Designing sub-20 nm self-assembled nanocarriers for small molecule delivery: Interplay among structural geometry, assembly energetics, and cargo release kinetics.

التفاصيل البيبلوغرافية
العنوان:	Designing sub-20 nm self-assembled nanocarriers for small molecule delivery: Interplay among structural geometry, assembly energetics, and cargo release kinetics.
المؤلفون:	Jung BT; Department of Materials Science and Engineering, University of California, Berkeley, 210 Hearst Memorial Mining Building, Berkeley, CA 94720, United States., Lim M; UCB-UCSF Graduate Program in Bioengineering, University of California, Berkeley, 210 Hearst Memorial Mining Building, Berkeley, CA 94720, United States., Jung K; Department of Chemistry, University of California, Berkeley, 210 Hearst Memorial Mining Building, Berkeley, CA 94720, United States., Li M; Department of Chemistry, University of California, Berkeley, 210 Hearst Memorial Mining Building, Berkeley, CA 94720, United States., Dong H; Department of Materials Science and Engineering, University of California, Berkeley, 210 Hearst Memorial Mining Building, Berkeley, CA 94720, United States., Dube N; Department of Materials Science and Engineering, University of California, Berkeley, 210 Hearst Memorial Mining Building, Berkeley, CA 94720, United States., Xu T; Department of Materials Science and Engineering, University of California, Berkeley, 210 Hearst Memorial Mining Building, Berkeley, CA 94720, United States; Department of Chemistry, University of California, Berkeley, 210 Hearst Memorial Mining Building, Berkeley, CA 94720, United States; Material Science Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Rd, Berkeley, CA 94720, United States. Electronic address: tingxu@berkeley.edu.
المصدر:	Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2021 Jan 10; Vol. 329, pp. 538-551. Date of Electronic Publication: 2020 Sep 22.
نوع المنشور:	Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
اللغة:	English
بيانات الدورية:	Publisher: Elsevier Science Publishers Country of Publication: Netherlands NLM ID: 8607908 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-4995 (Electronic) Linking ISSN: 01683659 NLM ISO Abbreviation: J Control Release Subsets: MEDLINE
أسماء مطبوعة:	Original Publication: Amsterdam : Elsevier Science Publishers, 1984-
مواضيع طبية MeSH:	Drug Carriers* , Micelles*, Doxorubicin ; Hydrophobic and Hydrophilic Interactions ; Kinetics
مستخلص:	Biological constraints in diseased tissues have motivated the need for small nanocarriers (10-30 nm) to achieve sufficient vascular extravasation and pervasive tumor penetration. This particle size limit is only an order of magnitude larger than small molecules, such that cargo loading is better described by co-assembly processes rather than simple encapsulation. Understanding the structural, kinetic, and energetic contributions of carrier-cargo co-assembly is thus critical to achieve molecular-level control towards predictable in vivo behavior. These interconnected set of properties were systematically examined using sub-20 nm self-assembled nanocarriers known as three-helix micelles (3HM). Both hydrophobicity and the "geometric packing parameter" dictate small molecule compatibility with 3HM's alkyl tail core. Planar obelisk-like apomorphine and doxorubicin (DOX) molecules intercalated well within the 3HM core and near the core-shell interface, forming an integral component to the co-assembly, as corroborated by small-angle X-ray and neutron-scattering structural studies. DOX promoted crystalline alkyl tail ordering, which significantly increased (+63%) the activation energy of 3HM subunit exchange. Subsequently, 3HM-DOX displayed slow-release kinetics (t 1/2 = 40 h) at physiological temperatures, with ~50× greater cargo preference for the micelle core as described by two drug partitioning coefficients (micellar core/shell K p1 ~ 24, and shell/bulk solvent K p2 ~ 2). The geometric and energetic insights between nanocarrier and their small molecule cargos developed here will aid in broader efforts to deconvolute the interconnected properties of carrier-drug co-assemblies. Adding this knowledge to pharmacological and immunological explorations will expand our understanding of nanomedicine behavior throughout all the physical and in vivo processes they are intended to encounter. (Copyright © 2020 Elsevier B.V. All rights reserved.)
فهرسة مساهمة:	Keywords: Drug delivery; Molecular geometry; Release kinetics; Small molecule encapsulation; Structural characterization; Sub-20 nm nanocarrier
المشرفين على المادة:	0 (Drug Carriers) 0 (Micelles) 80168379AG (Doxorubicin)
تواريخ الأحداث:	Date Created: 20200924 Date Completed: 20210707 Latest Revision: 20210707
رمز التحديث:	20231215
DOI:	10.1016/j.jconrel.2020.09.037
PMID:	32971202
قاعدة البيانات:	MEDLINE

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تدمد:	1873-4995
DOI:	10.1016/j.jconrel.2020.09.037