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Development of PEGylated carboxylic acid-modified polyamidoamine dendrimers as bone-targeting carriers for the treatment of bone diseases.
- Source :
-
Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2017 Sep 28; Vol. 262, pp. 10-17. Date of Electronic Publication: 2017 Jul 11. - Publication Year :
- 2017
-
Abstract
- In this study, we aimed to develop a polyethylene glycol (PEG)-conjugated third generation polyamidoamine (PAMAM) dendrimer with multiple carboxylic acids as a bone-targeting carrier for the treatment of bone diseases. We conjugated PAMAM backbones to various carboxylic acids [aspartic acid (Asp), glutamic acid (Glu), succinic acid (Suc), or aconitic acid (Aco)] to obtain four different types of carboxylic acid-modified PAMAMs. PEG was covalently bound to carboxylic acid-modified PAMAMs to obtain PEGylated carboxylic acid-modified PAMAMs. In a tissue distribution study, the amount of <superscript>111</superscript> In-labeled unmodified PAMAM taken up by the bone after intravenous injection in mice was 11.3%. In contrast, the dose of <superscript>111</superscript> In-labeled PEG(5)-Asp-PAMAM, PEG(5)-Glu-PAMAM, PEG(5)-Suc-PAMAM, or PEG(5)-Aco-PAMAM that accumulated in the bone after injection was approximately 46.0, 15.6, 22.6, and 24.5%, respectively. The bone clearance rates of <superscript>111</superscript> In-labeled PEGylated carboxylic acid-modified PAMAMs were proportional to their affinities to hydroxyapatite and Ca <superscript>2+</superscript> . An intra-bone distribution study showed that fluorescein isothiocyanate-labeled PEG(5)-Asp-PAMAM predominantly accumulated on eroded and quiescent surfaces, a pattern associated with the pathogenesis of bone diseases, such as rheumatoid arthritis and osteoporosis. Our findings indicate that PEG(5)-Asp-PAMAM is a promising drug carrier for efficient drug targeting to the bones.<br /> (Copyright © 2017 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Bone Diseases drug therapy
Carboxylic Acids chemistry
Carboxylic Acids pharmacokinetics
Carboxylic Acids therapeutic use
Dendrimers chemistry
Dendrimers pharmacokinetics
Dendrimers therapeutic use
Drug Carriers chemistry
Drug Carriers pharmacokinetics
Drug Carriers therapeutic use
Male
Mice
Polyethylene Glycols chemistry
Polyethylene Glycols pharmacokinetics
Polyethylene Glycols therapeutic use
Bone and Bones metabolism
Carboxylic Acids administration & dosage
Dendrimers administration & dosage
Drug Carriers administration & dosage
Polyethylene Glycols administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1873-4995
- Volume :
- 262
- Database :
- MEDLINE
- Journal :
- Journal of controlled release : official journal of the Controlled Release Society
- Publication Type :
- Academic Journal
- Accession number :
- 28710004
- Full Text :
- https://doi.org/10.1016/j.jconrel.2017.07.018