00914037.2018.1452226
10. Zhang L, Hu CH, Cheng SX, Zhuo RX. Hyperbranched amphiphilic polymer with folate mediated targeting property. Colloids and Surfaces B Biointerfaces 2010; 79 (eq2): 427-433. doi: 10.1016/j.colsurfb.2010.05.014
11. Bal A, Cevher E, Pabuccuoğlu SK. Hydroxyl-functionalized hyperbranched aliphatic polyesters based On 1, 1, 1-Tris (hydroxymethyl) propane (Tmp) as a core molecule: synthesis and characterization. Sigma Journal of Engineering and Natural Sciences - Sigma Mühendislik ve Fen Bilimleri Dergisi 2017; 35 (eq2): 239-251.
12. Grossen P, Witzigmann D, Sieber S, Huwyler J. PEG-PCL-based nanomedicines: a biodegradable drug delivery system and its application. Journal of Controlled Release 2017; 260: 46-60. doi: 10.1016/j.jconrel.2017.05.028
13. Kim HJ, Kwon MS, Choi JS, Kim BH, Yoon JK et al. Synthesis and characterization of poly (amino ester) for slow biodegradable gene delivery vector. Bioorganic & Medicinal Chemistry 2007; 15 (4): 1708-1715. doi: 10.1016/j.bmc.2006.12.004
14. Shuai X, Merdan T, Unger F, Wittmar M, Kissel T. Novel biodegradable ternary copolymers hy-PEI-g-PCL-bPEG: synthesis, characterization, and potential as efficient nonviral gene delivery vectors. Macromolecules 2003; 36 (15): 5751-5759. doi: 10.1021/ma034430w
15. Hatton FL, Chambon P, Savage AC, Rannard SP. Role of highly branched, high molecular weight polymer structures in directing uniform polymer particle formation during nanoprecipitation. Chemical Communications 2016; 52 (20): 3915-3918. doi: 10.1039/C6CC00611F
16. Huang H, Shi H, Liu J, Min Y, Wang Y et al. Co-delivery of all-trans-retinoic acid enhances the anti-metastasis effect of albumin-bound paclitaxel nanoparticles. Chemical Communications 2017; 53 (eq1): 212-215. doi: 10.1039/C6CC08146K
17. Chen R, Wang L. Synthesis of an amphiphilic hyperbranched polymer as a novel pH-sensitive drug carrier. Royal Society of Chemistry Advances 2015; 5 (26): 20155-20159. doi: 10.1039/C4RA16935B
18. Chen H, Kong J. Hyperbranched polymers from A2 + B3 strategy: recent advances in description and control of fine topology. Polymer Chemistry 2016; 7 (22): 3643-3663. doi: 10.1039/C6PY00409A
19. Hawker CJ, Lee R, Fréchet JM. One-step synthesis of hyperbranched dendritic polyesters. Journal of American Chemical Society 1991; 113 (12): 4583-4588. doi: 10.1021/ja00012a030
20. Zhang J, Zheng Y, Yu P, Mo S, Wang R. The synthesis of functionalized carbon nanotubes by hyperbranched poly (amine-ester) with liquid-like behavior at room temperature. Polymer 2009; 50 (13): 2953-2957. doi: 10.1016/j.polymer.2009.04.042
21. Pang Y, Liu J, Su Y, Wu J, Zhu L et al. Design and synthesis of thermo-responsive hyperbranched poly (amineester)s as acid-sensitive drug carriers. Polymer Chemistry 2011; 2 (8): 1661-1670. doi: 10.1039/C1PY00053E
22. Jiang M, Wu Y, He Y, Nie J. Micelles formed by self-assembly of hyperbranched poly [(amine-ester)-co-(D, Llactide)](HPAE-co-PLA) copolymers for protein drug delivery. Polymer International 2009; 58 (eq1): 31-39. doi: 10.1002/pi.2489
23. Feng R, Song Z, Zhai G. Preparation and in vivo pharmacokinetics of curcumin-loaded PCL-PEG-PCL triblock copolymeric nanoparticles. International Journal of Nanomedicine 2012; 7: 4089. doi: 10.2147/IJN.S33607
24. Cuong NV, Hsieh MF, Chen YT, Liau I. Synthesis and characterization of PEG–PCL–PEG triblock copolymers as carriers of doxorubicin for the treatment of breast cancer. Journal of Applied Polymer Science 2010; 117 (6): 3694-3703. doi: 10.1002/app.32266
25. Gou M, Zheng X, Men K, Zhang J, Wang B et al. Self-assembled hydrophobic honokiol loaded MPEG-PCL diblock copolymer micelles. Pharmaceutical Research 2009; 26 (9): 2164-2173. doi: 10.1007/s11095-009-9929-8
26. Azouz LH, Dahmoune F, Rezgui F, G’Sell C. Full factorial design optimization of anti-inflammatory drug release by PCL–PEG–PCL microspheres. Materials Science and Engineering C 2016; 58: 412-419. doi: 10.1016/j.msec.2015.08.058
27. Liu CB, Gong CY, Huang MJ, Wang JW, Pan YF et al. Thermoreversible gel-sol behavior of biodegradable PCL-PEG-PCL triblock copolymer in aqueous solutions. Journal of Biomedical Materials Research B Applied Biomaterials 2008; 84 (eq1): 165-175. doi: 10.1002/jbm.b.30858
28. Malkani A, Date AA, Hegde D. Celecoxib nanosuspension: Single-step fabrication using a modified nanoprecipitation method and in vivo evaluation. Drug Delivery and Translational Research 2014; 4 (4): 365-376. doi: 10.1007/s13346-014-0201-3
29. Hussain Z, Sahudin S. Preparation, characterisation and colloidal stability of chitosan-tripolyphosphate nanoparticles: Optimisation of formulation and process parameters. International Journal of Pharmacy and Pharmaceutical Sciences 2016; 8 (eq3): 297-308.
30. Priyanka K, Sahu PL, Singh S. Optimization of processing parameters for the development of Ficus religiosa L. extract loaded solid lipid nanoparticles using central composite design and evaluation of antidiabetic efficacy. Journal of Drug Delivery Science and Technology 2018; 43: 94-102. doi: 10.1016/j.jddst.2017.08.006
31. El-Naggar ME, El-Rafie MH, El-Sheikh MA, El-Feky GS, Hebeish A. Synthesis, characterization, release kinetics and toxicity profile of drug-loaded starch nanoparticles. International Journal of Biological Macromolecules 2015; 81: 718-729. doi: 10.1016/j.ijbiomac.2015.09.005
32. Farhadian A, Dounighi NM, Avadi M. Enteric trimethyl chitosan nanoparticles containing hepatitis B surface antigen for oral delivery. Human Vaccines & Immunotherapeutics 2015; 11 (12): 2811-2818. doi: 10.1080/21645515.2015.1053663
33. Torchilin VP. Targeted pharmaceutical nanocarriers for cancer therapy and imaging. Journal of the American Association of Pharmaceutical Scientists 2007; 9 (eq2): E128-E147. doi: 10.1208/aapsj0902015
34. Quignard S, Masse S, Coradin T. Silica-based nanoparticles for intracellular drug delivery. In: Prokop A (editor). Intracellular Delivery. Dordrecht, the Netherlands: Springer, 2011, pp. 333-361.
35. Cevher E, Salomon SK, Makrakis A, Li XW, Brocchini S et al. Development of chitosan–pullulan composite nanoparticles for nasal delivery of vaccines: optimisation and cellular studies. Journal of Microencapsulation 2015
32 (8): 755-768. doi: 10.3109/02652048.2015.1073392
36. Lee MK, Lim SJ, Kim CK. Preparation, characterization and in vitro cytotoxicity of paclitaxel-loaded sterically stabilized solid lipid nanoparticles. Biomaterials 2007; 28 (12): 2137-2146. doi: 10.1016/j.biomaterials.2007.01.014
37. Popat A, Liu J, Lu GQ, Qiau SZ. A pH-responsive drug delivery system based on chitosan coated mesoporous silica nanoparticles. Journal of Materials Chemistry 2012; 22 (22): 11173-11178. doi: 10.1039/C2JM30501A
38. Bhat SK, Keshavayya J, Kulkarni VH, Reddy VK, Kulkarni PV et al. Preparation and characterization of crosslinked chitosan microspheres for the colonic delivery of 5-fluorouracil. Journal of Applied Polymer Science 2012; 125 (eq3): 1736-1744. doi: 10.1002/app.35654
39. Das S, Ng WK, Tan RB. Are nanostructured lipid carriers (NLCs) better than solid lipid nanoparticles (SLNs): development, characterizations and comparative evaluations of clotrimazole-loaded SLNs and NLCs? European Journal of Pharmaceutical Sciences 2012; 47 (eq1): 139-151. doi: 10.1016/j.ejps.2012.05.010
40. Yoo JW, Chambers E, Mitragotri S. Factors that control the circulation time of nanoparticles in blood: challenges, solutions and future prospects. Current Pharmaceutical Design 2010; 16 (21): 2298-2307. doi: 10.2174/138161210791920496
41. Kumar G, Shafiq N, Malhotra S. Drug-loaded PLGA nanoparticles for oral administration: fundamental issues and challenges ahead. Critical Reviews in Therapeutic Drug Carrier Systems 2012; 29 (eq2): 149-182. doi: 10.1615/CritRevTherDrugCarrierSyst.v29.i2.20
42. Mansouri S, Cuie Y, Winnik F, Shi Q, Lavigne P et al. Characterization of folate-chitosan-DNA nanoparticles for gene therapy. Biomaterials 2006; 27 (9): 2060-2065. doi: 10.1016/j.biomaterials.2005.09.020
43. He Y, Park K. Effects of the microparticle shape on cellular uptake. Molecular Pharmaceutics 2016; 13 (7): 2164- 2171. doi: 10.1021/acs.molpharmaceut.5b00992
44. Chouhan R, Bajpai AK. An in vitro release study of 5-fluoro-uracil (5-FU) from swellable poly-(2-hydroxyethyl methacrylate) (PHEMA) nanoparticles. Journal of Materials Science: Materials in Medicine 2009; 20 (5): 1103- 1114. doi: 10.1007/s10856-008-3677-x
45. Sun ZJ, Chen C, Sun MZ, Ai CH, Lu XL et al. The application of poly (glycerol–sebacate) as biodegradable drug carrier. Biomaterials 2009; 30 (28): 5209-5214. doi: 10.1016/j.biomaterials.2009.06.007
46. Bhat SK, Keshavayya J, Kulkarni VH, Reddy VK, Kulkarni PV et al. Preparation and characterization of crosslinked chitosan microspheres for the colonic delivery of 5-fluorouracil. Journal of Applied Polymer Science 2012; 125 (eq3): 1736-1744. doi: 10.1002/app.35654
47. Yassin AEB, Anwer MK, Mowafy HA, El-Bagory IM, Bayomi MA et al. Optimization of 5-flurouracil solid-lipid nanoparticles: a preliminary study to treat colon cancer. International Journal of Medical Sciences 2010; 7 (6): 398. doi: 10.7150/ijms.7.398
48. Hu YX, Chang J, Guo Y, Yuan XB, Kang CS et al. Preparation and evaluation of 5-FU/PLGA/gene nanoparticles. Key Engineering Materials 2005; 288-289: 147-150. doi: 10.4028/www.scientific.net/KEM.288-289.147
49. Khang G, Kim SW, Cho JC, Rhee JM, Yoon SC et al. Preparation and characterization of poly (3-hydroxybutyrateco-3-hydroxyvalerate) microspheres for the sustained release of 5-fluorouracil. Bio-medical Materials and Engineering 2001; 11 (eq2): 89-103.
50. Fan YL, Fan BY, Li Q, Di HX, Meng XY et al. Preparation of 5-fluorouracil-loaded nanoparticles and study of interaction with gastric cancer cells. Asian Pacific Journal of Cancer Prevention 2013; 15: 7611-7615. doi: 10.7314/APJCP.2014.15.18.7611
51. Aryal S, Prabaharan M, Pilla S, Gong S. Biodegradable and biocompatible multi-arm star amphiphilic block copolymer as a carrier for hydrophobic drug delivery. International Journal of Biological Macromolecules 2009; 44 (4): 346-352. doi: 10.1016/j.ijbiomac.2009.01.007
52. Zhang Y, Li J, Lang M, Tang X, Li L et al. Folate-functionalized nanoparticles for controlled 5-fluorouracil delivery. Journal of colloid and interface science 2011; 354 (eq1): 202-209. doi: 10.1016/j.jcis.2010.10.054
53. Niwa T, Takeuchi H, Hino T, Kunou N, Kawash Y. Preparations of biodegradable nanospheres of water-soluble and insoluble drugs with D, L-lactide/glycolide copolymer by a novel spontaneous emulsification solvent diffusion method, and the drug release behavior. Journal of Controlled Release 1993; 25 (1-2): 89-98. doi: 10.1016/0168- 3659(93)90097-O
54. Akbuga J, Bergişadi N. 5-Fluorouracil-loaded chitosan microspheres: preparation and release characteristics. Journal of Microencapsulation 1996; 13 (eq2): 161-168. doi: 10.3109/02652049609052904
55. McCarron PA, Woolfson AD, Keating SM. Sustained release of 5-fluorouracil from polymeric nanoparticles. Journal of Pharmacy and Pharmacology 2000; 52 (12): 1451-1459. doi: 10.1211/0022357001777658
56. Maghsoudi A, Shojaosadati SA, Farahani EV. 5-Fluorouracil-loaded BSA nanoparticles: formulation optimization and in vitro release study. Journal of the American Association of Pharmaceutical Scientists 2008; 9 (4): 1092-1096. doi: 10.1208/s12249-008-9146-5
57. Wang Y, Li P, Chen L, Gao W, Zeng F et al. Targeted delivery of 5-fluorouracil to HT-29 cells using high efficient folic acid-conjugated nanoparticles. Drug Delivery 2015; 22 (eq2): 191-198. doi: 10.3109/10717544.2013.875603
58. Rastegar A, Nazari S, Allahabadi A, Falanji F, Akbari-Dourbash FA et al. Antibacterial activity of amino- and amido- terminated poly (amidoamine)-G6 dendrimer on isolated bacteria from clinical specimens and standard strains. Medical Journal of the Islamic Republic of Iran 2017; 31: 64. doi: 10.14196/mjiri.31.64
59. Rashid HA. Preparation and characterization of PLGA loaded nanoparticles obtained from D. melanoxylon Roxb. leaves for their antiproliferative and antidiabetic activity. International Journal of Green Pharmacy 2017; 11 (03): 1154. doi: 10.22377/ijgp.v11i03.1154
60. Joseph MM, Aravind SR, Varghese S, Mini S, Sreelekha TT. PST-Gold nanoparticle as an effective anticancer agent with immunomodulatory properties. Colloids and Surfaces B Biointerfaces 2013; 104: 32-39. doi: 10.1016/j.colsurfb.2012.11.046