Login Register Cart 0
Generic placeholder image

Current Drug Delivery

Editor-in-Chief

ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Nanofibrous Polydioxanone Depots for Prolonged Intraperitoneal Paclitaxel Delivery

Author(s): Smrithi Padmakumar and Deepthy Menon*

Volume 16, Issue 7, 2019

Page: [654 - 662] Pages: 9

DOI: 10.2174/1567201816666190816102949

Price: $65

Abstract

Background: Prolonged chemodrug delivery to the tumor site is a prerequisite to maintaining its localised therapeutic concentrations for effective treatment of malignant solid tumors.

Objective: The current study aims to develop implantable polymeric depots through conventional electrospinning for sustained drug delivery, specifically to the peritoneum.

Methods: Non-woven electrospun mats were fabricated by simple electrospinning of Polydioxanone solution loaded with the chemodrug, Paclitaxel. The implants were subjected to the analysis of morphology, mechanical properties, degradation and drug release in phosphate buffer and patient-derived peritoneal drain fluid samples. In vivo studies were conducted by surgical knotting of these implants to the peritoneal wall of healthy mice.

Results: Non-woven electrospun mats with a thickness of 0.65±0.07 mm, weighing ~ 20 mg were fabricated by electrospinning 15 w/v% polymer loaded with 10 w/w% drug. These implants possessing good mechanical integrity showed a drug entrapment efficiency of 87.82±2.54 %. In vitro drug release studies in phosphate buffer showed a sustained profile for ~4 weeks with a burst of 10 % of total drug content, whereas this amounted to >60% in patient samples. Mice implanted with these depots remained healthy during the study period. The biphasic drug release profile obtained in vivo showed a slow trend, with peritoneal lavage and tissues retaining good drug concentrations for a sustained period.

Conclusion: The results indicate that non-woven electrospun mats developed from biodegradable Polydioxanone polymer can serve as ideal candidates for easily implantable drug depots to address the challenges of peritoneal metastasis in ovarian cancer.

Keywords: Nanofibres, polydioxanone, paclitaxel, electrospinning, drug delivery, prolonged drug release.

« Previous Next »
Graphical Abstract

[1]
Fung, L.K.; Saltzman, W.M. Polymeric Implants for Cancer Chemotherapy, 1997, 26, 209-230.
[2]
Jang, S.H.; Wientjes, M.G.; Lu, D.; Au, J.L. Drug delivery and transport to solid tumors. Pharm. Res., 2003, 20(9), 1337-1350.
[http://dx.doi.org/10.1023/A:1025785505977] [PMID: 14567626]
[3]
Weinberg, B.D.; Blanco, E.; Gao, J. Polymer implants for intratumoral drug delivery and cancer therapy. J. Pharm. Sci., 2008, 97(5), 1681-1702.
[http://dx.doi.org/10.1002/jps.21038] [PMID: 17847077]
[4]
Wolinsky, J.; Colson, Y.; Grinstaff, M. Local drug delivery strategies for cancer treatment: Gels, nanoparticles, polymeric films, rods, and wafers public access. J. Control. Release, 2012, 159(1), 1-34.
[http://dx.doi.org/10.1016/j.jconrel.2011.11.031] [PMID: 22482835]
[5]
Yang, W.; Pierstorff, E. Reservoir-based polymer. Drug Deliv. Syst., 2015.
[6]
De Souza, R.; Zahedi, P.; Allen, C.J.; Piquette-miller, M. Polymeric drug delivery systems for localized cancer chemotherapy. Durg Deliv., 2010, 17(6), 365-375.
[7]
Ramazani, F.; Van Nostrum, C.F.; Storm, G.; Kiessling, F.; Lammers, T.; Hennink, W.E.; Kok, R.J. Locoregional cancer therapy using polymer-based drug depots. Drug Discovery Today; Elsevier Ltd., 2016, pp. 640-647.
[8]
De Smet, L.; Ceelen, W.; Remon, J.P.; Vervaet, C. Optimization of drug delivery systems for intraperitoneal therapy to extend the residence time of the chemotherapeutic agent. Sci. World J., 2013.2013720858
[http://dx.doi.org/10.1155/2013/720858] [PMID: 23589707]
[9]
Padmakumar, S.; Parayath, N.; Leslie, F.; Nair, S.V.; Menon, D.; Amiji, M.M. Intraperitoneal chemotherapy for ovarian cancer using sustained-release implantable devices. Expert Opin. Drug Deliv., 2018, 15(5), 481-494.
[http://dx.doi.org/10.1080/17425247.2018.1446938] [PMID: 29488406]
[10]
Dedrick, R.L.; Myers, C.E.; Bungay, P.M.; DeVita, V.T., Jr Pharmacokinetic rationale for peritoneal drug administration in the treatment of ovarian cancer. Cancer Treat. Rep., 1978, 62(1), 1-11.
[PMID: 626987]
[11]
Amoozgar, Z.; Wang, L.; Brandstoetter, T.; Wallis, S.S.; Wilson, E.M.; Goldberg, M.S. Dual-layer surface coating of PLGA-based nanoparticles provides slow-release drug delivery to achieve metronomic therapy in a paclitaxel-resistant murine ovarian cancer model. Biomacromolecules, 2014, 15(11), 4187-4194.
[http://dx.doi.org/10.1021/bm5011933] [PMID: 25251833]
[12]
Kohane, D.S.; Tse, J.Y.; Yeo, Y.; Padera, R.; Shubina, M.; Langer, R. Biodegradable polymeric microspheres and nanospheres for drug delivery in the peritoneum. J. Biomed. Mater. Res. A, 2006, 77(2), 351-361.
[http://dx.doi.org/10.1002/jbm.a.30654] [PMID: 16425240]
[13]
Dhanikula, A.B.; Singh, D.R.; Panchagnula, R. In vivo pharmacokinetic and tissue distribution studies in mice of alternative formulations for local and systemic delivery of Paclitaxel: Gel, film, prodrug, liposomes and micelles. Curr. Drug Deliv., 2005, 2(1), 35-44.
[http://dx.doi.org/10.2174/1567201052772852] [PMID: 16305406]
[14]
Bajaj, G.; Kim, M.R.; Mohammed, S.I.; Yeo, Y. Hyaluronic acid-based hydrogel for regional delivery of paclitaxel to intraperitoneal tumors. J. Control. Release, 2012, 158(3), 386-392.
[http://dx.doi.org/10.1016/j.jconrel.2011.12.001] [PMID: 22178261]
[15]
Ho, E.A.; Vassileva, V.; Allen, C.; Piquette-Miller, M. In vitro and in vivo characterization of a novel biocompatible polymer-lipid implant system for the sustained delivery of paclitaxel. J. Control. Release, 2005, 104(1), 181-191.
[http://dx.doi.org/10.1016/j.jconrel.2005.02.008] [PMID: 15866344]
[16]
Ye, H.; Tanenbaum, L.M.; Na, Y.J.; Mantzavinou, A.; Fulci, G.; Del Carmen, M.G.; Birrer, M.J.; Cima, M.J. Sustained, low-dose intraperitoneal cisplatin improves treatment outcome in ovarian cancer mouse models. J. Control. Release,, 2015, 220(Pt A), 358-367.
[http://dx.doi.org/10.1016/j.jconrel.2015.11.001] [PMID: 26548976]
[17]
Padmakumar, S.; Paul-Prasanth, B.; Pavithran, K.; Vijaykumar, D.K.; Rajanbabu, A.; Sivanarayanan, T.B.; Kadakia, E.; Amiji, M.M.; Nair, S.V.; Menon, D. Long-term drug delivery using implantable electrospun woven polymeric nanotextiles. Nanomedicine (Lond.), 2019, 15(1), 274-284.
[http://dx.doi.org/10.1016/j.nano.2018.10.002] [PMID: 30343013]
[18]
Garber, C. Guide for the Care and Use of Laboratory Animals. In Committee for the Update of the Guide for the Care and Use of Laboratory Animals, Institute for Laboratory Animal Research, Division on Earth and Life Studies, National Research Council ; 1-218.The National Academies Press: Washington D.C,, 2011, pp.
[19]
Yang, M.; Yu, T.; Wood, J.; Wang, Y.Y.; Tang, B.C.; Zeng, Q.; Simons, B.W.; Fu, J.; Chuang, C.M.; Lai, S.K.; Wu, T.C.; Hung, C.F.; Hanes, J. Intraperitoneal delivery of paclitaxel by poly(ether-anhydride) microspheres effectively suppresses tumor growth in a murine metastatic ovarian cancer model. Drug Deliv. Transl. Res., 2014, 4(2), 203-209.
[http://dx.doi.org/10.1007/s13346-013-0190-7] [PMID: 24816829]
[20]
Márquez, Y.; Franco, L.; Turon, P.; Martínez, J.C.; Puiggalí, J. Study of Non-isothermal crystallization of polydioxanone and analysis of morphological changes occurring during heating and cooling processes. Polymers (Basel), 2016, 8(10), 1-18.
[http://dx.doi.org/10.3390/polym8100351] [PMID: 30974626]
[21]
Van der Speeten, K.; Stuart, O.A.; Sugarbaker, P.H. Using pharmacologic data to plan clinical treatments for patients with peritoneal surface malignancy. Curr. Drug Discov. Technol., 2009, 6(1), 72-81.
[http://dx.doi.org/10.2174/157016309787581084] [PMID: 19275544]
[22]
Huang, X.; Brazel, C.S. On the importance and mechanisms of burst release in matrix-controlled drug delivery systems. J. Control. Release, 2001, 73(2-3), 121-136.
[http://dx.doi.org/10.1016/S0168-3659(01)00248-6] [PMID: 11516493]
[23]
Kopcinovic, L.M.; Culej, J. Pleural, peritoneal and pericardial effusions - a biochemical approach. Biochem. Med. (Zagreb), 2014, 24(1), 123-137.
[http://dx.doi.org/10.11613/BM.2014.014] [PMID: 24627721]
[24]
Kelton, J.G.; Ulan, R.; Stiller, C.; Holmes, E. Comparison of chemical composition of peritoneal fluid and serum: A method for monitoring dialysis patients and a tool for assessing binding to serum proteins. In vivo. Ann. Intern. Med., 1978, 89(1), 67-70.
[http://dx.doi.org/10.7326/0003-4819-89-1-67] [PMID: 666190]
[25]
Prevorsek, D.C. Recent Advances in Polymer Chemical Physics; In Contributions of the Russian Academy of Sciences, CRC Press, 1998, p. 386.
[26]
Kipps, E.; Tan, D.S.P.; Kaye, S.B. Meeting the challenge of ascites in ovarian cancer: New avenues for therapy and research. Nat. Rev. Cancer, 2013, 13(4), 273-282.
[http://dx.doi.org/10.1038/nrc3432] [PMID: 23426401]
[27]
Https://Www.Mlo-Online.Com/Pleural-Peritoneal-FluidsMedicalLaboratory Observer (MLO). Pleural and Peritoneal Fluids - MLO.. 2016.
[28]
Noh, S-M. Measurement of peritoneal fluid pH in patients with non-serosal invasive gastric cancer. Yonsei Med. J., 2003, 44(1), 45-48.
[http://dx.doi.org/10.3349/ymj.2003.44.1.45] [PMID: 12619174]
[29]
Steele, T.W.; Huang, C.L.; Kumar, S.; Iskandar, A.; Baoxin, A.; Yin, F.; Boey, C.; Loo, J.S.; Venkatraman, S.S. Tuning drug release in polyester thin films: Terminal end-groups determine specific rates of additive-free controlled drug release. NPG Asia Mater., 2013, 9.
[http://dx.doi.org/10.1038/am.2013.9]
[30]
Zilberman, M. Dexamethasone loaded bioresorbable films used in medical support devices: Structure, degradation, crystallinity and drug release. Acta Biomater., 2005, 1(6), 615-624.
[http://dx.doi.org/10.1016/j.actbio.2005.06.007] [PMID: 16701842]
[31]
Chen, V.J.; Ma, P.X. The effect of surface area on the degradation rate of nano-fibrous poly(L-lactic acid) foams. Biomaterials, 2006, 27(20), 3708-3715.
[http://dx.doi.org/10.1016/j.biomaterials.2006.02.020] [PMID: 16519935]
[32]
Sabino, M.A.; González, S.; Márquez, L.; Feijoo, J.L. Study of the hydrolytic degradation of polydioxanone PPDX. Polym. Degrad. Stabil., 2000, 69(2), 209-216.
[http://dx.doi.org/10.1016/S0141-3910(00)00062-8]
[33]
Vasile, C. Micro and nano technologies. Polymeric Nanomaterials in Nanotherapeutics; Elsevier, 2018, p. 558.
[34]
Jacquet, P.; Sugarbaker, P.P.H. Peritoneal-Plasma Barrier. Peritoneal Carcinomatosis: Principles of ManagementCancer Treatment and ResearchSpringer: Boston, MA, 1996, p. 82.
[35]
Lengyel, E. Ovarian cancer development and metastasis. Am. J. Pathol., 2010, 177(3), 1053-1064.
[http://dx.doi.org/10.2353/ajpath.2010.100105] [PMID: 20651229]
[36]
Dedrick, R.L.; Flessner, M.F. Pharmacokinetic problems in peritoneal drug administration: Tissue penetration and surface exposure. J. Natl. Cancer Inst., 1997, 89(7), 480-487.
[http://dx.doi.org/10.1093/jnci/89.7.480] [PMID: 9086004]
[37]
Innocenti, F.; Danesi, R.; Di Paolo, A.; Agen, C.; Nardini, D.; Bocci, G.; Del Tacca, M. Plasma and tissue disposition of paclitaxel (taxol) after intraperitoneal administration in mice. Drug Metab. Dispos., 1995, 23(7), 713-717.
[PMID: 7587959]
[38]
Vassileva, V.; Allen, C.J.; Piquette-Miller, M. Effects of sustained and intermittent paclitaxel therapy on tumor repopulation in ovarian cancer. Mol. Cancer Ther., 2008, 7(3), 630-637.
[http://dx.doi.org/10.1158/1535-7163.MCT-07-2117] [PMID: 18347149]
[39]
Davis, A.J.; Tannock, J.F. Repopulation of tumour cells between cycles of chemotherapy: A neglected factor. Lancet Oncol., 2000, 1(2), 86-93.
[http://dx.doi.org/10.1016/S1470-2045(00)00019-X] [PMID: 11905673]

Rights & Permissions Print Cite
Article Metrics
35
3
1
1
© 2024 Bentham Science Publishers | Privacy Policy