Abstract
Hyperbranched polyamidoamines (PAMAM) have been widely investigated for therapeutic applications but their cytotoxicity caused by their cationic charges limited their spreading use in biomedical applications. Zwitterionic chitosan (ZWCs) is a biocompatible, pH sensitive and nontoxic polymer which can be used to reduce cytotoxicity by covering the PAMAM surface. The complex formed from synthesized PAMAM and ZWCs with different ratios was prepared at pH 7.4. Encapsulation of 5-Fluorouracil by these complexes has successfully been established for high efficiency drug delivery. The complex with ratio (3:1) ZWCs/PAMAM had average size ~ 310 nm and negatively charged at neutral pH confirming the ability of the ZWCs to cover PAMAM surface. The encapsulation efficiency ranged between 100 and 72.5% with loading capacity from 5 to 20% for different initial feed drug concentration 5–20 mg/ml. The release profile of ZWC–PAMAM complex showed sustained drug release up to period of 38 h.
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References
Kolhe P, Misra E, Kannan RM et al (2003) Drug complexation, in vitro release and cellular entry of dendrimers and hyperbranched polymers. Int J Pharm 259:143–160. https://doi.org/10.1016/S0378-5173(03)00225-4
Agrawal D (2012) Diagnosis and treatment of colorectal cancer: a review. J Drug Deliv Ther. https://doi.org/10.22270/jddt.v2i3.111
Tiǧli Aydin RS, Pulat M (2012) 5-fluorouracil encapsulated chitosan nanoparticles for pH-stimulated drug delivery: evaluation of controlled release kinetics. J Nanomater. https://doi.org/10.1155/2012/313961
Ma Z, Ma R, Wang X et al (2019) Enzyme and PH responsive 5-flurouracil (5-FU)loaded hydrogels based on olsalazine derivatives for colon-specific drug delivery. Eur Polym J 118:64–70. https://doi.org/10.1016/j.eurpolymj.2019.05.017
Peppas NA, Khare AR (1993) Preparation, structure and diffusional behavior of hydrogels in controlled release. Adv Drug Deliv Rev 11:1–35. https://doi.org/10.1016/0169-409X(93)90025-Y
Berger J, Reist M, Mayer JM et al (2004) Structure and interactions in covalently and ionically crosslinked chitosan hydrogels for biomedical applications. Eur J Pharm Biopharm 57:19–34
Nam K, Watanabe J, Ishihara K (2004) The characteristics of spontaneously forming physically cross-linked hydrogels composed of two water-soluble phospholipid polymers for oral drug delivery carrier I: hydrogel dissolution and insulin release under neutral pH condition. Eur J Pharm Sci 23:261–270. https://doi.org/10.1016/j.ejps.2004.07.012
Moustafine RI, Kabanova TV, Kemenova VA, Van Den Mooter G (2005) Characteristics of interpolyelectrolyte complexes of Eudragit E100 with Eudragit L100. J Control Release 103:191–198. https://doi.org/10.1016/j.jconrel.2004.11.031
Amin A, Ahmed EH, Wickleder C, Adlung M, Hashem A, Ayoub MH, Battisha IK (2019) Phosphosilicate–polyamidoamine hyperbranched polymer–Er 3+ nanocomposite toward planar optical waveguide applications. Polym Compos 40:2029–2038. https://doi.org/10.1002/pc.24984
Liu KC, Yeo Y (2013) Zwitterionic chitosan-polyamidoamine dendrimer complex nanoparticles as a ph-sensitive drug carrier. Mol Pharm 10:1695–1704. https://doi.org/10.1021/mp300522p
Zidan TA, Abdelhamid AE, Zaki EG (2020) N-Aminorhodanine modified chitosan hydrogel for antibacterial and copper ions removal from aqueous solutions. Int J Biol Macromol 158:32–42. https://doi.org/10.1016/j.ijbiomac.2020.04.180
Xu P, Bajaj G, Shugg T et al (2010) Zwitterionic chitosan derivatives for pH-sensitive stealth coating. Biomacromol 11:2352–2358. https://doi.org/10.1021/bm100481r
Abdelhamid AE, Elawady MM, El-Ghaffar MAA et al (2015) Surface modification of reverse osmosis membranes with zwitterionic polymer to reduce biofouling. Water Sci Technol Water Supply 15:999–1010. https://doi.org/10.2166/ws.2015.055
Kim NK, Kim J, Shon DJ et al (2019) Synthesis and characterization of biocompatible copolymers containing plant-based cardanol and zwitterionic groups for antifouling and bactericidal coating applications. Eur Polym J 112:688–695. https://doi.org/10.1016/j.eurpolymj.2018.10.034
Monsalve Y, Sierra L, López BL (2015) Preparation and characterization of succinyl-chitosan nanoparticles for drug delivery. Macromol Symp 354:91–98. https://doi.org/10.1002/masy.201400128
Zheng Y, Li S, Weng Z, Gao C (2015) Hyperbranched polymers: advances from synthesis to applications. Chem Soc Rev 44:4091–4130. https://doi.org/10.1039/c4cs00528g
Şenel M, Çevik E (2012) A novel amperometric hydrogen peroxide biosensor based on pyrrole-PAMAM dendrimer modified gold electrode. Curr Appl Phys 12:1158–1165. https://doi.org/10.1016/j.cap.2012.02.040
Jasmine MJ, Kavitha M, Prasad E (2009) Effect of solvent-controlled aggregation on the intrinsic emission properties of PAMAM dendrimers. J Lumin 129:506–513. https://doi.org/10.1016/j.jlumin.2008.12.005
Jaiswal S, Dutta PK, Kumar S et al (2019) Methyl methacrylate modified chitosan: Synthesis, characterization and application in drug and gene delivery. Carbohydr Polym 211:109–117. https://doi.org/10.1016/j.carbpol.2019.01.104
Stobinski L, Lesiak B, Malolepszy A et al (2014) Graphene oxide and reduced graphene oxide studied by the XRD, TEM and electron spectroscopy methods. J Electron Spectrosc Relat Phenom 195:145–154. https://doi.org/10.1016/j.elspec.2014.07.003
Su P, Wang S, Shi Y, Yang Y (2013) Application of cellulase-polyamidoamine dendrimer-modified silica for microwave-assisted chitosan enzymolysis. Process Biochem 48:614–619. https://doi.org/10.1016/j.procbio.2013.03.007
Tummala S, Satish Kumar MN, Prakash A (2015) Formulation and characterization of 5-Fluorouracil enteric coated nanoparticles for sustained and localized release in treating colorectal cancer. Saudi Pharm J 23:308–314. https://doi.org/10.1016/j.jsps.2014.11.010
Kumar S, Koh J (2012) Physiochemical, optical and biological activity of chitosan-chromone derivative for biomedical applications. Int J Mol Sci 13:6103–6116. https://doi.org/10.3390/ijms13056102
Moghazy RM, Labena A, Husien S et al (2020) Neoteric approach for efficient eco-friendly dye removal and recovery using algal-polymer biosorbent sheets: characterization, factorial design, equilibrium and kinetics. Int J Biol Macromol 157:494–509. https://doi.org/10.1016/j.ijbiomac.2020.04.165
Wang RB, Yuan WZ, Zhu XY (2015) Aggregation-induced emission of non-conjugated poly(amido amine)s: discovering, luminescent mechanism understanding and bioapplication. Chin J Polym Sci (Engl Ed) 33:680–687. https://doi.org/10.1007/s10118-015-1635-x
Niu Y, Qu R, Chen H et al (2014) Synthesis of silica gel supported salicylaldehyde modified PAMAM dendrimers for the effective removal of Hg(II) from aqueous solution. J Hazard Mater 278:267–278. https://doi.org/10.1016/j.jhazmat.2014.06.012
Klaykruayat B, Siralertmukul K, Srikulkit K (2010) Chemical modification of chitosan with cationic hyperbranched dendritic polyamidoamine and its antimicrobial activity on cotton fabric. Carbohydr Polym 80:197–207. https://doi.org/10.1016/j.carbpol.2009.11.013
Qie F, Zhang G, Hou J et al (2012) Extracting genomic DNA of foodstuff by polyamidoamine (PAMAM)-magnetite nanoparticles. Talanta 93:166–171. https://doi.org/10.1016/j.talanta.2012.02.007
Zhang C, Su P, Umar Farooq M et al (2010) Synthesis of polyamidoamine dendrimer-grafted silica with microwave assisted protocol. React Funct Polym 70:129–133. https://doi.org/10.1016/j.reactfunctpolym.2009.11.005
Tsubokawa N, Takayama T (2000) Surface modification of chitosan powder by grafting of `dendrimer-like’ hyperbranched polymer onto the surface. React Funct Polym 43:341–350. https://doi.org/10.1016/S1381-5148(99)00065-6
Hayati B, Maleki A, Najafi F et al (2016) Synthesis and characterization of PAMAM/CNT nanocomposite as a super-capacity adsorbent for heavy metal (Ni2 +, Zn2 +, As3 +, Co2 +) removal from wastewater. J Mol Liq 224:1032–1040. https://doi.org/10.1016/j.molliq.2016.10.053
Moaddab M, Nourmohammadi J, Rezayan AH (2018) Bioactive composite scaffolds of carboxymethyl chitosan-silk fibroin containing chitosan nanoparticles for sustained release of ascorbic acid. Eur Polym J 103:40–50. https://doi.org/10.1016/j.eurpolymj.2018.03.032
Zheng Z, Zhang L, Kong L et al (2009) The behavior of MC3T3-E1 cells on chitosan/poly-L-lysine composite films: effect of nanotopography, surface chemistry, and wettability. J Biomed Mater Res Part A 89:453–465. https://doi.org/10.1002/jbm.a.31979
Jirawutthiwongchai J, Klaharn IY, Hobang N et al (2016) Chitosan-phenylalanine-mPEG nanoparticles: from a single step water-based conjugation to the potential allergen delivery system. Carbohydr Polym 141:41–53. https://doi.org/10.1016/j.carbpol.2015.12.076
Aziz SB, Rasheed MA, Abidin ZHZ (2017) Optical and electrical characteristics of silver ion conducting nanocomposite solid polymer electrolytes based on chitosan. J Electron Mater 46:6119–6130. https://doi.org/10.1007/s11664-017-5515-8
Aziz SB (2017) Morphological and optical characteristics of chitosan(1–x): Cuox (4 ≤ x ≤ 12) based polymer nano-composites: optical dielectric loss as an alternative method for tauc’s model. Nanomaterials 7:444. https://doi.org/10.3390/nano7120444
Zhang Z, Hatta H, Ito T, Nishimoto SI (2005) Synthesis and photochemical properties of photoactivated antitumor prodrugs releasing 5-fluorouracil. Org Biomol Chem 3:592–596. https://doi.org/10.1039/b417734g
Acknowledgements
The authors would like to acknowledge Dr A.P. Filippov, S.V. Valueva and A.A. Kutin; Institute of Macromolecular Compounds, Russian Academy of Sciences for their potential efforts in electron microscopy, Uv-spectroscopy and Dynamic light scattering measurements in this work. Also, the authors would like to acknowledge Science, Technology and Innovation Funding Authority STIFA for its grant No. 26599.
Funding
This research is supported by the grants of Sciences, Technology and innovation Funding Authority (STIFA) No.26599 and the Russian Foundation for Basic Research (RFBR) No.17–53-61026 Egypt a.
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Ahmed, E.H., Abdelhamid, A.E., Vylegzhanina, M.E. et al. Morphological and spectroscopical characterization of hyperbranched polyamidoamine–zwitterionic chitosan-encapsulated 5-FU anticancer drug. Polym. Bull. 79, 137–155 (2022). https://doi.org/10.1007/s00289-020-03495-8
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DOI: https://doi.org/10.1007/s00289-020-03495-8