S/O/W microparticles prepared with hydroxyethyl starch-based emulsifier showed reduced macrophage affinity

Area of Science:

• Biomaterials Science
• Drug Delivery
• Pharmacology

Background:

• Intramuscular injection of long-acting microparticles often leads to reduced drug bioavailability due to local macrophage uptake.
• Developing effective drug delivery systems that evade immune clearance is crucial for improving therapeutic outcomes.

Purpose of the Study:

• To investigate the impact of surface modification (hydroxyethyl starch or polyethylene glycol) on ginkgolide B loaded solid lipid microparticles (SLMs).
• To evaluate the influence of surface properties on cellular uptake and systemic drug exposure following intramuscular administration.

Main Methods:

• Ginkgolide B loaded S/O/W SLMs were prepared using melt emulsification and post-insertion.
• Surface modification was achieved using hydroxyethyl starch (HES) or polyethylene glycol (PEG) at varying densities.
• In vitro macrophage uptake (RAW264.7 cells) and in vivo pharmacokinetic studies in rats were conducted.

Main Results:

• Prepared SLMs were spherical with a mean particle size of 10 µm and exhibited controlled release (<10% GB release in 2h).
• HES-modified SLMs demonstrated significantly lower RAW264.7 macrophage uptake compared to PEG-coated SLMs.
• HES-SLMs showed higher systemic drug exposure in rats, indicating reduced cellular uptake and sustained release.

Conclusions:

• Surface modification with HES effectively reduces macrophage uptake of intramuscularly injected microparticles.
• HES-modified SLMs offer improved systemic drug exposure and sustained release, enhancing bioavailability.
• HES-modified SLMs represent a promising strategy for developing advanced intramuscular drug delivery systems.