Polymeric Micelles of Modified Chitosan Block Copolymer as Nanocarrier for Delivery of Paclitaxel

Author(s): V. Lather, V. Saini, D. Pandita*.

Journal Name: Current Nanomedicine
Formerly Recent Patents on Nanomedicine

Volume 9 , Issue 1 , 2019

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Abstract:

Background: Polymeric micelles are being used as successful nanocarriers for the delivery of diverse drug molecules due to properties like solubilization, selective targeting, P-glycoprotein inhibition, altered drug internalization route and subcellular localization etc.

Objective: The present investigation was planned to prepare and characterize novel polymeric micelles derived from self assembly of amphiphilic chitosan-bile salt derivative (CS-mPEG-DA) as nanocarrier and evaluate their potential in delivery of an anticancer drug, paclitaxel.

Method: Paclitaxel, a diterpenoid compound, useful in clinical treatment of several solid tumors such as ovarian cancer, breast cancer and lung cancer suffers from limitations like low aqueous solubility and bioavailability and subsequently was used as the model drug.

Results: Paclitaxel was successfully incorporated into polymeric micelles using dialysis and emulsion method with encapsulation efficiency up to 95% having particle size in nanometer range (<200 nm). Paclitaxel loaded micelles were found to release the drug in a sustained manner up to 96 h in PBS containing 0.1% (w/v) tween 80 at 37°C. The micelles powders subjected to stability studies for a period of 90 days were found to be stable at 4 ± 2°C with respect to particle size and drug content. In vivo cytotoxicity assay confirmed that paclitaxel encapsulated in polymeric micelles showed higher cytotoxicity against cultured MCF-7 breast cancer cells than paclitaxel alone.

Conclusion: Polymeric micellar systems derived from copolymerization of chitosan exhibit a great potential in successful delivery of poorly water soluble or low bioavailable drugs like paclitaxel.

Keywords: Polymeric micelles, amphiphilic, self assembly, chitosan, paclitaxel, copolymer.

[1]
Lu Y, Park K. Polymeric micelles and alternative nanonized delivery vehicles for poorly soluble drugs. Int J Pharm 2013; 453: 198-214.
[2]
Li Y, Xu X, Shen Y, Qian C, Lu F, Guo S. Preparation and evaluation of copolymeric micelles with high paclitaxel contents and sustained drug release. Colloids Surf A Physicochem Eng Asp 2013; 429: 12-8.
[3]
Zhang L, He Y, Ma G, Song C, Sun H. Paclitaxel-loaded polymeric micelles based on poly(ɛ-capro-lactone)-poly(ethylene glycol)-poly(ɛ-caprolactone) triblock copolymers: in vitro and in vivo evaluation. Nanomedicine 2012; 8: 925-34.
[4]
Cui MY, Dong Z, Cai H, et al. Folate-targeted polymeric micelles loaded with superparamagnetic iron oxide as a contrast agent for magnetic resonance imaging of a human tongue cancer cell line. Mol Med Rep 2017. [Epub ahead of print].
[5]
Dai Y, Wang S, Shi W, Lang M. pH-responsive carboxymethyl chitosan-derived micelles as apatinib carriers for effective anti-angiogenesis activity: Preparation and in vitro evaluation. Carbohydr Polym 2017; 176: 107-16.
[6]
Ruttala HB, Chitrapriya N, Kaliraj K, et al. Facile construction of bioreducible crosslinked polypeptide micelles for enhanced cancer combination therapy. Acta Biomater 2017. [Epub ahead of print].
[7]
Zhang J, Zhao X, Chen Q, Yin X, Xin X, Li K, et al. Systematic evaluation multifunctional paclitaxel-loaded polymeric mixed micelles as a potential anticancer remedy to overcome multidrug resistance. Acta Biomater 2017; 50: 381-95.
[8]
Qi D, Gong F, Teng X, Ma M, Wen H, Yuan W, et al. Design and evaluation of mPEG-PLA micelles functionalized with drug-interactive domains as improved drug carriers for docetaxel delivery. J Biomater Sci Polym Ed 2017; 28: 1538-55.
[9]
Kong XY, Li XY, Wang XH, Liu TT, Gu YC, Buo G, et al. Synthesis and characterization of a novel MPEG–chitosan diblock copolymer and self-assembly of nanoparticles. Carbohydr Polym 2010; 79: 170-5.
[10]
Pan Z, Gao Y, Heng L, Liu Y, et al. Amphiphilic N-(2,3-dihydroxypropyl)-chitosan-cholic acid micelles for paclitaxel delivery. Carbohydr Polym 2013; 94: 394-9.
[11]
Wang F, Zhang D, Duan C, et al. Preparation and characterizations of a novel deoxycholic acid–O-carboxymethylated chitosan–folic acid conjugates and self-aggregates. Carbohydr Polym 2011; 84: 1192-200.
[12]
Silva DS, Almeida A, Prezotti F. Synthesis and characterization of 3,6-O,O′- dimyristoyl chitosan micelles for oral delivery of paclitaxel. Colloids Surf B Biointerfaces 2017; 152: 220-8.
[13]
Almeida A, Silva D, Gonçalves V, Sarmento B. Synthesis and characterization of chitosan-grafted-polycaprolactone micelles for modulate intestinal paclitaxel delivery. Drug Deliv Transl Res 2017; 8(2): 387-97.
[14]
Chae SY, Son S, Lee M, Jang MK, Nah JW. Deoxycholic acid-conjugated chitosan oligosaccharide nanoparticles for efficient gene carrier. J Control Release 2005; 109: 330-44.
[15]
Ngawhirunpat T, Wonglertnirant N, Opanasopit P, et al. Incorporation methods for cholic acid chitosan-g-mPEG self-assembly micellar system containing camptothecin. Colloids Surf B Biointerfaces 2009; 74: 253-9.
[16]
Pandita D, Ahuja A, Lather V, et al. Development of lipid-based nanoparticles for enhancing the oral bioavailability of paclitaxel. AAPS PharmSciTech 2011; 12: 712-22.
[17]
Xu J, Zhang X, Chen Y, et al. Improved micellar formulation for enhanced delivery for paclitaxel. Mol Pharm 2017; 14: 31-41.
[18]
Pandita D, Ahuja A, Velpandian T, Lather V, Dutta T, Khar RK. Characterization and in vitro assessment of paclitaxel loaded lipid nanoparticles formulated using modified solvent injection technique. Pharmazie 2009; 64: 301-10.
[19]
Teeranachaideekul V, Souto EB, Junyaprasert VB, Muller RH. Cetyl palmitate-based NLC for topical delivery of Coenzyme Q(10) - development, physicochemical characterization and in vitro release studies. Eur J Pharm Biopharm 2007; 67: 141-8.
[20]
Wang F, Chen Y, Zhang D, et al. Folate-mediated targeted and intracellular delivery of paclitaxel using a novel deoxycholic acid-O-carboxymethylated chitosan-folic acid micelles. Int J Nanomed 2012; 7: 325-37.
[21]
Zhang Y, Huo M, Zhou J, Yu D, Wu Y. Potential of amphiphilically modified low molecular weight chitosan as a novel carrier for hydrophobic anticancer drug: Synthesis, characterization, micellization and cytotoxicity evaluation. Carbohydr Polym 2009; 77: 231-8.
[22]
Francis MF, Piredda M, Winnik FM. Solubilization of poorly water soluble drugs in micelles of hydrophobically modified hydroxypropylcellulose copolymers. J Control Rel 2003; 93: 59-68.
[23]
M JF and P L. Apoptotic efficacy of biogenic silver nanoparticles on human breast cancer MCF-7 cell lines. Prog Biomater 2015; 4: 113-21.
[24]
Soni P, Kaur J, Tikoo K. Dual drug-loaded paclitaxel–thymoquinone nanoparticles for effective breast cancer therapy. J Nanopart Res 2015; 17: 18.


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Article Details

VOLUME: 9
ISSUE: 1
Year: 2019
Page: [86 - 96]
Pages: 11
DOI: 10.2174/2468187308666180426120050
Price: $58

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