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Injectable Supramolecular Polymer-Nanoparticle Hydrogels for Cell and Drug Delivery Applications

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Published on: February 7, 2021

Ultra-Long-Term Delivery of Hydrophilic Drugs Using Injectable In Situ Cross-Linked Depots.

Sohyung Lee^1,2,3, Spencer Zhao^2,3, Weihua Jiang⁴

¹Harvard Medical School, Boston, MA, USA.

Biorxiv : the Preprint Server for Biology

|September 10, 2024

Summary

This study introduces a novel injectable drug delivery system for ultra-long-term release of hydrophilic medications over six months. The new platform minimizes initial drug burst and offers improved therapeutic potential for chronic conditions.

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Published on: October 26, 2016

Area of Science:

Biomaterials Science
Drug Delivery Systems
Polymer Chemistry

Background:

Existing long-acting injectables (LAIs) struggle with ultra-long-term release of hydrophilic drugs.
Current platforms like in situ forming implants (ISFI) and microspheres suffer from high burst release and rapid diffusion due to solvent efflux and large pores, respectively.

Purpose of the Study:

To develop a novel injectable platform for ultra-long-term release (over six months) of hydrophilic drugs.
To overcome the limitations of burst release and rapid diffusion seen in current LAI technologies.

Main Methods:

Development of an injectable platform using a methacrylated ultra-low molecular weight polycaprolactone pre-polymer.
Formation of in situ cross-linked depots (ISCD) via a solvent-free process.
In vivo studies in rats to evaluate drug release profiles and compare with ISFI.

Main Results:

The ISCD platform achieved ultra-long-term drug release exceeding six months for various hydrophilic drugs (antiretrovirals, antibiotics, naltrexone) and a hydrophobic drug (tacrolimus).
ISCD demonstrated significantly lower burst release and prolonged drug delivery compared to ISFI in rat models.
The system enabled co-delivery of hydrophilic drug combinations and allowed for tuning of release kinetics and degradation via design parameters.

Conclusions:

The developed ISCD platform represents a breakthrough in achieving ultra-long-term drug delivery for hydrophilic medications.
Pharmacokinetic modeling predicts over six months of drug release in humans, surpassing current LAI capabilities.
The platform's biodegradability, retrievability, and biocompatibility offer significant potential for improving treatment adherence in chronic diseases.