UPSI Digital Repository (UDRep)
|
UPSI Digital Repository (UDRep)
|
|
|
| ||||||||||||||||||||
| Abstract : Universiti Pendidikan Sultan Idris |
| Novel Pentaerythritol (PTL)- and dipentaerythritol (DPTL)-cored dendrimer-like star polymers with AB2 miktoarms [A =poly(L-Lactide); poly(ethylene glycol)-folate] (1g and 2g) were synthesized and characterized by proton magnetic resonance spectroscopy, fourier transform infrared, gel permeation chromatography and differential scanning calorimetric techniques. Anticancer drug doxorubicin was encapsulated into the star polymer nanoparticles using nanoprecipitation technique. The doxorubicin-loaded nanoparticles of the star polymer with PTL core (1g-NPs-DOX) and DPTL core (2g-NPs-DOX) were spherical and had average diameters of 185.88 ± 27.53 nm and 203.66 ± 20.69 nm, and zeta potential of −19.54 ± 0.57 mV and − 14.77 ± 1.16 mV, respectively. 2g-NPs-DOX had higher doxorubicin loading and encapsulation efficiency (14.59% ± 0.001; 87.54% ± 0.003) than those of 1g-NPs-DOX (12.88% ± 0.006; 77.29% ± 0.039). In vitro release studies showed that an initial burst release of doxorubicin was followed by a sustained release over 7 days, which were significantly higher at pH 5.3 than at pH 7.4. Both drug-free nanoparticles 1g-NPs and 2g-NPs exhibited low cytotoxic effect against MCF-7 and MCF-10a with over 80% cell viability at maximum concentration (100 μM) after 72 h of incubation. Due to sustained release, the IC50 values (72 h) of 1g-NPs-DOX and 2g-NPs-DOX against MCF-7 cells were 22.5 μM and 19.5 μM respectively, as compared to 41.0 μM and 32.0 μM against MCF-10a cells, which suggested that 1g-NPs-DOX and 2g-NPs-DOX are more effective in inhibiting the breast cancer cell viability. Hence, the dendrimer-like star polymers, 1g and 2g, showed good potential as nanocarriers for preferential delivery of doxorubicin to the breast cancer cells |
| References |
1. Xiao RZ, Zeng ZW, Zhou G.L, Wang JJ, Li FZ, Wang AM (2010) Recent advances in PEG-PLA block copolymer nanoparticles. Int J Nanomedicine 5:1057–1065 2. Gaucher G, Dufresne MH, Sant VP, Kang N, Maysinger D, Leroux JC (2005) Block copolymer micelles: preparation, characterization and application in drug delivery. J Control Release 109:169–188 3. Dong Y, Feng SS (2007) In vitro and in vivo evaluation of methoxy polyethylene glycol-polylactide (MPEG-PLA) nanoparticles for small-molecule drug chemotherapy. Biomaterials 28:4154–4160 4. Huang YY, Chung TW, Tzeng TW (1997) Drug release from PLA/ PEG microparticulates. Int J Pharm 156:9–15 5. Sheth M, Kumar RA, Davé V, Gross RA, McCarthy SP (1997) Biodegradable polymer blends of poly(lactic acid) and poly(ethylene glycol). J Appl Polym Sci 66:1495–1505 6. Hami Z, Amini M, Ghazi-Khansari M, Rezayat SM, Gilani K (2014) Synthesis and in vitro evaluation of a pH-sensitive PLAPEG-folate based polymeric micelle for controlled delivery of docetaxel. Colloids Surf B Biointerfaces 116:309–317 7. Beletsi A, Leontiadis L, Klepetsanis P, Ithakissios DS, Avgoustakis K (1999) Effect of preparative variables on the properties of poly(dl-lactide-co-glycolide)-methoxypoly(ethyleneglycol) copolymers related to their application in controlled drug delivery. Int J Pharm 182:187–197 8. Morlock M, Kissel T, Li YX, Koll H, Winter G (1998) Erythropoietin loaded microspheres prepared from biodegradable LPLG-PEO-LPLG triblock copolymers: protein stabilization and in-vitro release properties. J Control Release 56:105–115 9. Kissel T, Li Y, Unger F (2002) ABA-triblock copolymers from biodegradable polyester A-blocks and hydrophilic poly(ethylene oxide) B-blocks as a candidate for in situ forming hydrogel delivery systems for proteins. Adv Drug Del Rev 54:99–134 10. Hu X, Xu J, Zhong G, Luo X, Li Z (2011) Shear induced crystallization of poly(L-lactide) and poly(ethylene glycol) (PLLA-PEGPLLA) copolymers with different block length. J Pol Res 18:675–680 11. Baimark T, Pasee S, Rungseesantivanon W, Prakymoramas N (2019) Flexible and high heat-resistant stereocomplex PLLAPEG-PLLA/PDLA blends prepared by melt process: effect of chain extension. J Pol Res 26:218 12. Jeong B, Bae YH, Lee DS, Kim SW (1997) Biodegradable block copolymers as injectable drug-delivery systems. Nature 388:860–862 13. Jeong B, Bae YH, Kim SW (2000) Drug release from biodegradable injectable thermosensitive hydrogel of PEG-PLGA-PEG triblock copolymers. J Control Release 63:155–163 14. Huh KM, Bae YH (1999) Synthesis and characterization of poly(- ethylene glycol)/poly(l-lactic acid) alternating multiblock copolymers. Polymer 40:6147–6155 15. Bae YH, Huh KM, Kim Y, Park KH (2000) Biodegradable amphiphilic multiblock copolymers and their implications for biomedical applications. J Control Release 64:3–13 16. Hrkach JS, Peracchia MT, Domb A, Lotan N, Robert L (1997) Nanotechnology for biomaterials engineering: structural characterization of amphiphilic polymeric nanoparticles by 1 H NMR spectroscopy. Biomaterials 18:27–30 17. Breitenbach A, Li YX, Kissel T (2000) Branched biodegradable polyesters for parenteral drug delivery systems. J Control Release 64:167–178 18. Chong YK, Zainol I, Ng CH, Ooi IH (2019) Miktoarm star polymers nanocarrier: synthesis, characterisation, and in-vitro drug release study. J Pol Res 26:79 19. Hadjichristidis N, Iatrou H, Pitsikalis M, Driva P, Sakellariou G, Chatzichristidi M (2012) Polymers with star-related structures: synthesis, properties, and applications. Polymer science: a comprehensive reference. Elsevier, Amsterdam, pp 29–111 20. Hu F, Neoh KG, Kang ET (2009) Synthesis of folic acid functionalized PLLA-b-PPEGMA nanoparticles for Cancer cell targeting. Macromol Rapid Commun 30:609–614 21. Fernandez M, Javaid F, Chudasama V (2018) Advances in targeting the folate receptor in the treatment/imaging of cancers. Chem Sci 9:790–810 22. Kim H, Jo A, Baek S, Lim D, Park SY, Cho SK, Chung JW, Yoon J (2017) Synergistically enhanced selective intracellular uptake of anticancer drug carrier comprising folic acid-conjugated hydrogels containing magnetite nanoparticles. Sci Rep 7:41090 23. Kadota J, Pavlovic D, Desvergne JP, Bibal B, Peruch F, Deffieux A (2010) Ring-opening polymerization of L-Lactide catalyzed by an Organocatalytic system combining acidic and basic sites. Macromolecules 43:8874–8879 24. Li D, Ding JX, Tang ZH, Sun H, Zhuang XL, Xu JZ, Chen XS (2012) In vitro evaluation of anticancer nanomedicines based on doxorubicin and amphiphilic Y-shaped copolymers. Int J Nanomedicine 7:2687–2697 25. Ayen WY, Garkhal K, Kumar N (2011) Doxorubicin-loaded (PEG)3-PLA Nanopolymersomes: effect of solvents and process parameters on formulation development and In Vitro study. Mol Pharm 8:466–478 26. Trollsås M, Atthoff B, Claesson H, Hedrick JL (2004) Dendritic homopolymers and block copolymers: tuning the morphology and properties. J Polym Sci, Part A: Polym Chem 42:1174–1188 27. Wang L, Cai C, Dong CM (2008) Synthesis, characterization and nanoparticle formation of star-shaped poly(L-lactide) with six arms. Chi J Polym Sci 26:161–169 28. Joung YK, Lee JS, Park KD, Lee S (2008) 6-arm PLLA-PEG block copolymers for micelle formation and controlled drug release. Macromol Res 16:66–69 29. Kim SH, Han YK, Ahn KD, Kim YH, Chang T (1993) Preparation of star-shaped PLA with pentaerytritol and tin occtuate. Macromol Chem Phys 194:3229–3236 30. Pasut G, Scaramuzza S, Schiavon O, Mendichi R, Veronese FM (2005) PEG-epirubicin conjugates with high drug loading. J Bioact Compat Polym 20:213–230 31. Sammet B (2009) 4-Nitrophenyl Chloroformate: a versatile coupling reagent. SYNLETT 18:3050–3051 32. Kadajji VG, Betageri GV (2011) Water soluble polymers for pharmaceutical applications. Polymers 3:1972–2009 33. Valeur E, Bradley M (2009) Amide bond formation: beyond the myth of coupling reagents. Chem Soc Rev 38:606–631 34. Jalabert M, Fraschini C, Prud’homme RE (2007) Synthesis and characterization of poly(L-lactide)s and poly(D-lactide)s of controlled molecular weight. J Polym Sci: Part A: Polym Chem 45: 1944–1955 35. Zhang X, Li Y, Chen X, Wang X, Xu X, Liang Q, Hu J, Jing X (2005) Synthesis and characterization of the paclitaxel/MPEG-PLA block copolymer conjugate. Biomaterials 26:2121–2128 36. Dinc CO, Kibarer G, Guner A (2010) Solubility profiles of poly(- ethylene glycol)/solvent systems. II comparison of thermodynamic parameters from viscosity measurements. J Appl Polym Sci 117:1100–1119 37. Izunobi JU, Higginbotham CL (2011) Polymer molecular weight analysis by 1 H NMR spectroscopy. J Chem Edu 88:1098–1104 38. Govender T, Stolnik S, Garnett MC, Illum L, Davis SS (1999) PLGA nanoparticles prepared by nanoprecipitation: drug loading and release studies of a water soluble drug. J Control Release 57: 171–185 39. Ruan G, Feng SS (2003) Preparation and characterization of poly(lactic acid)–poly(ethylene glycol)–poly(lactic acid) (PLA– PEG–PLA) microspheres for controlled release of paclitaxel. Biomaterials 24:5037–5044 40. Zhao H, Yung LY (2008) Selectivity of folate conjugated polymer micelles against different tumor cells. Int J Pharma 349:256–268 41. Dong Y, Feng SS (2004) Methoxy poly(ethylene glycol)- poly(lactide) (MPEG-PLA) nanoparticles for controlled delivery of anticancer drugs. Biomaterials 25:2843–2849 42. Venkatraman SS, Jie P, Min F, Freddy BY, Gan LH (2005) Micelle-like nanoparticles of PLA-PEG-PLA triblock copolymers as chemotherapeutic carrier. Int J Pharm 298:219–232 43. Jie P, Venkatraman SS, Min F, Freddy BY, Huat GL (2005) Micelle-like nanoparticles of star-branched PEO-PLA copolymers as chemotherapeutic carrier. J Control Release 110:20–33 44. Hira SK, Mishra AK, Ray B, Manna PP (2014) Targeted delivery of doxorubicin-loaded poly (ε-caprolactone)-b-poly (Nvinylpyrrolidone) micelles enhances antitumor effect in lymphoma.PLoS One 9:e94309 45. Manocha B, Margaritis A (2010) Controlled release of doxorubicin from doxorubicin/γ-Polyglutamic acid ionic complex. J Nanomaterials 1-9 46. Brigger I, Dubernet C, Couvreur P (2002) Nanoparticles in cancer therapy and diagnosis. Adv Drug Deliv Rev 54:631–651 47. Matsumoto J, Nakada Y, Sakurai K, Nakamura T, Takahashi Y (1991) Preparation of nanoparticles consisted of poly(L-lactide)- poly(ethylene glycol)-poly(L-lactide) and their evaluation in vitro. Int J Pharm 185:93–101 48. Safra T (2003) Cardiac safety of liposomal anthracyclines. Oncologist 8(Suppl 2):17–24
|
| This material may be protected under Copyright Act which governs the making of photocopies or reproductions of copyrighted materials. You may use the digitized material for private study, scholarship, or research. |