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Abstract

A facile method for synthesis of poly ethylene glycol (PEG)-armed hyperbranched polyoxetanes is presented along with characterization and use in drug delivery. A series of hyperbranched polyoxetanes with multiple PEG arms were synthesized via a one-pot cationic ring-opening polymerization of 3-ethyl-3-hydroxymethyl oxetane (EHMO) and its PEGylated derivative (EPMO), in which the feed mass ratio of EHMO to EPMO was 98:2, 96:4, 74:26, or 17:83. Characterization methods included nuclear magnetic resonance, dynamic light scattering, Fourier transform infrared, differential scanning calorimetry, and scanning electron microscopy. Toxicity of the synthesized polymers to human dermal fibroblasts was evaluated using the MTT assay. Formulation into particles was carried out to encapsulate the anticancer drug camptothecin using the single oil-in-water solvent evaporation method. The resulting drug encapsulated particles were evaluated for antitumor activity using HN12 cells.

Keywords

Anticancer drug delivery hyperbranched polymer PEGylation polyether polyol

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References

Kim

Webster

. Water soluble hyperbranched polyphenylene: “a unimolecular micelle?” J Am Chem Soc 1990; 112(11): 4592–4593.

Hawker

Lee

Frechet

JMJ

. One-step synthesis of hyperbranched dendritic polyesters. J Am Chem Soc 1991; 113(12): 4583–4588.

Wooley

Hawker

Frechet

JMJ

. Hyperbranched macromolecules via a novel double-stage convergent growth approach. J Am Chem Soc 1991; 113(11): 4252–4261.

Hobson

Feast

. Poly(amidoamine) hyperbranched systems: synthesis, structure and characterization. Polymer 1998; 40(5): 1279–1297.

Vogtle

Gestermann

Hesse

. Funct- ional dendrimers. Prog Polym Sci 2000; 25(7): 987–1041.

Tziveleka

Kontoyianni

Sideratou

. Novel functional hyperbranched polyether polyols as prospective drug delivery systems. Macromol Biosci 2006; 6(2): 161–169.

Kawaguchi

Walker

Wilkins

. Double exponential dendrimer growth. J Am Chem Soc 1995; 117(8): 2159–2165.

Gnanou

Lutz

Rempp

. Synthesis of star-shaped poly(ethylene oxide). Makromolekulare Chemie 1988; 189(12): 2885–2892.

Merino

Brauge

Caminade

. Synthesis and characterization of linear, hyperbranched, and dendrimer-like polymers constituted of the same repeating unit. Chemistry 2001; 7(14): 3095–3105.

10.

Tomalia

Baker

Dewald

. Dendritic macromolecules: synthesis of starburst dendrimers. Macromolecules 1986; 19(9): 2466–2468.

11.

Morikawa

Kakimoto

Imai

. Convergent synthesis of siloxane starburst dendrons and dendrimers via hydrosilylation. Macromolecules 1992; 25(12): 3247–3253.

12.

Davaran

Omidi

Rashidi

. Preparation and in vitro evaluation of linear and star-branched PLGA nanoparticles for insulin delivery. J Bioact Compat Polym 2008; 23(2): 115–131.

13.

Chang

H-T

Frechet

JMJ

. Proton-transfer polymerization: a new approach to hyperbranched polymers. J Am Chem Soc 1999; 121(10): 2313–2314.

14.

Gong

Frechet

JMJ

. Proton transfer polymerization in the preparation of hyperbranched polyesters with epoxide chain-ends and internal hydroxyl functionalities. Macromolecules 2000; 33(14): 4997–4999.

15.

Suzuki

Saegusa

. Multibranching polymerization: palladium-catalyzed ring-opening polymerization of cyclic carbamate to produce hyperbranched dendritic polyamine. Macromolecules 1992; 25(25): 7071–7072.

16.

Cheng

Yuan

Sun

. Effect of degree of branching on the self-assembly of amphiphilic hyperbranched multiarm copolymers. Macromolecules 2010; 43(2): 1143–1147.

17.

Bednarek

Biedron

Helinski

. Branched polyether with multiple primary hydroxyl groups: polymerization of 3-ethyl-3-hydroxymethyloxetane. Macromol Rapid Commun 1999; 20(7): 369–372.

18.

Bednarek

Kubisa

Penczek

. Multihydroxyl branched polyethers. 2. Mechanistic aspects of cationic polymerization of 3-ethyl-3-(hydroxymethyl)oxetane. Macromolecules 2001; 34(15): 5112–5119.

19.

Mai

Zhou

Yan

. Effect of reaction temperature on degree of branching in cationic polymerization of 3-ethyl-3-(hydroxymethyl)oxetane. Macromolecules 2003; 36(25): 9667–9669.

20.

Wilms

Stiriba

S-E

Frey

. Hyperbranched polyglycerols: from the controlled synthesis of biocompatible polyether polyols to multipurpose applications. Acc Chem Res 2009; 43(1): 129–141.

21.

Tziveleka

L-A

Psarra

A-MG

Tsiourvas

. Synthesis and evaluation of functional hyperbranched polyether polyols as prospected gene carriers. Int J Pharm 2008; 356(1–2): 314–324.

22.

Kainthan

Hester

Levin

. In vitro biological evaluation of high molecular weight hyperbranched polyglycerols. Biomaterials 2007; 28(31): 4581–4590.

23.

Sarkar

Yang

. Encapsulation and extended release of anti-cancer anastrozole by stealth nanoparticles. Drug Deliv 2008; 15(5): 343–346.

24.

Yang

Lopina

. Stealth dendrimers for antiarrhythmic quinidine delivery. J Mater Sci: Mater Med 2007; 18(10): 2061–2065.

25.

Yang

Lopina

DiPersio

. Stealth dendrimers for drug delivery: correlation between PEGylation, cytocompatibility, and drug payload. J Mater Sci: Mater Med 2008; 19(5): 1991–1997.

26.

Veronese

Caliceti

Schiavon

. Branched and linear poly(ethylene glycol): influence of the polymer structure on enzymological, pharmacokinetic, and immunological properties of protein conjugates. J Bioact Compat Polym 1997; 12(3): 196–207.

27.

Wan

Kou

. The characters of self-assembly core/shell nanoparticles of amphiphilic hyperbranched polyethers as drug carriers. J Nanopart Res 2008; 10(3): 437–448.

28.

Yang

Morris

Lopina

. Polyethylene glycol-polyamidoamine dendritic micelle as solubility enhancer and the effect of the length of polyethylene glycol arms on the solubility of pyrene in water. J Colloid Interface Sci 2004; 273(1): 148–154.

29.

Yeudall

Crawford

Ensley

. MTS1/CDK4I is altered in cell lines derived from primary and metastatic oral squamous cell carcinoma. Carcinogenesis 1994; 15(12): 2683–2686.

30.

Cheng

. Potential of poly(amidoamine) dendrimers as drug carriers of camptothecin based on encapsulation studies. Eur J Med Chem 2008; 43(8): 1791–1795.

31.

Kailasan

Yuan

Yang

. Synthesis and characterization of thermoresponsive polyamidoamine-polyethylene glycol-poly (D,i-lactide) (PAMAM-PEG-PDLLA) core–shell nanoparticles. Acta Biomater 2010; 6(3): 1131–1139.

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Poly(ethylene glycol)-armed hyperbranched polyoxetanes for anticancer drug delivery

Abstract

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