Skip to main content

Advertisement

SpringerLink
Log in

Old drug, new tricks: polymer-based nanoscale systems for effective cytarabine delivery

  • Review
  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Abstract

Cytarabine, an antimetabolite antineoplastic agent, has been utilized to treat various cancers. However, because of its short half-life, low stability, and limited bioavailability, achieving an optimal plasma concentration requires continuous intravenous administration, which can lead to toxicity in normal cells and tissues. Addressing these limitations is crucial to optimize the therapeutic efficacy of cytarabine while minimizing its adverse effects. The use of novel drug delivery systems, such as polymer-based nanocarriers have emerged as promising vehicles for targeted drug delivery due to their unique properties, including high stability, biocompatibility, and tunable release kinetics. In this review, we examine the application of various polymer-based nanocarriers, including polymeric nanoparticles, polymeric micelles, dendrimers, polymer-drug conjugates, and nano-hydrogels, for the delivery of cytarabine. The article highlights the limitations of conventional cytarabine administration which often lead to suboptimal therapeutic outcomes and systemic toxicity. The rationale for using polymer-based nanocarriers is discussed, highlighting their ability to overcome challenges by providing controlled drug release, improved stability, and enhanced targeting capabilities. In summary, this review offers a valuable resource for drug delivery scientists by providing insights into the design principles, formulation strategies, and potential applications of polymer-based nanocarriers that can enhance the therapeutic efficacy of cytarabine.

Graphical Abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Copyright 2018, Elsevier

Fig. 5

Copyright 2021, Royal Society of Chemistry

Fig. 6

Copyright 2014, Elsevier

Similar content being viewed by others

Data Availability

Data related to this study are available within the manuscript.

References

  • Abalı, H, Ürün, Y, Öksüzoğlu, B, Budakoğlu, B, Yıldırım, N, Güler, T, . . . Zengin, N (2008) Comparison of ICE (ifosfamide-carboplatin-etoposide) versus DHAP (cytosine arabinoside-cisplatin-dexamethasone) as salvage chemotherapy in patients with relapsed or refractory lymphoma. Cancer investigation, 26(4), 401–406

  • Abbasi R, Shineh G, Mobaraki M, Doughty S, Tayebi L (2023) Structural parameters of nanoparticles affecting their toxicity for biomedical applications: a review. J Nanopart Res 25(3):43

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ajnai G, Chiu A, Kan T, Cheng C-C, Tsai T-H, Chang J (2014) Trends of gold nanoparticle-based drug delivery system in cancer therapy. J Exp Clin Med 6(6):172–178

    Article  CAS  Google Scholar 

  • Akbarzadeh, A, Rezaei-Sadabady, R, Davaran, S, Joo, SW, Zarghami, N, Hanifehpour, Y, . . . Nejati-Koshki, K (2013) Liposome: classification, preparation, and applications. Nanoscale research letters, 8, 1–9

  • Allen TM, Cullis PR (2013) Liposomal drug delivery systems: from concept to clinical applications. Adv Drug Deliv Rev 65(1):36–48

    Article  CAS  PubMed  Google Scholar 

  • Babar Q, Saeed A, Tabish TA, Sarwar M, Thorat ND (2023) Targeting the tumor microenvironment: potential strategy for cancer therapeutics. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease 166746(6):166746. https://doi.org/10.1016/j.bbadis.2023.166746

    Article  CAS  Google Scholar 

  • Badshah SF, Akhtar N, Minhas MU, Khan KU, Khan S, Abdullah O, Naeem A (2021) Porous and highly responsive cross-linked β-cyclodextrin based nanomatrices for improvement in drug dissolution and absorption. Life Sci 267:118931

    Article  CAS  PubMed  Google Scholar 

  • Batool, N, Sarfraz, RM, Mahmood, A, Rehman, U, Zaman, M, Akbar, S, . . . Gad, HA (2023) Development and evaluation of cellulose derivative and pectin based swellable pH responsive hydrogel network for controlled delivery of cytarabine. Gels, 9(1), 60

  • Baumann, S, Huseynov, A, Goranova, D, Faust, M, Behnes, M, Nolte, F, . . . Akin, I (2014) Takotsubo cardiomyopathy after systemic consolidation therapy with high-dose intravenous cytarabine in a patient with acute myeloid leukemia. Oncol Res Treat, 37(9), 487–490

  • Baumhäkel, M, Kasel, D, Rao-Schymanski, R, Böcker, R, Beckurts, K, Zaigler, M, . . . Fuhr, U (2001) Screening for inhibitory effects of antineoplastic agents on CYP3A4 in human liver microsomes. Int J Clin Pharmacol Ther, 39(12), 517–528

  • Biswas S, Kumari P, Lakhani PM, Ghosh B (2016) Recent advances in polymeric micelles for anti-cancer drug delivery. Eur J Pharm Sci 83:184–202

    Article  CAS  PubMed  Google Scholar 

  • Bokstein F, Goor O, Shihman B, Rochkind S, Even-Sapir E, Metser U, Neufeld M (2005) Assessment of neurolymphomatosis by brachial plexus biopsy and PET/CT. Report of a case. J Neuro-Oncol 72(2):163–167

    Article  Google Scholar 

  • Bose RJ, Ravikumar R, Karuppagounder V, Bennet D, Rangasamy S, Thandavarayan RA (2017) Lipid–polymer hybrid nanoparticle-mediated therapeutics delivery: advances and challenges. Drug Discovery Today 22(8):1258–1265

    Article  CAS  PubMed  Google Scholar 

  • Byrd, JC, Ruppert, AS, Mrózek, K, Carroll, AJ, Edwards, CG, Arthur, DC, . . . Moore, JO (2004) Repetitive cycles of high-dose cytarabine benefit patients with acute myeloid leukemia and inv (16)(p13q22) or t (16; 16)(p13; q22): results from CALGB 8461. J Clin Oncol, 22(6), 1087–1094

  • Caminade A-M, Turrin C-O (2014) Dendrimers for drug delivery. J Mater Chem B 2(26):4055–4066

    Article  CAS  PubMed  Google Scholar 

  • Chan, JM, Valencia, PM, Zhang, L, Langer, R, Farokhzad, OC (2010) Polymeric nanoparticles for drug delivery. Cancer Nanotechnol Meth Protocols, 163–175

  • Chandrakala V, Aruna V, Angajala G (2022) Review on metal nanoparticles as nanocarriers: current challenges and perspectives in drug delivery systems. Emerg Mater 5(6):1593–1615

    Article  CAS  Google Scholar 

  • Chaudhuri, A, Kumar, DN, Shaik, RA, Eid, BG, Abdel-Naim, A B, Md, S, . . . Agrawal, AK (2022) Lipid-based nanoparticles as a pivotal delivery approach in triple negative breast cancer (TNBC) therapy. Int J Mol Sci, 23(17), 10068

  • Chauhan I, Yasir M, Verma M, Singh AP (2020) Nanostructured lipid carriers: a groundbreaking approach for transdermal drug delivery. Adv Pharmaceut Bull 10(2):150

    Article  CAS  Google Scholar 

  • Chhikara BS, Parang K (2010) Development of cytarabine prodrugs and delivery systems for leukemia treatment. Expert Opin Drug Deliv 7(12):1399–1414. https://doi.org/10.1517/17425247.2010.527330

    Article  CAS  PubMed  Google Scholar 

  • Cole N, Gibson B (1997) High-dose cytosine arabinoside in the treatment of acute myeloid leukaemia. Blood Rev 11(1):39–45

    Article  CAS  PubMed  Google Scholar 

  • Couvreur, P, Stella, B, Reddy, LH, Hillaireau, H, Dubernet, C, Desmaële, D, . . . Clayette, P (2006) Squalenoyl nanomedicines as potential therapeutics. Nano Lett, 6(11), 2544–2548

  • Crain ML (2018) Daunorubicin & cytarabine liposome (vyxeos™). Oncol Times 40(10):30

    Article  Google Scholar 

  • Daniş I, Gölcü A, Durişehvar Ü (2023) Cytarabine determination from urine for toxicokinetic and excretion studies by high-performance liquid chromatography-tandem mass spectrometry. J Turk Chem Soc Sect Chem 10(2):513–520

    Article  Google Scholar 

  • de Lima PHC, Butera AP, Cabeça LF, Ribeiro-Viana RM (2021) Liposome surface modification by phospholipid chemical reactions. Chem Phys Lipid 237:105084

    Article  CAS  Google Scholar 

  • Deepa G, Sivakumar K, Sajeevan T (2018) Molecular simulation and in vitro evaluation of chitosan nanoparticles as drug delivery systems for the controlled release of anticancer drug cytarabine against solid tumours. 3 Biotech 8(12):1–11. https://doi.org/10.1007/s13205-018-1510-x

    Article  Google Scholar 

  • Di Francia, R, Crisci, S, De Monaco, A, Cafiero, C, Re, A, Iaccarino, G, . . . Micera, A (2021) Response and toxicity to cytarabine therapy in leukemia and lymphoma: from dose puzzle to pharmacogenomic biomarkers. Cancers, 13(5), 966

  • Dornbos D III, Elder JB, Otero JJ, Baiocchi RA, Slone HW, Puduvalli VK, Giglio P (2019) Spinal cord toxicity from intrathecal chemotherapy: a case with clinicopathologic correlation. World Neurosurg 128:381–384

    Article  PubMed  Google Scholar 

  • Dos Santos, CA, Seckler, MM, Ingle, AP, Gupta, I, Galdiero, S, Galdiero, M, . . . Rai, M (2014) Silver nanoparticles: therapeutical uses, toxicity, and safety issues. J Pharm Sci, 103(7), 1931–1944

  • Dristant U, Mukherjee K, Saha S, Maity D (2023) An overview of polymeric nanoparticles-based drug delivery system in cancer treatment. Technol Cancer Res Treat 22:15330338231152084

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Duan, Y, Dhar, A, Patel, C, Khimani, M, Neogi, S, Sharma, P, . . . Vekariya, RL (2020) A brief review on solid lipid nanoparticles: part and parcel of contemporary drug delivery systems. RSC Adv, 10(45), 26777–26791

  • Ekladious I, Colson YL, Grinstaff MW (2019) Polymer–drug conjugate therapeutics: advances, insights and prospects. Nat Rev Drug Discovery 18(4):273–294. https://doi.org/10.1038/s41573-018-0005-0

    Article  CAS  PubMed  Google Scholar 

  • Elsabahy M, Wooley KL (2012) Design of polymeric nanoparticles for biomedical delivery applications. Chem Soc Rev 41(7):2545–2561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • El-Subbagh HI, Al-Badr AA (2009) Cytarabine. Profiles of Drug Substances, Excipients and Related Methodology, vol. 34. Academic Press, pp. 37-113

  • Fang Z, Wang X, Sun Y, Fan R, Liu Z, Guo R, Xie D (2019) Sgc8 aptamer targeted glutathione-responsive nanoassemblies containing Ara-C prodrug for the treatment of acute lymphoblastic leukemia. Nanoscale 11(47):23000–23012

    Article  CAS  PubMed  Google Scholar 

  • Faruqi A, Tadi P (2020) Cytarabine. StatPearls Publishing, Treasure Island (FL)

  • Faruqi A, Tadi P (2022) Cytarabine. In xPharm: The Comprehensive Pharmacology Reference. Published online August, 12, 1-5

  • Feng Q, Tong R (2016) Anticancer nanoparticulate polymer-drug conjugate. Bioeng Transl Med 1(3):277–296

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Galmarini CM, Warren G, Kohli E, Zeman A, Mitin A, Vinogradov SV (2008) Polymeric nanogels containing the triphosphate form of cytotoxic nucleoside analogues show antitumor activity against breast and colorectal cancer cell lines. Mol Cancer Ther 7(10):3373–3380

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gao D, Xu H, Philbert MA, Kopelman R (2008) Bioeliminable nanohydrogels for drug delivery. Nano Lett 8(10):3320–3324

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Geethakumari D, Sathyabhama AB, Sathyan KR, Mohandas D, Somasekharan JV, Puthiyedathu ST (2022) Folate functionalized chitosan nanoparticles as targeted delivery systems for improved anticancer efficiency of cytarabine in MCF-7 human breast cancer cell lines. Int J Biol Macromol 199:150–161. https://doi.org/10.1016/j.ijbiomac.2021.12.070

    Article  CAS  PubMed  Google Scholar 

  • Ghosh B, Biswas S (2021) Polymeric micelles in cancer therapy: state of the art. J Control Release 332:127–147

    Article  CAS  PubMed  Google Scholar 

  • Gomes HI, Martins CS, Prior JA (2021) Silver nanoparticles as carriers of anticancer drugs for efficient target treatment of cancer cells. Nanomaterials 11(4):964

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guimarães D, Cavaco-Paulo A, Nogueira E (2021) Design of liposomes as drug delivery system for therapeutic applications. Int J Pharm 601:120571

    Article  PubMed  Google Scholar 

  • Hamimed S, Jabberi M, Chatti A (2022) Nanotechnology in drug and gene delivery. Naunyn Schmiedebergs Arch Pharmacol 395(7):769–787

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hussain, Z, Rahim, MA, Jan, N, Shah, H, Rawas-Qalaji, M, Khan, S, . . . Sarfraz, RM (2021) Cell membrane cloaked nanomedicines for bio-imaging and immunotherapy of cancer: improved pharmacokinetics, cell internalization and anticancer efficacy. J Control Rel

  • Jahangir MA, Taleuzzaman M, Kala C, Gilani SJ (2020) Advancements in polymer and lipid-based nanotherapeutics for cancer drug targeting. Curr Pharm Des 26(40):5119–5127

    Article  CAS  PubMed  Google Scholar 

  • Jan, N, Madni, A, Rahim, MA, Khan, NU, Jamshaid, T, Khan, A, . . . Shah, H (2021) In vitro anti-leukemic assessment and sustained release behaviour of cytarabine loaded biodegradable polymer based nanoparticles. Life Sci, 267, 118971. https://doi.org/10.1016/j.lfs.2020.118971

  • Jan, N, Madni, A, Khan, S, Shah, H, Akram, F, Khan, A, . . . Ashammakhi, N (2023) Biomimetic cell membrane‐coated poly (lactic‐co‐glycolic acid) nanoparticles for biomedical applications. Bioeng Transl Med, 8(2), e10441. https://doi.org/10.1002/btm2.10441

  • Jan, N, Madni, A, Shah, H, Khan, S, Ijaz, QA, Badshah, SF, . . . Bostanudin, MF (2023) Development and statistical optimization of polymer-based nanoparticulate delivery system for enhancing cytarabine efficacy in leukemia treatment. J Pharmaceut Innov, 1–14

  • Jin M-J, Hong J-H, Han H-K (2008) Synthesis and in-vitro evaluation of N4-amino acid derivatives of cytarabine for improving the oral delivery of cytarabine. J Pharm Investig 38(4):255–259

    Article  CAS  Google Scholar 

  • Jirasek MA, Herrington JD (2016) Cytarabine syndrome despite corticosteroid premedication in an adult undergoing induction treatment for acute myelogenous leukemia. J Oncol Pharm Pract 22(6):795–800

    Article  PubMed  Google Scholar 

  • Johnson SA (2000) Clinical pharmacokinetics of nucleoside analogues: focus on haematological malignancies. Clin Pharmacokinet 39:5–26

    Article  CAS  PubMed  Google Scholar 

  • Joseph NM, Sharma PK (2007) Cross-linked nanoparticles of cytarabine: encapsulation, storage and in-vitro release. Afr J Pharm Pharmacol 1:10–13

    Google Scholar 

  • Kahraman E, Güngör S, Özsoy Y (2017) Potential enhancement and targeting strategies of polymeric and lipid-based nanocarriers in dermal drug delivery. Ther Deliv 8(11):967–985

    Article  CAS  PubMed  Google Scholar 

  • Kamali H, Nosrati R, Malaekeh-Nikouei B (2022) Chapter 1 - nanostructures and their associated challenges for drug delivery. In: Kesharwani P, Jain NK (eds) Hybrid nanomaterials for drug delivery. Woodhead Publishing, pp 1–26

    Google Scholar 

  • Kantarjian, HM, O’Brien, S, Smith, TL, Cortes, J, Giles, FJ, Beran, M, . . . Koller, C (2000) Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia. J Clin Oncol, 18(3), 547–547

  • Kanwal U, Irfan Bukhari N, Ovais M, Abass N, Hussain K, Raza A (2018) Advances in nano-delivery systems for doxorubicin: an updated insight. J Drug Target 26(4):296–310

    Article  CAS  PubMed  Google Scholar 

  • Karakuş G, Yağlioğlu AŞ, Zengi̇n H, Karakuş N (2015) Synthesis, characterization and antiproliferative activities of novel modified poly (maleic anhydride-co-vinyl acetate)/cytosine β-darabinofuranoside hydrochloride conjugate. Marmara Pharmaceut J 19(1):73–81

    Article  Google Scholar 

  • Kong F-Y, Zhang J-W, Li R-F, Wang Z-X, Wang W-J, Wang W (2017) Unique roles of gold nanoparticles in drug delivery, targeting and imaging applications. Molecules 22(9):1445

    Article  PubMed  PubMed Central  Google Scholar 

  • Kopterides P, Lignos M, Mentzelopoulos S, Armaganidis A, Pappa V (2005) Cytarabine-induced lung injury: case report. Anticancer Drugs 16(7):743–745

    Article  CAS  PubMed  Google Scholar 

  • Krogh-Madsen M, Bender B, Jensen MK, Nielsen OJ, Friberg LE, Honoré PH (2012) Population pharmacokinetics of cytarabine, etoposide, and daunorubicin in the treatment for acute myeloid leukemia. Cancer Chemother Pharmacol 69:1155–1163

    Article  CAS  PubMed  Google Scholar 

  • Kumar A, Zhang X, Liang X-J (2013) Gold nanoparticles: emerging paradigm for targeted drug delivery system. Biotechnol Adv 31(5):593–606

    Article  CAS  PubMed  Google Scholar 

  • Kwon GS, Okano T (1996) Polymeric micelles as new drug carriers. Adv Drug Deliv Rev 21(2):107–116

    Article  CAS  Google Scholar 

  • Lancet, JE, Uy, GL, Cortes, JE, Newell, LF, Lin, TL, Ritchie, EK, . . . Solomon, SR (2018) CPX-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. J Clin Oncol, 36(26), 2684

  • Li C, Wallace S (2008) Polymer-drug conjugates: recent development in clinical oncology. Adv Drug Deliv Rev 60(8):886–898

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liao, A-M, Zhang, Y, Hou, Y, Huang, J-H, Hui, M, Lee, K-K, . . . Chun, C (2021) Preparation, characterization, and cytotoxicity evaluation of self-assembled nanoparticles of diosgenin-cytarabine conjugate. Food Chem Toxicol, 151, 112101. https://doi.org/10.1016/j.fct.2021.112101

  • Lindley C, McCune JS, Thomason TE, Lauder D, Sauls A, Adkins S, Sawyer WT (1999) Perception of chemotherapy side effects cancer versus noncancer patients. Cancer Pract 7(2):59–65

    Article  CAS  PubMed  Google Scholar 

  • Lindner, L, Ostermann, H, Hiddemann, W, Kiani, A, Würfel, M, Illmer, T, . . . Schleyer, E (2008) AraU accumulation in patients with renal insufficiency as a potential mechanism for cytarabine neurotoxicity. Int J Hematol, 88(4), 381–386

  • Liu J, Jiang Y, Cui Y, Xu C, Ji X, Luan Y (2014) Cytarabine-AOT catanionic vesicle-loaded biodegradable thermosensitive hydrogel as an efficient cytarabine delivery system. Int J Pharm 473(1–2):560–571. https://doi.org/10.1016/j.ijpharm.2014.07.032

    Article  CAS  PubMed  Google Scholar 

  • Liu J, Zhao D, Ma N, Luan Y (2016) Highly enhanced leukemia therapy and oral bioavailability from a novel amphiphilic prodrug of cytarabine. RSC Adv 6(42):35991–35999

    Article  CAS  Google Scholar 

  • Liu J, Zhao D, He W, Zhang H, Li Z, Luan Y (2017) Nanoassemblies from amphiphilic cytarabine prodrug for leukemia targeted therapy. J Colloid Interface Sci 487:239–249

    Article  CAS  PubMed  Google Scholar 

  • Liu R, Zhang J, Zhang D, Wang K, Luan Y (2018) Self-assembling nanoparticles based on cytarabine prodrug for enhanced leukemia treatment. J Mol Liq 251:178–184

    Article  CAS  Google Scholar 

  • Liu L, Xu Z, Liu Y, Yin Z-Z, Sheng Y, Ding C, Kong Y (2021) Facile synthesis of calcium carbonate/polyacrylic acid hydrogels for pH-responsive delivery of cytarabine. J Saudi Chem Soc 25(11):101344

    Article  CAS  Google Scholar 

  • Liu P, Chen G, Zhang J (2022) A review of liposomes as a drug delivery system: current status of approved products, regulatory environments, and future perspectives. Molecules 27(4):1372

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu, Q, Wang, H, Li, G, Liu, M, Ding, J, Huang, X, . . . Huayue, W (2019) A photocleavable low molecular weight hydrogel for light-triggered drug delivery. Chin Chem Lett, 30(2), 485–488

  • Ma R, Shi L (2021) Trade-off effect of polymeric nano-medicine in anti-cancer drug delivery. Giant 8:100074

    Article  CAS  Google Scholar 

  • Mahmoud K, Swidan S, El-Nabarawi M, Teaima M (2022) Lipid based nanoparticles as a novel treatment modality for hepatocellular carcinoma: a comprehensive review on targeting and recent advances. J Nanobiotechnol 20(1):109

    Article  CAS  Google Scholar 

  • Mandal B, Bhattacharjee H, Mittal N, Sah H, Balabathula P, Thoma LA, Wood GC (2013) Core–shell-type lipid–polymer hybrid nanoparticles as a drug delivery platform. Nanomed Nanotechnol Biol Med 9(4):474–491

    Article  CAS  Google Scholar 

  • Marcos M, Martin-Rapun R, Omenat A, Serrano JL (2007) Highly congested liquid crystal structures: dendrimers, dendrons, dendronized and hyperbranched polymers. Chem Soc Rev 36(12):1889–1901

    Article  CAS  PubMed  Google Scholar 

  • Metzeler K (2009) Cytarabine/mitoxantrone idiopathic hyperammonaemia leading to coma. Reactions 1257:20

    Google Scholar 

  • Mhlwatika Z, Aderibigbe BA (2018) Polymeric nanocarriers for the delivery of antimalarials. Molecules 23(10):2527

    Article  PubMed  PubMed Central  Google Scholar 

  • Miguel RDA, Hirata AS, Jimenez PC, Lopes LB, Costa-Lotufo LV (2022) Beyond formulation: contributions of nanotechnology for translation of anticancer natural products into new drugs. Pharmaceutics 14(8):1722

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mintzer MA, Grinstaff MW (2011) Biomedical applications of dendrimers: a tutorial. Chem Soc Rev 40(1):173–190

    Article  CAS  PubMed  Google Scholar 

  • Momparler RL (2013) Optimization of cytarabine (ARA-C) therapy for acute myeloid leukemia. Exp Hematol Oncol 2:1–5

    Article  Google Scholar 

  • Mori, T, Yamazaki, R, Nakazato, T, Aisa, Y, Enoki, S, Arai, M, . . . Okamoto, S (2006) Excretion of cytosine arabinoside in saliva after its administration at high doses. Anti-cancer Drugs, 17(5), 597–598

  • Mukherjee A, Waters AK, Kalyan P, Achrol AS, Kesari S, Yenugonda VM (2019) Lipid–polymer hybrid nanoparticles as a next-generation drug delivery platform: state of the art, emerging technologies, and perspectives. Int J Nanomed 14:1937–1952. https://doi.org/10.2147/IJN.S198353

    Article  CAS  Google Scholar 

  • Mulik R, Kulkarni V, Murthy R (2009) Chitosan-based thermosensitive hydrogel containing liposomes for sustained delivery of cytarabine. Drug Dev Ind Pharm 35(1):49–56. https://doi.org/10.1080/03639040802178144

    Article  CAS  PubMed  Google Scholar 

  • Müller R, Petersen R, Hommoss A, Pardeike J (2007) Nanostructured lipid carriers (NLC) in cosmetic dermal products. Adv Drug Deliv Rev 59(6):522–530

    Article  PubMed  Google Scholar 

  • Naseri N, Valizadeh H, Zakeri-Milani P (2015) Solid lipid nanoparticles and nanostructured lipid carriers: structure, preparation and application. Adv Pharmaceut Bull 5(3):305

    Article  CAS  Google Scholar 

  • Nasir A, Kausar A, Younus A (2015) A review on preparation, properties and applications of polymeric nanoparticle-based materials. Polym-Plast Technol Eng 54(4):325–341. https://doi.org/10.1080/03602559.2014.958780

    Article  CAS  Google Scholar 

  • Nurgali K, Jagoe RT, Abalo R (2018) Adverse effects of cancer chemotherapy: Anything new to improve tolerance and reduce sequelae?. Front Pharmacol 9:245

  • Paliwal R, Paliwal SR, Kenwat R, Kurmi BD, Sahu MK (2020) Solid lipid nanoparticles: a review on recent perspectives and patents. Expert Opin Ther Pat 30(3):179–194

    Article  CAS  PubMed  Google Scholar 

  • Parodi, A, Kolesova, EP, Voronina, MV, Frolova, AS, Kostyushev, D, Trushina, DB, . . . Zamyatnin Jr, AA (2022) Anticancer nanotherapeutics in clinical trials: the work behind clinical translation of nanomedicine. Int J Mol Sci, 23(21), 13368

  • Parrott J, Holland M (2017) Undetected severe fetal myelosuppression following administration of high-dose cytarabine for acute myeloid leukemia: is more frequent surveillance necessary? Case Rep Obstet Gynecol 1:5. https://doi.org/10.1155/2017/5175629

    Article  Google Scholar 

  • Pasut G, Veronese F (2007) Polymer–drug conjugation, recent achievements and general strategies. Prog Polym Sci 32(8–9):933–961

    Article  CAS  Google Scholar 

  • Phuphanich S, Maria B, Braeckman R, Chamberlain M (2007) A pharmacokinetic study of intra-CSF administered encapsulated cytarabine (DepoCyt®) for the treatment of neoplastic meningitis in patients with leukemia, lymphoma, or solid tumors as part of a phase III study. J Neurooncol 81:201–208

    Article  CAS  PubMed  Google Scholar 

  • Pola R, Janoušková O, Etrych T (2016) The pH-dependent and enzymatic release of cytarabine from hydrophilic polymer conjugates. Physiol Res 65(2):S225–S232

    Article  CAS  PubMed  Google Scholar 

  • Pourmadadi, M, Eshaghi, MM, Ostovar, S, Mohammadi, Z, Sharma, RK, Paiva-Santos, AC, . . . Pandey, S (2023) Innovative nanomaterials for cancer diagnosis, imaging, and therapy: drug delivery applications. J Drug Deliv Sci Technol, 104357

  • Prasanthan P, Kishore N (2021) Self-assemblies of pluronic micelles in partitioning of anticancer drugs and effectiveness of this system towards target protein. RSC Adv 11(36):22057–22069

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pulumati A, Pulumati A, Dwarakanath BS, Verma A, Papineni RV (2023) Technological advancements in cancer diagnostics: improvements and limitations. Cancer Rep 6(2):e1764. https://doi.org/10.1002/cnr2.1764

    Article  Google Scholar 

  • Raj R, Raj PM, Ram A (2016) Preparation and characterization of solid lipid nanoparticles loaded with cytarabine via a micellar composition for leukemia. RSC Adv 6(58):53578–53586. https://doi.org/10.1039/C6RA10111A

    Article  CAS  Google Scholar 

  • Rajagopal P, Jayandharan GR, Krishnan UM (2021) Evaluation of the anticancer activity of pH-sensitive polyketal nanoparticles for acute myeloid leukemia. Mol Pharm 18(5):2015–2031. https://doi.org/10.1021/acs.molpharmaceut.0c01243

    Article  CAS  PubMed  Google Scholar 

  • Robak T, Wierzbowska A (2009) Current and emerging therapies for acute myeloid leukemia. Clin Ther 31:2349–2370

    Article  CAS  PubMed  Google Scholar 

  • Rostami E, Kashanian S, Azandaryani AH, Faramarzi H, Dolatabadi JEN, Omidfar K (2014) Drug targeting using solid lipid nanoparticles. Chem Phys Lipid 181:56–61

    Article  CAS  Google Scholar 

  • Ruckmani K, Sivakumar M, Kumar SS (2007) Nanoparticular drug delivery system of cytarabine hydrochloride (CTH) for improved treatment of lymphoma. J Biomed Nanotechnol 3(1):90–96. https://doi.org/10.1166/jbn.2007.016

    Article  CAS  Google Scholar 

  • Salvi, L, Dubey, CK, Sharma, K, Nagar, D, Meghani, M, Goyal, S, . . . Sharma, A (2020) A synthesis, properties and application as a possible drug delivery systems dendrimers–a review. Asian J Pharmaceut Res Develop, 8(2), 107–113

  • Serdjebi C, Milano G, Ciccolini J (2015) Role of cytidine deaminase in toxicity and efficacy of nucleosidic analogs. Expert Opin Drug Metab Toxicol 11(5):665–672

    Article  CAS  PubMed  Google Scholar 

  • Siegel RL, Miller KD, Wagle NS, Jemal A (2023) Cancer statistics, 2023. CA: A cancer J Clin 73(1):17–48. https://doi.org/10.3322/caac.21763

    Article  Google Scholar 

  • Singh TA, Das J, Sil PC (2020) Zinc oxide nanoparticles: a comprehensive review on its synthesis, anticancer and drug delivery applications as well as health risks. Adv Coll Interface Sci 286:102317

    Article  CAS  Google Scholar 

  • Suhail M, Rosenholm JM, Minhas MU, Badshah SF, Naeem A, Khan KU, Fahad M (2019) Nanogels as drug-delivery systems: a comprehensive overview. Ther Deliv 10(11):697–717

    Article  CAS  PubMed  Google Scholar 

  • Suzuki, K, Nakazato, T, Sanada, Y, Mihara, A, Tachikawa, N, Kurai, H, . . . Kakimoto, T (2010) Successful treatment with hyper-CVAD and highly active anti-retroviral therapy (HAART) for AIDS-related Burkitt lymphoma. [Rinsho Ketsueki] The Japan J Clin Hematol, 51(3), 207–212

  • Szulc A, Pulaski L, Appelhans D, Voit B, Klajnert-Maculewicz B (2016) Sugar-modified poly (propylene imine) dendrimers as drug delivery agents for cytarabine to overcome drug resistance. Int J Pharm 513(1–2):572–583

    Article  CAS  PubMed  Google Scholar 

  • Tahir, N, Haseeb, MT, Madni, A, Parveen, F, Khan, MM, Khan, S, . . . Khan, A (2019) Lipid polymer hybrid nanoparticles: a novel approach for drug delivery. Role Novel Drug Deliv Vehicles Nanobiomed, 59

  • Talluri SV, Kuppusamy G, Karri VVSR, Tummala S, Madhunapantula SV (2016) Lipid-based nanocarriers for breast cancer treatment–comprehensive review. Drug Delivery 23(4):1291–1305

    Article  CAS  PubMed  Google Scholar 

  • Vangijzegem T, Stanicki D, Laurent S (2019) Magnetic iron oxide nanoparticles for drug delivery: applications and characteristics. Expert Opin Drug Deliv 16(1):69–78

    Article  CAS  PubMed  Google Scholar 

  • Vardanyan, R, Hruby, V (2006) Synthesis of essential drugs: Elsevier. https://doi.org/10.1016/B978-044452166-8/50036-4

  • Vijayan, V, Uthaman, S, Park, I-K (2018) Cell membrane coated nanoparticles: an emerging biomimetic nanoplatform for targeted bioimaging and therapy. Biomim Med Mater, 45–59. https://doi.org/10.1007/978-981-13-0445-3_3

  • Wacker M (2013) Nanocarriers for intravenous injection—the long hard road to the market. Int J Pharm 457(1):50–62

    Article  CAS  PubMed  Google Scholar 

  • Wang J, Yin C, Tang G, Lin X, Wu Q (2013) Synthesis, characterization, and in vitro evaluation of two synergistic anticancer drug-containing hepatoma-targeting micelles formed from amphiphilic random copolymer. Biomater Sci 1(7):774–782

    Article  CAS  PubMed  Google Scholar 

  • Wróbel K, Deręgowska A, Betlej G, Walczak M, Wnuk M, Lewińska A, Wołowiec S (2023) Cytarabine and dexamethasone-PAMAM dendrimer di-conjugate sensitizes human acute myeloid leukemia cells to apoptotic cell death. J Drug Deliv Sci Technol 81:104242

    Article  Google Scholar 

  • Xing H, Hwang K, Lu Y (2016) Recent developments of liposomes as nanocarriers for theranostic applications. Theranostics 6(9):1336

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yadav KS, Sawant KK (2010) Modified nanoprecipitation method for preparation of cytarabine-loaded PLGA nanoparticles. AAPS PharmSciTech 11(3):1456–1465. https://doi.org/10.1208/s12249-010-9519-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yadav KS, Jacob S, Sachdeva G, Chuttani K, Mishra AK, Sawant KK (2011) Long circulating PEGylated PLGA nanoparticles of cytarabine for targeting leukemia. J Microencapsul 28(8):729–742

    Article  CAS  PubMed  Google Scholar 

  • Ye M, Zhao Y, Wang Y, Yodsanit N, Xie R, Gong S (2020) pH-responsive polymer–drug conjugate: an effective strategy to combat the antimicrobial resistance. Adv Func Mater 30(39):2002655

    Article  CAS  Google Scholar 

  • Yin C, Li X, Wu Q, Wang J-L, Lin X-F (2010) Multidrug nanoparticles based on novel random copolymer containing cytarabine and fluorodeoxyuridine. J Colloid Interface Sci 349(1):153–158

    Article  CAS  PubMed  Google Scholar 

  • Yoon, JH, Yoon, JY, Park, HJ, Son, MH, Kim, SH, Kim, W, . . . Park, B K (2014) Diffuse cerebral vasospasm with infarct after intrathecal cytarabine in childhood leukemia. Pediatr Int, 56(6), 921–924. https://doi.org/10.1111/ped.12394

  • Zeng, L, Gowda, B, Ahmed, MG, Abourehab, MA, Chen, Z-S, Zhang, C, . . . Kesharwani, P (2023) Advancements in nanoparticle-based treatment approaches for skin cancer therapy. Mol Cancer, 22(1), 1–50

  • Zhang R, Yang J, Zhou Y, Shami PJ, Kopeček J (2016) N-(2-hydroxypropyl) methacrylamide copolymer–drug conjugates for combination chemotherapy of acute myeloid leukemia. Macromol Biosci 16(1):121–128

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors acknowledge Prof. Dr. Naveed Akhtar, Vice Chancellor/Dean, The Islamia University of Bahawalpur for providing research-based facilities.

Author information

Authors and Affiliations

  1. Akson College of Pharmacy, Mirpur University of Science and Technology (MUST), Mirpur, 10250, Azad Kashmir, Pakistan

    Nasrullah Jan & Faiza Nasar

  2. Department of Pharmacy, The University of Chenab, Gujrat, 50700, Punjab, Pakistan

    Nasrullah Jan & Hassan Shah

  3. Department of Pharmaceutics, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, 63100, Punjab, Pakistan

    Safiullah Khan, Asadullah Madni & Ahsan Ali

  4. Cadson College of Pharmacy, Kharian, 50090, Punjab, Pakistan

    Safiullah Khan

  5. Department of Pharmacy, Faculty of Medical and Health Sciences, University of Poonch, Rawalakot, 12350, Azad Kashmir, Pakistan

    Syed Faisal Badshah

  6. College of Pharmacy, Al Ain University, 112612, Abu Dhabi, United Arab Emirates

    Mohammad F. Bostanudin

  7. AAU Health and Biomedical Research Center, Al Ain University, 112612, Abu Dhabi, United Arab Emirates

    Mohammad F. Bostanudin

Authors
  1. Nasrullah Jan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hassan Shah
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Safiullah Khan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Faiza Nasar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Asadullah Madni
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Syed Faisal Badshah
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ahsan Ali
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mohammad F. Bostanudin
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

NJ: conceptualization, project administration, supervision, validation, role, writing—original draft, writing—review and editing. HS: writing—original draft. SK: writing—original draft. FN: software. AM: project administration, visualization. SFB: writing—original draft. AA: data curation. MFB: formal analysis and writing—review and editing. The authors confirm that no paper mill and artificial intelligence was used.

Corresponding author

Correspondence to Nasrullah Jan.

Ethics declarations

Ethical approval

Not applicable.

Competing interests

The authors declare that they have no competing interests or personal relationships that have influence on the work reported in this paper.

Declaration of generative AI and AI-assisted technologies in the writing process

During the preparation of this work, we used ChatGPT to improve the readability and language of the work. After using this tool, we reviewed and edited the content as needed and take full responsibility for the content of the publication.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jan, N., Shah, H., Khan, S. et al. Old drug, new tricks: polymer-based nanoscale systems for effective cytarabine delivery. Naunyn-Schmiedeberg's Arch Pharmacol 397, 3565–3584 (2024). https://doi.org/10.1007/s00210-023-02865-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00210-023-02865-z

Keywords

Search

Navigation