Controlled Drug Delivery Systems Using In Situ Forming Implants

Controlled drug delivery systems based on in situ forming implants offer a versatile platform for achieving sustained and localised therapeutic release from a single administration. These systems typically comprise a polymer solution or suspension that is injected in liquid form and undergoes phase inversion or gelation upon contact with biological fluids. The resulting depot acts as a reservoir, gradually releasing the active pharmaceutical ingredient through a combination of diffusion, polymer degradation and erosion. Commonly employed materials include biodegradable poly(lactide-co-glycolide) (PLGA), polycaprolactone, polyethylene glycol blends and natural proteins such as zein. By tuning polymer composition, solvent type and formulation parameters, researchers can modulate initial burst release, overall duration of delivery and mechanical properties of the implant. Such technologies have been explored for applications ranging from long-acting contraception and antiretroviral prophylaxis to local chemotherapy, hormone replacement and treatment of chronic conditions such as diabetes and osteoporosis. The global significance of in situ forming implants lies in their capacity to improve patient compliance, reduce systemic side effects and enable precision dosing in diverse anatomical sites.

Research from Nature Portfolio

Recent studies have described an ultra-long-acting biodegradable implant capable of co-delivering multiple antiretroviral agents for up to one year. This formulation utilises a polymer matrix that solidifies in situ and can be removed if adverse effects arise, offering both sustained prophylaxis and a safety mechanism to terminate therapy. Drug solubility in the polymer solvent, matrix porosity and polymer molecular weight were systematically optimised to achieve plasma concentrations above inhibitory thresholds throughout the treatment period. Another investigation explored a PLGA-reinforced polyethylene glycol in situ gel for the depot administration of an oral antidiabetic drug. By adjusting polymer ratios and co-solvent composition, the initial burst was minimised and glycaemic control was maintained in diabetic animal models for two weeks after a single injection, demonstrating the potential of phase-inverting gels in metabolic disease management.

Controlled Drug Delivery Systems Using In Situ Forming Implants publication trend

The graph below shows the total number of articles in controlled drug delivery systems using in situ forming implants across all publications each year (not limited to Nature Index journals).

Technical terms

In situ forming implant: An injectable formulation that transitions from liquid to solid or semi-solid at the administration site, creating a drug-loaded depot.

Phase inversion: The process by which a polymer solution precipitates into a solid matrix upon exchange of solvent with an aqueous environment.

Burst release: The rapid initial release of a significant portion of drug load immediately following implant formation.

Poly(lactide-co-glycolide) (PLGA): A biocompatible, biodegradable copolymer widely used as a matrix former in controlled-release implants.

LogP: The logarithm of the octanol–water partition coefficient, indicating a compound’s hydrophobicity, which influences its diffusion and release rate.

References

1. Ultra-long-acting tunable biodegradable and removable controlled release implants for drug delivery. Nature Communications (2019).
2. A PLGA-reinforced PEG in situ gel formulation for improved sustainability of hypoglycaemic activity of glimepiride in streptozotocin-induced diabetic rats. Scientific Reports (2017).
3. Numerical Mechanistic Modelling of Drug Release from Solvent-Removal Zein-Based In Situ Gel. Pharmaceutics (2023).
4. Effects of Drug Physicochemical Properties on In-Situ Forming Implant Polymer Degradation and Drug Release Kinetics. Pharmaceutics (2022).
5. Investigation of Alogliptin-Loaded In Situ Gel Implants by 23 Factorial Design with Glycemic Assessment in Rats. Pharmaceutics (2022).