AIMS Bioengineering, 2018, 5(2): 106-132. doi: 10.3934/bioeng.2018.2.106

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Chemotherapeutic loading via tailoring of drug-carrier interactions in poly (sialic acid) micelles

1 Department of Bioengineering, College of Engineering, Temple University, 1947 N 12th St, Philadelphia, PA 19122, USA
2 Department of Chemical Engineering, College of Engineering, Villanova University, 800 E. Lancaster Ave., Villanova, PA 19085, USA

New methods in nanoparticle development have aimed to develop customized carriers suited for specific purposes. Micelles, due to their highly tailorable nature, are prime candidates for this customizable methodology. In order to maximize drug loading and tailor release, groups of the micelle core should be carefully selected in order to exploit inherent interactions between the selected drug and the carrier core. Small variations within the composition of these groups can greatly affect micelle characteristics (e.g., size, stability, loading and release). While covalent bonding of drug-to-carrier has enhanced drug loading, drawbacks include inhibited release and altered drug properties. As a result, drug/carrier non-covalent interactions such as hydrophobic attraction, hydrogen bonding and π-π stacking have all garnered great interest, allowing for both enhanced loading as well as bond dissociation to aid in drug release. Just as important, external composition of these micelles should be suited for specific therapeutic applications. Examples include providing stabilization, enhanced circulation times and site-specific targeting. Poly (sialic acid) (PSA), a naturally occurring polysaccharide, has been shown to exhibit all three of these properties yet remains relatively unexplored in the field of micelle-based cancer drug delivery applications. Here, we have grafted various phenyl-terminated alkyl groups (PTAGs) onto the backbone of PSA (PTAG-g-PSA), each selected in order to exploit a specific non-covalent interaction (hydrophobic attraction, hydrogen bonding and π-π stacking) between the PTAG group and the anthracycline chemotherapeutic doxorubicin (DOX) (Figure 1). Upon aqueous self-assembly, these amphiphiles formed micelles which exhibited variation in size, stability, cytotoxicity and DOX loading/release based upon the PTAG selected. For example, PTAGs selected to exploit either hydrogen bonding or π-π stacking loaded in a similar fashion yet varied greatly in release properties. Therefore, the synergistic effect of these small-scale modifications in core groups selected can greatly effect micelle characteristics and result in highly tailorable carriers.
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© 2018 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution Licese (http://creativecommons.org/licenses/by/4.0)

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