Poly(N-vinylpyrrolidone)-block-poly(D,L-lactide) as a new polymeric solubilizer for hydrophobic anticancer drugs: in vitro and in vivo evaluation
- PMID: 15342183
- DOI: 10.1016/j.jconrel.2004.06.018
Poly(N-vinylpyrrolidone)-block-poly(D,L-lactide) as a new polymeric solubilizer for hydrophobic anticancer drugs: in vitro and in vivo evaluation
Abstract
The majority of novel anticancer drugs developed to date are intended for parenteral administration. Paradoxically, most of these drugs are water-insoluble, delaying their clinical development. A common approach to confering water solubility to drugs is to use amphiphilic, solubilizing agents, such as polyethoxylated castor oil (e.g., Cremophor EL, CrmEL). However, these vehicles are themselves associated with a number of pharmacokinetic and pharmaceutical concerns. The present work is aimed at evaluating a novel polymeric solubilizer for anticancer drugs, i.e., poly(N-vinylpyrrolidone)-block-poly(D,L-lactide) (PVP-b-PDLLA). This copolymer self-assembles in water to yield polymeric micelles (PM) that efficiently solubilize anticancer drugs, such as paclitaxel (PTX), docetaxel (DCTX), teniposide (TEN) and etoposide (ETO). A PM-PTX formulation was evaluated, both, in vitro on three different cancer cell lines and in vivo for its safety, pharmacokinetics, biodistribution and antitumor activity. In vitro, cytotoxicity studies revealed that the drug-loaded PM formulation was equipotent to the commercial PTX formulation (Taxol). In the absence of drug, PVP-b-PDLLA with 37% DLLA content was less cytotoxic than CrmEL. In vivo, acute toxicity was assessed in mice after a single injection of escalating dose levels of formulated PTX. PM-PTX was well tolerated and the maximum tolerated dose (MTD) was not reached even at 100 mg/kg, whereas the MTD of Taxol was established at 20 mg/kg. At 60 mg/kg, PM-PTX demonstrated greater in vivo antitumor activity than Taxol injected at its MTD. Finally, it was shown in mice and rabbits that the areas under the plasma concentration-time curves were inversely related to PM drug loading.
Similar articles
-
Novel self-assembling PEG-p-(CL-co-TMC) polymeric micelles as safe and effective delivery system for paclitaxel.Eur J Pharm Biopharm. 2009 Oct;73(2):230-8. doi: 10.1016/j.ejpb.2009.06.015. Epub 2009 Jul 3. Eur J Pharm Biopharm. 2009. PMID: 19577643
-
Incorporation and in vitro release of doxorubicin in thermally sensitive micelles made from poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide)-b-poly(D,L-lactide-co-glycolide) with varying compositions.Biomaterials. 2005 Aug;26(24):5064-74. doi: 10.1016/j.biomaterials.2005.01.030. Biomaterials. 2005. PMID: 15769542
-
Thermosensitive and biodegradable polymeric micelles for paclitaxel delivery.J Control Release. 2005 Mar 21;103(2):341-53. doi: 10.1016/j.jconrel.2004.12.009. J Control Release. 2005. PMID: 15763618
-
Micelles from lipid derivatives of water-soluble polymers as delivery systems for poorly soluble drugs.Adv Drug Deliv Rev. 2004 May 7;56(9):1273-89. doi: 10.1016/j.addr.2003.12.004. Adv Drug Deliv Rev. 2004. PMID: 15109769 Review.
-
Novel Taxol formulations: Taxol-containing liposomes.J Natl Cancer Inst Monogr. 1993;(15):69-78. J Natl Cancer Inst Monogr. 1993. PMID: 7912532 Review.
Cited by
-
Antitumor effect of a polypeptide fraction from Arca subcrenata in vitro and in vivo.Mar Drugs. 2012 Dec;10(12):2782-94. doi: 10.3390/md10122782. Mar Drugs. 2012. PMID: 23342393 Free PMC article.
-
Development of a Rapid and Precise Reversed-phase High-performance Liquid Chromatography Method for Analysis of Docetaxel in Rat Plasma: Application in Single-dose Pharmacokinetic Studies of Folate-targeted Micelles Containing Docetaxel.Adv Biomed Res. 2018 May 23;7:76. doi: 10.4103/abr.abr_251_16. eCollection 2018. Adv Biomed Res. 2018. PMID: 29930916 Free PMC article.
-
Micellar delivery of flutamide via milk protein nanovehicles enhances its anti-tumor efficacy in androgen-dependent prostate cancer rat model.Pharm Res. 2013 Oct;30(10):2654-63. doi: 10.1007/s11095-013-1091-7. Epub 2013 Jun 6. Pharm Res. 2013. PMID: 23739989
-
Navigare necessere est. Improved navigation would help to solve two crucial problems in modern drug therapy: toxicity and precise delivery.EMBO Rep. 2005 Aug;6(8):695-700. doi: 10.1038/sj.embor.7400484. EMBO Rep. 2005. PMID: 16065058 Free PMC article.
-
Nanoparticle administration method in cell culture alters particle-cell interaction.Sci Rep. 2019 Jan 29;9(1):900. doi: 10.1038/s41598-018-36954-4. Sci Rep. 2019. PMID: 30696847 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources