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In Situ Forming, Enzyme-Responsive Peptoid-Peptide Hydrogels: An Advanced Long-Acting Injectable Drug Delivery

Sophie M Coulter¹, Sreekanth Pentlavalli¹, Yuming An¹

¹Biofunctional Nanomaterials Group, School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast, Co. Antrim BT9 7BL, N. Ireland.

Journal of the American Chemical Society

|June 26, 2024

Summary

This summary is machine-generated.

This study developed a new injectable hydrogel depot for long-acting drug delivery. The system releases antiretroviral zidovudine (AZT) for 35 days, improving patient adherence and reducing initial drug bursts.

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Area of Science:

Biomaterials Science
Drug Delivery Systems
Nanotechnology

Background:

Long-acting drug delivery systems enhance patient adherence by providing sustained medication release.
Injectable depots offer an alternative to oral regimens, simplifying treatment protocols.

Purpose of the Study:

To develop and validate an optimized in situ forming injectable depot for sustained drug delivery.
To demonstrate the feasibility of a peptoid-peptide formulation for controlled release of low-molecular-weight drugs.

Main Methods:

Formulation of a peptoid-peptide-drug conjugate ((NPhe)₄GGGGk(AZT)y(p)-OH) for subcutaneous injection.
Characterization of hydrogel formation kinetics using oscillatory rheology and structure using small-angle neutron scattering.
Assessment of drug release profile and in vitro protease resistance.

Main Results:

The formulation formed a hydrogel depot in situ within seconds upon subcutaneous injection, triggered by skin phosphatases.
Sustained release of zidovudine (AZT) was achieved for 35 days in Sprague-Dawley rats, maintaining therapeutic concentrations.
The peptoid-peptide structure provided protease resistance and reduced initial drug burst via ester linkage hydrolysis.

Conclusions:

The developed peptoid-peptide injectable depot is a promising platform for long-acting drug delivery.
This system effectively delivers antiretroviral drugs, potentially improving treatment adherence and outcomes.
The formulation's rapid gelation, sustained release, and protease resistance highlight its therapeutic potential.