Hostname: page-component-586b7cd67f-2brh9 Total loading time: 0 Render date: 2024-11-24T02:50:15.976Z Has data issue: false hasContentIssue false

Effects of polymer chemistry, concentration, and pH on doxorubicin release kinetics from hydroxyapatite-PCL-PLGA composite

Published online by Cambridge University Press:  20 May 2019

Dishary Banerjee
Affiliation:
W. M. Keck Biomedical Materials Research Laboratory, School of Mechanical and Materials Engineering, Washington State University, Pullman, Washington 99164-2920, USA
Susmita Bose*
Affiliation:
W. M. Keck Biomedical Materials Research Laboratory, School of Mechanical and Materials Engineering, Washington State University, Pullman, Washington 99164-2920, USA
*
a)Address all correspondence to this author. e-mail: [email protected]
Get access

Abstract

The objective of this study was to understand the effects of ceramic polymer composite and pH of the surrounding vicinity on the release kinetics of doxorubicin. Different concentrations of polymers with polycaprolactone (PCL), poly glycolic lactic acid (PLGA), and a blend of PCL–PLGA with hydroxyapatite (HA) were investigated for doxorubicin release at physiological pH of 7.4 and an acidic pH of 5.0 caused by immediate surgery. Burst release of 20% was observed from bare HA at pH 7.4 over a week, whereas all the polymer incorporated discs showed sustained release. The hydrophilic–hydrophobic and hydrophobic–hydrophobic interactions between the polymer and the drug altered by the surrounding pHs were found to be pivotal in controlling the release kinetics of drug. No cytotoxicity of the drug at a concentration of 50 μg per disc was observed at early time points when cultured with osteoblast cells; however, the same drug dosage inhibited osteosarcoma cell viability. This study mainly bases on the comprehension of the effects of chemistry, environment, and polymer–drug interactions, leading to a beneficial understanding towards the design of drug delivery devices.

Type
Article
Copyright
Copyright © Materials Research Society 2019 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

b)

This author was an editor of this journal during the review and decision stage. For the JMR policy on review and publication of manuscripts authored by editors, please refer to http://www.mrs.org/editor-manuscripts/.

References

Alkhraisat, M.H., Rueda, C., Cabrejos-Azama, J., Lucas-Aparicio, J., Mariño, F.T., Garcia-Denche, J.T., Blanco Jerez, L., Gbureck, U., and Cabarcos, E.L.: Loading and release of doxycycline hyclate from strontium-substituted calcium phosphate cement. Acta Biomater. 6, 15221528 (2010).CrossRefGoogle ScholarPubMed
Otto, D.P., de Villiers, M.M., de Villiers, M.M., Aramwit, P., and Kwon, G.S.: Nanotechnology in Drug Delivery (American Association of Pharmaceutical Science (AAPS) Press, Springer-Verlag, New York, 2009).Google Scholar
Bandyopadhyay, A., Bernard, S., Xue, W., and Bose, S.: Calcium phosphate-based resorbable ceramics: Influence of MgO, ZnO, and SiO2 dopants. J. Am. Ceram. Soc. 89, 26752688 (2006).CrossRefGoogle Scholar
Rey, C.: Calcium phosphate biomaterials and bone mineral. Differences in composition, structures and properties. Biomaterials 11, 1315 (1990).Google ScholarPubMed
Dasgupta, S., Banerjee, S.S., Bandyopadhyay, A., and Bose, S.: Zn-and Mg-doped hydroxyapatite nanoparticles for controlled release of protein. Langmuir 26, 49584964 (2010).CrossRefGoogle ScholarPubMed
Nandi, S.K., Fielding, G., Banerjee, D., Bandyopadhyay, A., and Bose, S.: 3D-printed β-TCP bone tissue engineering scaffolds: Effects of chemistry on in vivo biological properties in a rabbit tibia model. J. Mater. Res. 33, 19391947 (2018).CrossRefGoogle Scholar
Vallet-Regí, M., Balas, F., and Arcos, D.: Mesoporous materials for drug delivery. Angew. Chem., Int. Ed. 46, 75487558 (2007).CrossRefGoogle ScholarPubMed
Bose, S. and Tarafder, S.: Calcium phosphate ceramic systems in growth factor and drug delivery for bone tissue engineering: A review. Acta Biomater. 8, 14011421 (2012).CrossRefGoogle ScholarPubMed
Reginster, J.Y. and Burlet, N.: Osteoporosis: A still increasing prevalence. Bone 38, S4S9 (2006).CrossRefGoogle ScholarPubMed
Pastorino, D., Canal, C., and Ginebra, M.P.: Drug delivery from injectable calcium phosphate foams by tailoring the macroporosity–drug interaction. Acta Biomater. 12, 250259 (2015).CrossRefGoogle ScholarPubMed
Kantoff, P.W., Higano, C.S., Shore, N.D., Roy Berger, E., Small, E.J., Penson, D.F., Redfern, C.H., Ferrari, A.C., Dreicer, R., Sims, R.B., Xu, Y., Frohlich, M.W., and Schellhammer, P.F.: Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N. Engl. J. Med. 363, 411422 (2010).CrossRefGoogle ScholarPubMed
Lee, D.W., Barrett, D.M., Mackall, C., Orentas, R., and Grupp, S.A.: The future is now: Chimeric antigen receptors as new targeted therapies for childhood cancer 18, 27802790 (2012).Google Scholar
Vasir, J.K. and Labhasetwar, V.: Targeted drug delivery in cancer therapy. Technol. Cancer Res. Treat. 4, 363374 (2005).CrossRefGoogle ScholarPubMed
Banerjee, D. and Bose, S.: Comparative effects of controlled release of sodium bicarbonate and doxorubicin on osteoblast and osteosarcoma cell viability. Mater. Today Chem. 12, 200208 (2019).CrossRefGoogle Scholar
Kang, Y., Siegel, P.M., Shu, W., Drobnjak, M., Kakonen, S.M., Cordón-Cardo, C., Guise, T.A., and Massagué, J.: A multigenic program mediating breast cancer metastasis to bone. Cancer Cell 3, 537549 (2003).CrossRefGoogle ScholarPubMed
Capranico, G., Tinelli, S., Zunino, F., Kohn, K.W., and Pommier, Y.: Effects of base mutations on topoisomerase II DNA cleavage stimulated by mAMSA in short DNA oligomers. Biochemistry 32, 145152 (1993).CrossRefGoogle ScholarPubMed
Pigram, W.J., Fuller, W., and Hamilton, L.D.: Stereochemistry of intercalation: Interaction of daunomycin with DNA. Nat. New Biol. 235, 17 (1972).CrossRefGoogle ScholarPubMed
Xue, W., Bandyopadhyay, A., and Bose, S.: Polycaprolactone coated porous tricalcium phosphate scaffolds for controlled release of protein for tissue engineering. J. Biomed. Mater. Res., Part B 91, 831838 (2009).CrossRefGoogle ScholarPubMed
Takeuchi, I., Takeshita, T., Suzuki, T., and Makino, K.: Iontophoretic transdermal delivery using chitosan-coated PLGA nanoparticles for positively charged drugs. Colloids Surf., B 160, 520526 (2017).CrossRefGoogle ScholarPubMed
Coombes, A.G.A., Rizzi, S.C., Williamson, M., Barralet, J.E., Downes, S., and Wallace, W.A.: Precipitation casting of polycaprolactone for applications in tissue engineering and drug delivery. Biomaterials 25, 315325 (2004).CrossRefGoogle ScholarPubMed
Tarafder, S., Nansen, K., and Bose, S.: Lovastatin release from polycaprolactone coated β-tricalcium phosphate: Effects of pH, concentration and drug–polymer interactions. Mater. Sci. Eng., C 33, 31213128 (2013).CrossRefGoogle ScholarPubMed
Kunieda, K., Seki, T., Nakatani, S., Wakabayashi, M., Shiro, T., Inoue, K., Sougawa, M., Kimura, R., and Harada, K.: Implantation treatment method of slow release anticancer doxorubicin containing hydroxyapatite (DOX-HAP) complex. A basic study of a new treatment for hepatic cancer. Br. J. Cancer 67, 668 (1993).CrossRefGoogle ScholarPubMed
Tarafder, S., Banerjee, S., Bandyopadhyay, A., and Bose, S.: Electrically polarized biphasic calcium phosphates: Adsorption and release of bovine serum albumin. Langmuir 26, 1662516629 (2010).CrossRefGoogle ScholarPubMed
Nyan, M., Miyahara, T., Noritake, K., Hao, J., Rodriguez, R., Kuroda, S., and Kasugai, S.: Molecular and tissue responses in the healing of rat calvarial defects after local application of simvastatin combined with alpha tricalcium phosphate. J. Biomed. Mater. Res., Part B 93, 6573 (2010).Google ScholarPubMed
Radin, S., Campbell, J.T., Ducheyne, P., and Cuckler, J.M.: Calcium phosphate ceramic coatings as carriers of vancomycin. Biomaterials 18, 777782 (1997).CrossRefGoogle ScholarPubMed
Kim, H.W., Knowles, J.C., and Kim, H.E.: Hydroxyapatite/poly (ε-caprolactone) composite coatings on hydroxyapatite porous bone scaffold for drug delivery. Biomaterials 25, 12791287 (2004).CrossRefGoogle ScholarPubMed
Li, H., Hardy, R.J., and Gu, X.: Effect of drug solubility on polymer hydration and drug dissolution from polyethylene oxide (PEO) matrix tablets. AAPS PharmSciTech 9, 437443 (2008).CrossRefGoogle ScholarPubMed
Tarafder, S. and Bose, S.: Polycaprolactone-coated 3D printed tricalcium phosphate scaffolds for bone tissue engineering: In vitro alendronate release behavior and local delivery effect on in vivo osteogenesis. ACS Appl. Mater. Interfaces 6, 99559965 (2014).CrossRefGoogle ScholarPubMed
Saylor, D.M., Kim, C.S., Patwardhan, D.V., and Warren, J.A.: Modeling microstructure development and release kinetics in controlled drug release coatings. J. Pharm. Sci. 98, 169186 (2009).CrossRefGoogle ScholarPubMed
Siepmann, J., Lecomte, F., and Bodmeier, R.: Diffusion-controlled drug delivery systems: Calculation of the required composition to achieve desired release profiles. J. Controlled Release 60, 379389 (1999).CrossRefGoogle ScholarPubMed
Hongquan, Z., Yuhua, Y., Youfa, W., and Shipu, L.: Morphology and formation mechanism of hydroxyapatite whiskers from moderately acid solution. Mater. Res. 6, 111115 (2003).CrossRefGoogle Scholar
Xiong, H., Du, S., Ni, J., Zhou, J., and Yao, J.: Mitochondria and nuclei dual-targeted heterogeneous hydroxyapatite nanoparticles for enhancing therapeutic efficacy of doxorubicin. Biomaterials 94, 7083 (2016).CrossRefGoogle ScholarPubMed
Zheng, F., Wang, S., Shen, M., Zhu, M., and Shi, X.: Antitumor efficacy of doxorubicin-loaded electrospun nano-hydroxyapatite–poly(lactic-co-glycolic acid) composite nanofibers. Polym. Chem. 4, 933941 (2013).CrossRefGoogle Scholar