Often neglected: plga/pla swelling orchestrates drug release: hme implants

Bode, C.; Kranz, H.; Fivez, A.; Siepmann, Florence; Siepmann, Juergen

Document type :

Article dans une revue scientifique: Article original

DOI :

10.1016/j.jconrel.2019.05.039

PMID :

31150749

Permalink :

http://hdl.handle.net/20.500.12210/37038

Title :

Often neglected: plga/pla swelling orchestrates drug release: hme implants

Author(s) :

Bode, C. [Auteur]
Kranz, H. [Auteur]
Fivez, A. [Auteur]
Siepmann, Florence [Auteur]

Advanced Drug Delivery Systems (ADDS) - U1008
Médicaments et biomatériaux à libération contrôlée: mécanismes et optimisation - Advanced Drug Delivery Systems - U 1008 [MBLC - ADDS]
Siepmann, Juergen [Auteur]

Advanced Drug Delivery Systems (ADDS) - U1008
Médicaments et biomatériaux à libération contrôlée: mécanismes et optimisation - Advanced Drug Delivery Systems - U 1008 [MBLC - ADDS]

Journal title :

Journal of controlled release . official journal of the Controlled Release Society

Abbreviated title :

J Control Release

Publication date :

2019-05-28

ISSN :

1873-4995

Keyword(s) :

Diffusion
Dissolution
Drug release mechanism
Implant
Swelling
PLA
PLGA

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Different types of poly(lactic-co-glycolic acid) (PLGA)- and poly(lactic acid) (PLA)-based implants for controlled dexamethasone release were prepared by hot melt extrusion (HME). The lactic acid:glycolic acid ratio was ...
Show more >Different types of poly(lactic-co-glycolic acid) (PLGA)- and poly(lactic acid) (PLA)-based implants for controlled dexamethasone release were prepared by hot melt extrusion (HME). The lactic acid:glycolic acid ratio was varied (50:50, 75:25, 100:0) as well as the drug loading (1-15%). Resomer RG 502H, RG 752H and R 202H (all with -COOH end groups) were studied. The implants were characterized before and after exposure to phosphate buffer pH 7.4 at 37 °C. Interestingly, in all cases polymer swelling seems to play an "orchestrating" role for drug release: At early time points, the amounts of water penetrating into the systems are limited (since the macromolecules are hydrophobic and highly entangled). Consequently, only small amounts of drug can dissolve and the dissolved drug molecules are not sufficiently mobile to diffuse out to a noteworthy extent (negligible dexamethasone release for up to 6 weeks). However, the water that is able to enter the implants at early time points cleaves the polyesters right from the beginning. Due to the newly generated -COOH end groups and decreased chain length, the macromolecules become more and more hydrophilic and less entangled. In addition, water-soluble polymer degradation products build up a steadily increasing osmotic pressure, attracting water into the system. Once a critical polymer molecular weight threshold range (around 8 kDa) is reached, substantial implant swelling starts: The systems' volume increases up to 600-1700% and the water contents exceeds 80-90% (partially approaching 100%). Under these fundamentally altered conditions, significant drug amounts can dissolve and the dissolved drug molecules are sufficiently mobile to diffuse out of the implants: Drug release sets on. In brief, polymer swelling "orchestrates" the involved mass transport phenomena: It enables drug release after a certain lag time by fundamentally changing the conditions for drug dissolution and diffusion. Note that in other types of implants, additional mass transport phenomena might be involved, e.g. no burst release was observed from the investigated, initially non-porous implants.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Collections :

Advanced Drug Delivery Systems (ADDS) - U1008

Submission date :

2021-01-20T15:59:15Z

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