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Intracochlear PLGA implants for simultaneous controlled release of multiple drugs
P-K Nguyen1, C Olivier1, P Toulemonde1
1Univ. Lille, Inserm, CHU Lille, U1365, F-59000 Lille, France.
Summary
Biodegradable implants deliver multiple drugs to the inner ear, overcoming the blood cochlear barrier. These poly(lactic-co-glycolic acid) implants successfully released dexamethasone and lidocaine in vivo and in vitro.
Area of Science:
- Biomaterials Science
- Drug Delivery Systems
- Otolaryngology
Background:
- The blood cochlear barrier impedes effective drug delivery to the inner ear, a critical challenge for treating hearing loss and related disorders.
- Current treatments lack targeted delivery, leading to systemic side effects and limited efficacy.
Purpose of the Study:
- To develop and characterize miniaturized, biodegradable implants for simultaneous, controlled delivery of dexamethasone, lidocaine, and curcuminoids to the inner ear.
- To evaluate the in vitro and in vivo drug release profiles and biocompatibility of these novel drug delivery systems.
Main Methods:
- Poly(lactic-co-glycolic acid) (PLGA) implants (0.3 mm diameter) were fabricated using hot melt extrusion, incorporating dexamethasone, lidocaine, and curcuminoids.
- Implants were characterized using DSC, X-ray diffraction, GPC, optical microscopy, and TGA. In vitro and in vivo (gerbil cochlea) drug release studies were conducted.
- Local drug concentrations were monitored in vivo, and animal behavior and tissue responses were assessed for biocompatibility.
Main Results:
- Implants demonstrated controlled, simultaneous release of dexamethasone and lidocaine in vitro, with lidocaine releasing faster than dexamethasone.
- In vivo, drug release was accelerated, with complete dexamethasone release within 2 weeks, likely due to polymer degradation.
- Curcuminoids showed limited release due to poor solubility but were visually observed to be released in vivo within 1-2 weeks. No adverse effects were observed in the animals.
Conclusions:
- Miniaturized PLGA implants offer a promising strategy for targeted inner ear drug delivery, overcoming the blood cochlear barrier.
- The implants facilitate simultaneous controlled release of multiple therapeutic agents, with potential applications in treating hearing loss, tinnitus, and vertigo.
- Further research is warranted to optimize curcuminoid delivery and fully elucidate the long-term efficacy and safety of these implants.
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