Formulation and characterization of insulin nanoclusters for a controlled release

Area of Science:

• Biopharmaceutical formulation
• Nanotechnology in drug delivery
• Protein chemistry

Background:

• Biopharmaceuticals face formulation and delivery challenges.
• Nanoclusters (NCs) offer a strategy where the biopharmaceutical acts as both therapeutic and vehicle.
• Developing improved formulations is crucial for biotherapeutics.

Purpose of the Study:

• To formulate insulin nanoclusters (INCs) using a novel crosslinking and desolvation technique.
• To characterize the physical properties and biological activity of the formulated INCs.
• To evaluate the in vivo efficacy and safety of high-dose INC delivery.

Main Methods:

• Insulin was crosslinked using the DTSSP crosslinker.
• Crosslinked insulin underwent desolvation to form nanoclusters.
• INC size and zeta potential were measured.
• Cytotoxicity and biological activity were assessed in vitro.
• In vivo efficacy was evaluated in rats via subcutaneous delivery.

Main Results:

• A new methodology yielded insulin nanoclusters (INCs) with controlled size (198 ± 7 nm) and zeta potential (-39 ± 1 mV).
• Crosslinking and clustering did not induce significant cytotoxicity or alter biological activity compared to free insulin.
• INCs required higher doses for similar blood glucose lowering effects in vivo compared to free insulin.
• Subcutaneous delivery of high INC doses demonstrated prolonged efficacy without lethality in rats.

Conclusions:

• The novel crosslinking and desolvation method provides controlled formulation of insulin nanoclusters.
• Insulin nanoclusters are a viable formulation for high-dose subcutaneous delivery, offering prolonged therapeutic effects.
• This formulation strategy holds potential for improved biopharmaceutical delivery systems.