Evaluation of Paclitaxel Nanocrystals In Vitro and In Vivo

Wanqing Li; Zhiguo Li; Lisha Wei; Aiping Zheng

doi:10.1055/s-0043-119461

Drug Research, Table of Contents

Drug Res (Stuttg) 2018; 68(04): 205-212
DOI: 10.1055/s-0043-119461

Original Article

Evaluation of Paclitaxel Nanocrystals In Vitro and In Vivo

Wanqing Li

¹School of Basic Medicine, Beijing University of Chinese Medicine, Beijing, P.R.China

,

Zhiguo Li

²State Key Laboratory of Toxicology and Medical Countermeasures Department of Pharmaceutics, Beijing Institute of Pharmacology and Toxicology, Beijing, P.R.China

,

Lisha Wei

²State Key Laboratory of Toxicology and Medical Countermeasures Department of Pharmaceutics, Beijing Institute of Pharmacology and Toxicology, Beijing, P.R.China

,

Aiping Zheng

²State Key Laboratory of Toxicology and Medical Countermeasures Department of Pharmaceutics, Beijing Institute of Pharmacology and Toxicology, Beijing, P.R.China

› Author Affiliations

Abstract

We created a novel paclitaxel (PTX) nanoparticle drug delivery system and compared this to acommercial injection preparation to evaluate the antitumor effects for both formulations in vivo and in vitro.PTXnanocrystals were 194.9 nm with potential of −29.6 mV. Cytotoxicity tests indicated that both formulations had similar effects and cytotoxicity was dose- and time-dependent.Pharmacodynamics indicated that the drug concentration at the tumor was greater with PTX nanocrystals compared to commercial injection (P<0.01) and that drug accumulated more and for a longer duration. In vivo antitumor evaluation indicated significant antitumor effects and low toxicity of PTX nanocrystals. Moreover, bioimaging indicated that the PTX retention time in MCF-7-bearing mice was longer, especially at the tumor site, and this high drug concentration was maintained for a long time.Overall, PTX nanocrystalsare feasible and superior to traditional injection formulation chemotherapy.

Key words

paclitaxel - nanocrystals - MCF-7 - pharmacodynamics - bioimaging

Full Text

References

References
1 Lipinski CA. Poor aqueous solubility – an industry wide problem in ADME screening. Am Pharm Rev 2002; 5: 82
2 Heimbach T, Fleisher D, Kaddoumi A. Overcoming poor aqueous solubility of drugs for oral delivery. pp 157-215 Springer; New York: 2007
3 Chen H, Khemtong C, Yang X. et al. Nanonization strategies for poorly water-soluble drugs. Drug Discovery Today 2011; 16: 354-360
4 Ali A, Ansari V A, Ahmad U. et al. Nanoemulsion: An advanced vehicle for efficient drug delivery. Drug Res 2017; 67: 1-15
5 Amidon GL, Lennernäs H, Shah V P. et al. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharmaceutical Research 1995; 12: 413-420
6 Spencer CM, Faulds D. Paclitaxel. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in the treatment of cancer. Drugs 1994; 48: 794
7 Guo XY, Wang P, Du QG. et al. Paclitaxel and gemcitabine combinational drug-loaded mucoadhesive delivery system in the treatment of colon cancers. Drug Research 2015; 65: 199
8 Varma MV, Sateesh K, Panchagnula R. Functional role of P-glycoprotein in limiting intestinal absorption of drugs: contribution of passive permeability to P-glycoprotein mediated efflux transport. Molecular Pharmaceutics 2005; 2: 12
9 Gelderblom H, Verweij J, Nooter K. et al. Cremophor EL: the drawbacks and advantages of vehicle selection for drug formulation. European Journal of Cancer 2001; 37: 1590-1598
10 Nyman DW, Campbell KJ, Hersh E. et al. Phase I and pharmacokinetics trial of ABI-007, a novel nanoparticle formulation of paclitaxel in patients with advanced nonhematologic malignancies. Journal of Clinical Oncology Official Journal of the American Society of Clinical Oncology 2005; 23: 7785-7793
11 Hennenfent KL, Govindan R. Novel formulations of taxanes: a review. Old wine in a new bottle?. Annals of Oncology 2006; 17: 735-749
12 Sznitowska M, Klunder M. M, Paclitaxel solubility in aqueous dispersions and mixed micellar solutions of lecithin. Chemical & Pharmaceutical Bulletin 2008; 56: 70-74
13 Dr KR, Dr BG, Mauro Ferrari Prof. et al. Nanomedicine—challenge and perspectives. Angewandte Chemie 2009; 48: 872-897
14 Naseri N, Zakerimilani P, Hamishehkar H. et al. Development, in vitro characterization, antitumor and aerosol performance evaluation of respirable prepared by self-nanoemulsification method. Drug Res 2017; 67: 343-348
15 Jens-Uwe AH, Junghanns RHM. Nanocrystal technology, drug delivery and clinical applications. International Journal of Nanomedicine 2008; 3: 295-309
16 Shegokar R, Müller RH. Nanocrystals: industrially feasible multifunctional formulation technology for poorly soluble actives. International Journal of Pharmaceutics 2010; 399: 129-139
17 Chen H, Wan J, Wang Y. et al. A facile nanoaggregation strategy for oral delivery of hydrophobic drugs by utilizing acid-base neutralization reactions. Nanotechnology 2008; 19: 375104
18 Zhang H, Hollis CP, Zhang Q. et al. Preparation and antitumor study of camptothecin nanocrystals. International Journal of Pharmaceutics 2011; 415: 293
19 Han J, Talorete TP, Yamada P. et al. Anti-proliferative and apoptotic effects of oleuropein and hydroxytyrosol on human breast cancer MCF-7 cells. Cytotechnology 2009; 59: 45-53
20 Ansari KA, Torne SJ, Vavia PR. et al. Paclitaxel loaded nanosponges: in-vitro characterization and cytotoxicity study on MCF-7 cell line culture. Current Drug Delivery 2011; 8: 194-202
21 Yang T, Choi MK, Cui FD. et al. Antitumor effect of paclitaxel-loaded PEGylated immunoliposomes against human breast cancer cells. Pharmaceutical Research 2007; 24: 2402
22 Jarzyna PA, Deddens LH, Kann BH. et al. Tumor angiogenesis phenotyping by nanoparticle-facilitated magnetic resonance and near-infrared fluorescence molecular imaging 1. Neoplasia 2012; 14: 964-973
23 Hollis CP, Weiss HL, Leggas M. et al. Biodistribution and bioimaging studies of hybrid paclitaxel nanocrystals: lessons learned of the EPR effect and image-guided drug delivery. Journal of Controlled Release Official Journal of the Controlled Release Society 2013; 172: 12-21
24 Liu F, Park JY, Zhang Y. et al. Targeted cancer therapy with novel high drug-loading nanocrystals. Journal of Pharmaceutical Sciences 2010; 99: 3542-3551
25 Gaumet M, Vargas A, Gurny R. et al. Nanoparticles for drug delivery: the need for precision in reporting particle size parameters. European Journal of Pharmaceutics & Biopharmaceutics 2008; 69: 1-9