Academic Journal
Ultrafast in situ forming poly(ethylene glycol)-poly(amido amine) hydrogels with tunable drug release properties via controllable degradation rates.
| Title: | Ultrafast in situ forming poly(ethylene glycol)-poly(amido amine) hydrogels with tunable drug release properties via controllable degradation rates. |
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| Authors: | Buwalda SJ; IBMM, Université de Montpellier, CNRS, ENSCM, Faculté de Pharmacie, 15 Avenue Charles Flahault, BP14491, 34093 Montpellier cedex 5, France. Electronic address: sijtze.buwalda@mines-paristech.fr., Bethry A; IBMM, Université de Montpellier, CNRS, ENSCM, Faculté de Pharmacie, 15 Avenue Charles Flahault, BP14491, 34093 Montpellier cedex 5, France., Hunger S; IBMM, Université de Montpellier, CNRS, ENSCM, Faculté de Pharmacie, 15 Avenue Charles Flahault, BP14491, 34093 Montpellier cedex 5, France., Kandoussi S; IBMM, Université de Montpellier, CNRS, ENSCM, Faculté de Pharmacie, 15 Avenue Charles Flahault, BP14491, 34093 Montpellier cedex 5, France., Coudane J; IBMM, Université de Montpellier, CNRS, ENSCM, Faculté de Pharmacie, 15 Avenue Charles Flahault, BP14491, 34093 Montpellier cedex 5, France., Nottelet B; IBMM, Université de Montpellier, CNRS, ENSCM, Faculté de Pharmacie, 15 Avenue Charles Flahault, BP14491, 34093 Montpellier cedex 5, France. |
| Source: | European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V [Eur J Pharm Biopharm] 2019 Jun; Vol. 139, pp. 232-239. Date of Electronic Publication: 2019 Apr 04. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 9109778 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-3441 (Electronic) Linking ISSN: 09396411 NLM ISO Abbreviation: Eur J Pharm Biopharm Subsets: MEDLINE |
| Imprint Name(s): | Publication: Amsterdam : Elsevier Science Original Publication: Stuttgart : Wissenschaftliche Verlagsgesellschaft, c1991- |
| MeSH Terms: | Drug Liberation*, Dendrimers/*chemistry , Drug Carriers/*chemistry , Hydrogels/*chemistry , Polyethylene Glycols/*chemistry, Animals ; Cell Line ; Dendrimers/toxicity ; Dextrans/administration & dosage ; Dextrans/pharmacokinetics ; Drug Carriers/toxicity ; Drug Compounding/methods ; Drug Stability ; Fibroblasts ; Fluorescein-5-isothiocyanate/administration & dosage ; Fluorescein-5-isothiocyanate/analogs & derivatives ; Fluorescein-5-isothiocyanate/pharmacokinetics ; Hydrogels/toxicity ; Mice ; Polyethylene Glycols/toxicity ; Rheology ; Time Factors ; Toxicity Tests |
| Abstract: | Fast in situ forming, chemically crosslinked hydrogels were prepared by the amidation reaction between N-succinimidyl ester end groups of multi-armed poly(ethylene glycol) (PEG) and amino surface groups of poly(amido amine) (PAMAM) dendrimer generation 2.0. To control the properties of the PEG/PAMAM hydrogels, PEGs were used with different arm numbers (4 or 8) as well as different linkers (amide or ester) between the PEG arms and their terminal N-succinimidyl ester groups. Oscillatory rheology measurements showed that the hydrogels form within seconds after mixing the PEG and PAMAM precursor solutions. The storage moduli increased with crosslink density and reached values up to 2.3 kPa for hydrogels based on 4-armed PEG. Gravimetrical degradation experiments demonstrated that hydrogels with ester linkages between PEG and PAMAM degrade within 2 days, whereas amide-linked hydrogels were stable for several months. The release of two different model drugs (fluorescein isothiocyanate-dextran with molecular weights of 4·10 3 and 2·10 6 g/mol, FITC-DEX4K and FITC-DEX2000K, respectively) from amide-linked hydrogels was characterized by an initial burst followed by diffusion-controlled release, of which the rate depended on the size of the drug. In contrast, the release of FITC-DEX2000K from ester-containing hydrogels was governed mainly by degradation of the hydrogels and could be modulated via the ratio between ester and amide linkages. In vitro cytotoxicity experiments indicated that the PEG/PAMAM hydrogels are non-toxic to mouse fibroblasts. These in situ forming PEG/PAMAM hydrogels can be tuned with a broad range of mechanical, degradation and release properties and therefore hold promise as a platform for the delivery of therapeutic agents. (Copyright © 2019 Elsevier B.V. All rights reserved.) |
| Contributed Indexing: | Keywords: Controlled drug delivery; Hydrogel; In situ formation; Poly(amido amine) dendrimer; Poly(ethylene glycol); Tunable degradation |
| Substance Nomenclature: | 0 (Dendrimers) 0 (Dextrans) 0 (Drug Carriers) 0 (Hydrogels) 0 (PEG-PAMAM) 0 (fluorescein isothiocyanate dextran) 3WJQ0SDW1A (Polyethylene Glycols) I223NX31W9 (Fluorescein-5-isothiocyanate) |
| Entry Date(s): | Date Created: 20190408 Date Completed: 20190829 Latest Revision: 20190829 |
| Update Code: | 20221216 |
| DOI: | 10.1016/j.ejpb.2019.04.006 |
| PMID: | 30954658 |
| Database: | MEDLINE |
| ISSN: | 1873-3441 |
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| DOI: | 10.1016/j.ejpb.2019.04.006 |