Cyclodextrin-containing Polymers: Versatile Platforms of Drug Delivery Materials

Overview

Journal J Drug Deliv

Date 2012 Apr 13

PMID 22496980

Citations 21

Authors

Jeremy D Heidel

Thomas Schluep

Affiliations

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Abstract

Nanoparticles are being widely explored as potential therapeutics for numerous applications in medicine and have been shown to significantly improve the circulation, biodistribution, efficacy, and safety profiles of multiple classes of drugs. One leading class of nanoparticles involves the use of linear, cyclodextrin-containing polymers (CDPs). As is discussed in this paper, CDPs can incorporate therapeutic payloads into nanoparticles via covalent attachment of prodrug/drug molecules to the polymer (the basis of the Cyclosert platform) or by noncovalent inclusion of cationic CDPs to anionic, nucleic acid payloads (the basis of the RONDEL platform). For each of these two approaches, we review the relevant molecular architecture and its rationale, discuss the physicochemical and biological properties of these nanoparticles, and detail the progress of leading drug candidates for each that have achieved clinical evaluation. Finally, we look ahead to potential future directions of investigation and product candidates based upon this technology.

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References

Greenwald R, Pendri A, Conover C, Lee C, Choe Y, Gilbert C . Camptothecin-20-PEG ester transport forms: the effect of spacer groups on antitumor activity. Bioorg Med Chem. 1998; 6(5):551-62. DOI: 10.1016/s0968-0896(98)00005-4. View

Gatter K, Brown G, Trowbridge I, Woolston R, Mason D . Transferrin receptors in human tissues: their distribution and possible clinical relevance. J Clin Pathol. 1983; 36(5):539-45. PMC: 498283. DOI: 10.1136/jcp.36.5.539. View

Bartlett D, Davis M . Physicochemical and biological characterization of targeted, nucleic acid-containing nanoparticles. Bioconjug Chem. 2007; 18(2):456-68. PMC: 2517011. DOI: 10.1021/bc0603539. View

Davis M . Design and development of IT-101, a cyclodextrin-containing polymer conjugate of camptothecin. Adv Drug Deliv Rev. 2009; 61(13):1189-92. DOI: 10.1016/j.addr.2009.05.005. View

Young C, Schluep T, Hwang J, Eliasof S . CRLX101 (formerly IT-101)-A Novel Nanopharmaceutical of Camptothecin in Clinical Development. Curr Bioact Compd. 2011; 7(1):8-14. PMC: 3182091. DOI: 10.2174/157340711795163866. View

Heidel J, Yu Z, Liu J, Rele S, Liang Y, Zeidan R . Administration in non-human primates of escalating intravenous doses of targeted nanoparticles containing ribonucleotide reductase subunit M2 siRNA. Proc Natl Acad Sci U S A. 2007; 104(14):5715-21. PMC: 1829492. DOI: 10.1073/pnas.0701458104. View

Veronese F, Pasut G . PEGylation, successful approach to drug delivery. Drug Discov Today. 2005; 10(21):1451-8. DOI: 10.1016/S1359-6446(05)03575-0. View

Heidel J, Liu J, Yen Y, Zhou B, Heale B, Rossi J . Potent siRNA inhibitors of ribonucleotide reductase subunit RRM2 reduce cell proliferation in vitro and in vivo. Clin Cancer Res. 2007; 13(7):2207-15. DOI: 10.1158/1078-0432.CCR-06-2218. View

Reineke T, Davis M . Structural effects of carbohydrate-containing polycations on gene delivery. 2. Charge center type. Bioconjug Chem. 2003; 14(1):255-61. DOI: 10.1021/bc025593c. View

10.

Schluep T, Gunawan P, Ma L, Jensen G, Duringer J, Hinton S . Polymeric tubulysin-peptide nanoparticles with potent antitumor activity. Clin Cancer Res. 2009; 15(1):181-9. DOI: 10.1158/1078-0432.CCR-08-1848. View

11.

Pun S, Davis M . Development of a nonviral gene delivery vehicle for systemic application. Bioconjug Chem. 2002; 13(3):630-9. DOI: 10.1021/bc0155768. View

12.

Dohjima T, Lee N, Li H, Ohno T, Rossi J . Small interfering RNAs expressed from a Pol III promoter suppress the EWS/Fli-1 transcript in an Ewing sarcoma cell line. Mol Ther. 2003; 7(6):811-6. DOI: 10.1016/s1525-0016(03)00101-1. View

13.

Cheng J, Khin K, Davis M . Antitumor activity of beta-cyclodextrin polymer-camptothecin conjugates. Mol Pharm. 2005; 1(3):183-93. DOI: 10.1021/mp049966y. View

14.

Popielarski S, Mishra S, Davis M . Structural effects of carbohydrate-containing polycations on gene delivery. 3. Cyclodextrin type and functionalization. Bioconjug Chem. 2003; 14(3):672-8. DOI: 10.1021/bc034010b. View

15.

Schluep T, Hwang J, Hildebrandt I, Czernin J, Choi C, Alabi C . Pharmacokinetics and tumor dynamics of the nanoparticle IT-101 from PET imaging and tumor histological measurements. Proc Natl Acad Sci U S A. 2009; 106(27):11394-9. PMC: 2703672. DOI: 10.1073/pnas.0905487106. View

16.

Davis M, Brewster M . Cyclodextrin-based pharmaceutics: past, present and future. Nat Rev Drug Discov. 2004; 3(12):1023-35. DOI: 10.1038/nrd1576. View

17.

Gonzalez H, Hwang S, Davis M . New class of polymers for the delivery of macromolecular therapeutics. Bioconjug Chem. 1999; 10(6):1068-74. DOI: 10.1021/bc990072j. View

18.

Hu-Lieskovan S, Heidel J, Bartlett D, Davis M, Triche T . Sequence-specific knockdown of EWS-FLI1 by targeted, nonviral delivery of small interfering RNA inhibits tumor growth in a murine model of metastatic Ewing's sarcoma. Cancer Res. 2005; 65(19):8984-92. DOI: 10.1158/0008-5472.CAN-05-0565. View

19.

Daniels T, Delgado T, Rodriguez J, Helguera G, Penichet M . The transferrin receptor part I: Biology and targeting with cytotoxic antibodies for the treatment of cancer. Clin Immunol. 2006; 121(2):144-58. DOI: 10.1016/j.clim.2006.06.010. View

20.

Bellocq N, Pun S, Jensen G, Davis M . Transferrin-containing, cyclodextrin polymer-based particles for tumor-targeted gene delivery. Bioconjug Chem. 2003; 14(6):1122-32. DOI: 10.1021/bc034125f. View