Login Register Cart 0
Generic placeholder image

Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1573-4064
ISSN (Online): 1875-6638

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

Synthesis, Characterization, and Investigation of Doxorubicin Drug Release Properties of Poly(acrylamide-co-acrylic Acid/Maleic Acid)-Hydroxyapatite Composite Hydrogel

Author(s): Birnur Akkaya* and Recep Akkaya

Volume 20, Issue 5, 2024

Published on: 24 January, 2024

Page: [537 - 545] Pages: 9

DOI: 10.2174/0115734064268726231203164405

Price: $65

conference banner
Abstract

Background: Hydroxyapatite and its derivatives have been used for a lot of applications. One of them is drug release studies. Due to its low adhesion strength and lack of the strength and durability required for load-carrying applications, there is a need to improve the properties of hydroxyapatite. For this aim, the most important factors are increasing pH sensitivity and preventing coagulation. Mixing it with multifunctional polymers is the best solution.

Objectives: The main objectives are: 1- preparing poly(acrylamide-co-acrylic acid/maleic acid)- hydroxyapatite (PAm-co-PAA/PMA–HApt), 2- assessment of (PAm-co-PAA/PMA–HApt) and dox-loaded poly(acrylamide-co-acrylic acid/maleic acid) (Dox-(PAm-co-PAA/PMA–HApt)) composite hydrogels, and 3- elucidating the difference in behavior of drug release studies between hydroxyapatite (HApt) and poly(acrylamide-co-acrylic acid/maleic acid) composite hydrogels.

Methods: A composite of PAm-co-PAA/PMA–HApt was prepared by direct polymerization of acrylamide-co-acrylic acid/maleic acid in a suspension of HApt. The drug loading and release features of PAm-co-PAA/PMA–HApt and HApt were then investigated for doxorubicin (dox) release. Using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and thermogravimetric analysis (TG/DTA), this unique composite hydrogel has been physicochemically investigated. Also, a colorimetric assay was used to assess the in vitro biocompatible support and anticancer activity of HApt and the newly developed composite hydrogel XTT (2,3-Bis-(2-Methoxy-4-Nitro-5-Sulfophenyl)-2H-Tetrazolium-5-Carboxanilide) assay.

Results: According to the results of drug release studies of this new material, it is pH sensitive, and PAm-co-PAA/PMA–HApt demonstrated a faster release than HApt at 37°C in the acidic solution of pH 4.5 than in the neutral solution of pH 7.4. The XTT assay outcomes also demonstrated the biocompatibility of PAm-co-PAA/PMA–HApt and HApt and the cytotoxic effect of dox-loaded PAm-co-PAA/PMA–HApt.

Conclusion: It should be inferred that the drug release profile was improved at pH 4.5 by the newly produced pH-sensitive composite hydrogel.

« Previous Next »
Graphical Abstract

[1]
Rodrigo-Navarro, A.; Sankaran, S.; Dalby, M.J.; del Campo, A.; Salmeron-Sanchez, M. Engineered living biomaterials. Nat. Rev. Mater., 2021, 6(12), 1175-1190.
[http://dx.doi.org/10.1038/s41578-021-00350-8]
[2]
Abere, D.V.; Ojo, S.A.; Oyatogun, G.M.; Paredes-Epinosa, M.B.; Niluxsshun, M.C.D.; Hakami, A. Mechanical and morphological characterization of nano-hydroxyapatite (nHA) for bone regeneration: A mini review. Adv. Biomed. Eng., 2022, 4, 100056.
[3]
Sohn, H.S.; Oh, J.K. Review of bone graft and bone substitutes with an emphasis on fracture surgeries. Biomater. Res., 2019, 23(1), 9.
[http://dx.doi.org/10.1186/s40824-019-0157-y] [PMID: 30915231]
[4]
Fiume, E.; Magnaterra, G.; Rahdar, A.; Verné, E.; Baino, F. Hydroxyapatite for biomedical applications: A short overview. Ceramics, 2021, 4(4), 542-563.
[http://dx.doi.org/10.3390/ceramics4040039]
[5]
Li, D.; Huang, X.; Wu, Y.; Li, J.; Cheng, W.; He, J.; Tian, H.; Huang, Y. Preparation of pH-responsive mesoporous hydroxyapatite nanoparticles for intracellular controlled release of an anticancer drug. Biomater. Sci., 2016, 4(2), 272-280.
[http://dx.doi.org/10.1039/C5BM00228A] [PMID: 26484364]
[6]
Akkaya, B. Separation of lysozyme with magnetically stabilized spherical hydroxyapatite microcomposites in a continuous flow system. J. Appl. Polym. Sci., 2013, 130(3), 1602-1610.
[http://dx.doi.org/10.1002/app.39289]
[7]
Huang, H.; Du, M.; Chen, J.; Zhong, S.; Wang, J. Preparation and characterization of abalone shells derived biological mesoporous hydroxyapatite microspheres for drug delivery. Mater. Sci. Eng. C, 2020, 113, 110969.
[http://dx.doi.org/10.1016/j.msec.2020.110969] [PMID: 32487387]
[8]
Yan-Hua, W.; Hang, H.; Jian-Xiong, W.; Yuan, Y.; Na, Q.; Wen-Cong, H. Enhanced antitumor effect and drug delivery from se doped hydroxyapatite microspheres. Wuji Huaxue Xuebao, 2018, 34(8), 1517-1530.
[9]
Wang, Y.; He, W.; Hao, H.; Wu, J.; Qin, N. Eggshell derived Se-doped HA nanorods for enhanced antitumor effect and curcumin delivery. J. Sol-Gel Sci. Technol., 2018, 87(3), 600-607.
[http://dx.doi.org/10.1007/s10971-018-4765-0]
[10]
Oledzka, E.; Sobczak, M.; Kolmas, J.; Nalecz-Jawecki, G. Selenium-substituted hydroxyapatite/biodegradable polymer/pamidronate combined scaffold for the therapy of bone tumour. Int. J. Mol. Sci., 2015, 16(9), 22205-22222.
[http://dx.doi.org/10.3390/ijms160922205] [PMID: 26389884]
[11]
Gao, J.; Huang, J.; Shi, R.; Wei, J.; Lei, X.; Dou, Y.; Li, Y.; Zuo, Y.; Li, J. Loading and releasing behavior of selenium and doxorubicin hydrochloride in hydroxyapatite with different morphologies. ACS Omega, 2021, 6(12), 8365-8375.
[http://dx.doi.org/10.1021/acsomega.1c00092] [PMID: 33817497]
[12]
El Sayed, M.M. Production of polymer hydrogel composites and their applications. J. Polym. Environ., 2023, 31(7), 2855-2879.
[http://dx.doi.org/10.1007/s10924-023-02796-z]
[13]
Li, Z.; Mi, W.; Wang, H.; Su, Y.; He, C. Nano-hydroxyapatite/polyacrylamide composite hydrogels with high mechanical strengths and cell adhesion properties. Colloids Surf. B Biointerfaces, 2014, 123, 959-964.
[http://dx.doi.org/10.1016/j.colsurfb.2014.10.050] [PMID: 25465752]
[14]
Amjad, Z. Effect of thermal treatment on the performance of polymers as calcium hydroxyapatite dispersants. Phosphorus Res. Bull., 2006, 20, 155-158.
[http://dx.doi.org/10.3363/prb.20.155]
[15]
Diken, M.E.; Doğan, S.; Doğan, M.; Turhan, Y. Synthesis and characterization of poly(acrylic acid)/nanohydroxyapatite nanocomposite hydrogels and evaluation of its antibacterial, bio- and hemo-compatibility characteristics. Int. J. Polym. Mater., 2022, 71(18), 1425-1436.
[http://dx.doi.org/10.1080/00914037.2021.1981320]
[16]
Sözügeçer, S.; Bayramgil, N.P. Preparation and characterization of polyacrylic acid-hydroxyapatite nanocomposite by microwave-assisted synthesis method. Heliyon, 2021, 7(6), e07226.
[http://dx.doi.org/10.1016/j.heliyon.2021.e07226] [PMID: 34195399]
[17]
Akkaya, R.; Akkaya, B.; Çakıcı, G.T. Chitosan–poly (Acrylamide-Co-Maleic Acid) composite synthesis, characterization, and i̇nvestigation of protein adsorption behavior. Polym. Bull., 2022, 1-16.
[18]
Kim, H.; Mondal, S.; Bharathiraja, S.; Manivasagan, P.; Moorthy, M.S.; Oh, J. Optimized Zn-doped hydroxyapatite/doxorubicin bioceramics system for efficient drug delivery and tissue engineering application. Ceram. Int., 2018, 44(6), 6062-6071.
[http://dx.doi.org/10.1016/j.ceramint.2017.12.235]
[19]
Zıad, J.O.H.A.; Yulak, F.; Öztürk, A.; Şahin, B.; Yıldırım, Ş. The anticancer effect of cannabinoid 2 agonist L-759,633 On C6 And Sh-Sy5y cell lines. Turk. J. Sci. Health, 2021, 2(3), 6-13.
[20]
Flores, V.J.D.; Sáenz, G.A.; López, B.C.M.; Castañeda, F.A.O.; Acuña, V.P. Hydroxyapatite and biopolymer composites with promising biomedical applications. Rev. Mex. Ing. Biomed., 2022, 43(2)
[21]
Hassan, H.S.; El-Kamash, A.M.; Ibrahim, H.A.S. Evaluation of hydroxyapatite/poly(acrylamide-acrylic acid) for sorptive removal of strontium ions from aqueous solution. Environ. Sci. Pollut. Res. Int., 2019, 26(25), 25641-25655.
[http://dx.doi.org/10.1007/s11356-019-05755-1] [PMID: 31267395]
[22]
Jiménez-Reyes, M.; Almazán-Sánchez, P.T.; Jiménez-Becerril, J.; Solache-Ríos, M. Adsorption of 177Lu from water by using synthetic hydroxyapatite. Water Air Soil Pollut., 2021, 232(10), 394.
[http://dx.doi.org/10.1007/s11270-021-05339-1]
[23]
Cao, T.; Tang, W.; Zhao, J.; Qin, L.; Lan, C. A novel drug delivery carrier based on α-eleostearic acid grafted hydroxyapatite composite. J. Bionics Eng., 2014, 11(1), 125-133.
[http://dx.doi.org/10.1016/S1672-6529(14)60027-5]
[24]
Bajpai, A.K.; Singh, R. Preparation and characterization of hydroxyapatite impregnated semi‐interpenetrating polymer networks (IPNs) of polyvinyl alcohol and poly(Acrylamide‐ co ‐acrylic Acid). J. Macromol. Sci. Part A Pure Appl. Chem., 2004, 41(10), 1135-1159.
[http://dx.doi.org/10.1081/MA-200026560]
[25]
Moharram, M.A.; Allam, M.A. Study of the interaction of poly(acrylic acid) and poly(acrylic acid‐poly acrylamide) complex with bone powders and hydroxyapatite by using TGA and DSC. J. Appl. Polym. Sci., 2007, 105(6), 3220-3227.
[http://dx.doi.org/10.1002/app.26267]
[26]
Chutong, S.C.S.; Li Zhang, L.Z.; Honglei, Y.H.G.H.Y.H.G.; Gu, H.B. DOX-Loaded gelatin composite hydrogels with oxidation-triggered drug release property. J. Chem. Soc. Pak., 2021, 43(2), 180.
[http://dx.doi.org/10.52568/000569]
[27]
Lu, Y.; Wan, Y.; Gan, D.; Zhang, Q.; Luo, H.; Deng, X.; Li, Z.; Yang, Z. Enwrapping polydopamine on doxorubicin-loaded lamellar hydroxyapatite/poly(lactic-co-glycolic acid) composite fibers for inhibiting bone tumor recurrence and enhancing bone regeneration. ACS Appl. Bio Mater., 2021, 4(8), 6036-6045.
[http://dx.doi.org/10.1021/acsabm.1c00297] [PMID: 35006872]
[28]
Munir, M.U.; Salman, S.; Javed, I.; Bukhari, S.N.A.; Ahmad, N.; Shad, N.A.; Aziz, F. Nano-hydroxyapatite as a delivery system: Overview and advancements. Artif. Cells Nanomed. Biotechnol., 2021, 49(1), 717-727.
[http://dx.doi.org/10.1080/21691401.2021.2016785] [PMID: 34907839]
[29]
Wang, H.; He, L.; Zhang, P.; Zhang, J.; Chen, Z.; Ren, X.; Mei, X. Folate-modified hydroxyapatite nanorods induce apoptosis in MCF-7 cells through a mitochondrial-dependent pathway. New J. Chem., 2019, 43(37), 14728-14738.
[http://dx.doi.org/10.1039/C9NJ03653A]
[30]
Aval, N.; Islamian, J.; Hatamian, M.; Arabfirouzjaei, M.; Javadpour, J.; Rashidi, M.R. Doxorubicin loaded large-pore mesoporous hydroxyapatite coated superparamagnetic Fe 3 O 4 nanoparticles for cancer treatment. Int. J. Pharm., 2016, 509(1-2), 159-167.
[http://dx.doi.org/10.1016/j.ijpharm.2016.05.046] [PMID: 27234695]
[31]
Ghosh, S.; Ghosh, S.; Pramanik, N. Bio-evaluation of doxorubicin (DOX)-incorporated hydroxyapatite (HAp)-chitosan (CS) nanocomposite triggered on osteosarcoma cells. Adv. Compos. Hybrid Mater., 2020, 3(3), 303-314.
[http://dx.doi.org/10.1007/s42114-020-00154-4]
[32]
Fadli, A.; Yenti, S.R.; Irianty, R.S.; Marbun, U.N. Effect of ph value and doxorubicin/hydroxyapatite ratio on the release of doxorubicin from hydroxyapatite surface in phosphate buffered saline (Pbs). International Conference Of Celscitech 2019-Science And Technology Track (Iccelst-St 2019), 2019, pp. 34-37.
[http://dx.doi.org/10.2991/iccelst-st-19.2019.7]
[33]
Rong, Z.J.; Yang, L.J.; Cai, B.T.; Zhu, L.X.; Cao, Y.L.; Wu, G.F.; Zhang, Z.J. Porous nano-hydroxyapatite/collagen scaffold containing drug-loaded ADM–PLGA microspheres for bone cancer treatment. J. Mater. Sci. Mater. Med., 2016, 27(5), 89.
[http://dx.doi.org/10.1007/s10856-016-5699-0] [PMID: 26975746]
[34]
Luo, H.; Zhang, Y.; Yang, Z.; Zuo, G.; Zhang, Q.; Yao, F.; Wan, Y. Encapsulating doxorubicin-intercalated lamellar nanohydroxyapatite into PLGA nanofibers for sustained drug release. Curr. Appl. Phys., 2019, 19(11), 1204-1210.
[http://dx.doi.org/10.1016/j.cap.2019.08.003]
[35]
Wu, M.Y.; Liang, Y.H.; Yen, S.K. Effects of chitosan on loading and releasing for doxorubicin loaded porous hydroxyapatite–gelatin composite microspheres. Polymers, 2022, 14(20), 4276.
[http://dx.doi.org/10.3390/polym14204276] [PMID: 36297854]
[36]
Taleb, M.F.; Alkahtani, A.; Mohamed, S.K. Radiation synthesis and characterization of sodium alginate/chitosan/hydroxy-apatite nanocomposite hydrogels: A drug delivery system for liver cancer. Polym. Bull., 2015, 72(4), 725-742.
[http://dx.doi.org/10.1007/s00289-015-1301-z]
[37]
Guo, Q.; Kong, F.; Ma, C.; Cao, H. Preparation of doxorubicin loaded poly(ethylene glycol)-Poly(ε-caprolactone)-hydroxyapatite fibres as drug delivery systems. Mater. Technol., 2020, 35(4), 203-211.
[http://dx.doi.org/10.1080/10667857.2019.1674477]
[38]
Kong, L.; Mu, Z.; Yu, Y.; Zhang, L.; Hu, J. Polyethyleneimine-stabilized hydroxyapatite nanoparticles modified with hyaluronic acid for targeted drug delivery. RSC Advan., 2016, 6(104), 101790-101799.
[http://dx.doi.org/10.1039/C6RA19351J]
[39]
Zhou, L.; Zhang, Y.; Zeng, D.; Shu, T.; Wang, S. Dual-responsive mesoporous poly-N-isopropylacrylamide-hydroxyapatite composite microspheres for controlled anticancer drug delivery. J. Sol-Gel Sci. Technol., 2021, 97(3), 600-609.
[http://dx.doi.org/10.1007/s10971-020-05460-3]
[40]
Sumathra, M.; Rajan, M.; Amarnath, P.R.; Marraiki, N.; Elgorban, A.M. In vivo assessment of a hydroxyapatite/κ-carrageenan–maleic anhydride–casein/doxorubicin composite-coated titanium bone implant. ACS Biomater. Sci. Eng., 2020, 6(3), 1650-1662.
[http://dx.doi.org/10.1021/acsbiomaterials.9b01750] [PMID: 33455363]
[41]
Zhao, D.; Zhu, T.T.; Li, J.; Cui, L.G.; Zhang, Z.Y.; Zhuang, X.L.; Ding, J.X. Poly(lactic-co-glycolic acid)-based composite bone-substitute materials. Bioact. Mater., 2021, 6, 346-360.
[42]
Deng, T.; Luo, D.; Zhang, R.; Zhao, R.; Hu, Y.; Zhao, Q.; Wang, S.; Iqbal, M.Z.; Kong, X. DOX-loaded hydroxyapatite nanoclusters for colorectal cancer (CRC) chemotherapy: Evaluation based on the cancer cells and organoids. SLAS Technol., 2023, 28(1), 22-31.
[http://dx.doi.org/10.1016/j.slast.2022.10.002] [PMID: 36328181]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy