Optimization of parameters for preparation of docetaxel-loaded PLGA nanoparticles by nanoprecipitation method

Abstract

The purpose of this study was to develop docetaxel-poly (lactide-co-glycolide) (PLGA) loaded nanoparticles by using nanoprecipitation method and optimize the relative parameters to obtain nanoparticles with higher encapsulation efficiency and smaller size. The physicochemical characteristics of nanoparticles were studied. The optimized parameters were as follows: the oil phase was mixture of acetone and ethanol, concentration of tocopheryl polyethylene glycol succinate (TPGS) was 0.2%, the ratio of oil phase to water phase was 1:5, and the theoretical drug concentration was 5%. The optimized nanoparticles were spherical with size between 130 and 150 nm. The encapsulation efficiency was (40.83±2.1)%. The in vitro release exhibited biphasic pattern. The results indicate that docetaxel-PLGA nanoparticles were successfully fabricated and may be used as the novel vehicles for docetaxel, which would replace Taxotere® and play great roles in future.

Keywords

docetaxel / nanoparticles / optimization / poly (lactide-co-glycolide) / cancer

References

[1] PetrioliR, PozzessereD, MessineseS, et al.. Weekly low-dose docetaxel in advanced non-small cell lung cancer previously treated with two chemotherapy regimens. Lung Cancer, 2003, 39(1): 85-89

[2] ColemanRE, HowellA, EggletonSP, et al.. Phase II study of docetaxel in patients with liver metastases from breast cancer. Ann Oncol, 2000, 11(5): 541-546

[3] GlissonBS, MurphyBA, FrenetteG, et al.. Phase II trial of docetaxel and cisplatin combination chemotherapy in patients with squamous cell carcinoma of the head and neck. J Clin Oncol, 2002, 20(6): 1593-1599

[4] RowinskyEK. The development and clinical utility of the taxane class of antimicrotubule chemotherapy agents. Annu Rev Med, 1997, 48: 353-374

[5] WeissRB, DonehowerRC, WiernikPH, et al.. Hypersensitivity reactions from Taxol. J Clin Oncol, 1990, 8(7): 1263-1268

[6] ChuCY, YangCH, YangCY, et al.. Fixed erythrodysaesthesia plaque due to intravenous injection of docetaxel. Br J Dermatol, 2000, 142(4): 808-811

[7] LavelleF, BisseryMC, CombeauC, et al.. Preclinical evaluation of docetaxel (Taxotere). Semin Oncol, 1995, 22(2Suppl4): 3-16

[8] XuZ, ChenL, GuW, et al.. The performance of docetaxel-loaded solid lipid nanoparticles targeted to hepatocellular carcinoma. Biomaterials, 2009, 30(2): 226-232

[9] FarokhzadOC, LangerR. Impact of nanotechnology on drug delivery. ACS Nano, 2009, 3(1): 16-20

[10] HaleyB, FrenkelE. Nanoparticles for drug delivery in cancer treatment. Urol Oncol, 2008, 26(1): 57-64

[11] SahaRN, VasanthakumarS, BendeG, et al.. Nanoparticulate drug delivery systems for cancer chemotherapy. Mol Membr Biol, 2010, 27(7): 215-231

[12] BennisS, ChapeyC, CouvreurP, et al.. Enhanced cytotoxicity of doxorubicin encapsulated in polyisohexylcy-anoacrylate nanospheres against multidrug-resistant cells in culture. Eur J Cancer, 1994, 30A(1): 89-93

[13] MagenheimB, BenitaS. Nanoparticle characterization: a comprehensive physicochemical approach. STP Pharm Sci, 1991, 1: 221-241

[14] ShiveMS, AndersonJM. Biodegradation and biocompatibility of PLA and PLGA microspheres. Adv Drug Deliv Rev, 1997, 28(1): 5-24

[15] GanCW, FengSS. Transferrin-conjugated nanoparticles of poly (lactide)-D-alpha-tocopheryl polyethylene glycol succinate diblock copolymer for targeted drug delivery across the blood-brain barrier. Biomaterials, 2010, 31(30): 7748-7757

[16] ZhangZ, MeiL, FengSS. Vitamin E D-alpha-tocopheryl polyethylene glycol 1000 succinate-based nanomedicine. Nanomedicine (Lond), 2012, 7(11): 1645-1647

[17] SaxenaV, HussainMD. Inhibition of P-glycoprotein by D-alpha-tocopheryl polyethylene glycol 1000 succinate^(TPGS). J Biomed Nanotechnol, 2013, 9(7): 1146-1154

[18] VarmaMV, PanchagnulaR. Enhanced oral paclitaxel absorption with vitamin E-TPGS: effect on solubility and permeability in vitro, in situ and in vivo. Eur J Pharm Sci, 2005, 25(4–5): 445-453

[19] CollnotEM, BaldesC, SchaeferUF. Vitamin E TPGS p-glycoprotein inhibition mechanism: influence on conformational flexibility, intracellular ATP levels, and role of time and site of access. Mol Pharm, 2010, 7(3): 642-651

[20] ZhangZ, LeeSH, GanCW, et al.. In vitro and in vivo investigation on PLA-TPGS nanoparticles for controlled and sustained small molecule chemotherapy. Pharm Res, 2008, 25(8): 1925-1935

[21] PrashantC, DipakM, YangCT, et al.. Superparamagnetic iron oxide-loaded poly (lactic acid)-D-alpha-tocopherol polyethylene glycol 1000 succinate copolymer nanoparticles as MRI contrast agent. Biomaterials, 2010, 31(21): 5588-5597

[22] WinKY, FengSS. In vitro and in vivo studies on vitamin E TPGS-emulsified poly(D,L-lacticcoglycolid acid) nanoparticles for paclitaxel formulation. Biomaterials, 2006, 27(10): 2285-2291

[23] BarichelloJM, MorishitaM, TakayamaK, et al.. Encapsulation of hydrophilic and lipophilic drugs in PLGA nanoparticles by the nanoprecipitation method. Drug Dev Ind Pharm, 1999, 25(4): 471-476

[24] DongY, FengSS. Methoxyl poly(ethylene glycol)poly-(lactide) (MPEG-PLA) nanoparticles for controlled delivery of anticancer drugs. Biomaterials, 2004, 25(14): 2843-2849

[25] ZhangZ, FengSS. Nanoparticles of poly (lactide)/Vitamin E TPGS copolymer for cancer chemotherapy: synthesis, formulation, characterization and in vitro drug release. Biomaterials, 2006, 27(2): 262-270

[26] MuL, FengSS. A novel controlled release formulation for the anticancer drug paclitaxel^(Taxol): PLGA nanoparticles containing vitamin E TPGS. J Control Release, 2003, 86(1): 33-48

[27] MuL, FengSS. Vitamin E TPGS used as emulsifier in the solvent evaporation/extraction technique for fabrication of polymeric nanospheres for controlled release of paclitaxel (Taxol). J Control Release, 2002, 80(1–3): 129-144

[28] KakranM, SahooNG, AntipinaMN, et al.. Modified supercritical antisolvent method with enhanced mass transfer to fabricate drug nanoparticles. Mater Sci Eng C Mater Biol Appl, 2013, 33(5): 2864-2870

[29] SongX, ZhaoY, HouS, et al.. Dual agents loaded PLGA nanoparticles: Systematic study of particle size and drug entrapment efficiency. Eur J Pharm Biopharm, 2008, 69(2): 445-453

[30] LamprechtA, UbrichN, Hombreiro PérezM, et al.. Influences of process parameters on nanoparticle preparation performed by a double emission pressure homogenization technique. Int J Pharm, 2000, 196(2): 177-182

[31] ZhaoL, FengSS. Enhanced oral bioavailability of paclitaxel formulated in vitamin E-TPGS emulsified nanopart icles of biodegradable polymers: in vitro and in vivo studies. J Pharm Sci, 2010, 99(8): 3552-3560

[32] ZhangZ, FengSS. Nanoparticles of poly (lacide)/vitamin E TPGS copolymer for cancer chemotherapy: synthesis, formulation, characterization and in vitro drug release. Biomaterials, 2006, 27(2): 262-270