Related Experiment Video
Updated: Jun 14, 2026
09:56
Preparation and Characterization of Lipophilic Doxorubicin Pro-drug Micelles
Published on: August 2, 2016
15.5K
Bis-prodrug cryopreserved lipid nanoparticles with enzymatically triggered release
Cameron Hogarth1, Keith Arnold2, Heba Elkateb1
1Department of Chemistry, University of Liverpool Crown Street Liverpool L69 7ZD UK.
Nanoscale Advances
|January 12, 2026
Summary
We developed stable, cryopreservable lipid nanoparticles (LNPs) for water-soluble drugs using a bis-prodrug strategy. Optimized surfactant ratios ensure excellent redispersibility after freeze-drying, enabling sustained drug release.
Area of Science:
- Nanotechnology
- Pharmaceutics
- Drug Delivery
Background:
- Lipid nanoparticles (LNPs) are key for therapeutic delivery.
- Challenges exist in stabilizing water-soluble drugs within LNPs for long-term storage and effective release.
Purpose of the Study:
- To create a cryopreservable LNP formulation for water-soluble drugs.
- To optimize LNP stability and redispersibility after freeze-drying.
- To achieve sustained, enzyme-responsive release of lamivudine from LNPs.
Main Methods:
- Formulation of LNPs using a hydrophobically modified bis-prodrug of lamivudine.
- Systematic variation of surfactant composition (Brij S20 and Lipoid S100).
- Assessment of colloidal stability, particle size, and polydispersity after freeze-drying and redispersion.
- Enzymatic studies to evaluate drug release kinetics.
Main Results:
- A 50/50 ratio of Brij S20/Lipoid S100 provided optimal redispersibility after freeze-drying.
- The 3:1 prodrug/tricaprin core composition yielded LNPs <150 nm with low polydispersity.
- Enzymatic assays showed slow, sustained conversion of the bis-prodrug to active lamivudine over 9 weeks.
Conclusions:
- A prodrug-based strategy enables the formulation of water-soluble APIs into stable, freeze-dried LNPs.
- Surfactant composition critically influences LNP freeze-drying compatibility.
- This LNP platform facilitates controlled, enzyme-responsive release for small molecule drug delivery.
