Modulation of reticuloendothelial activity with liposomes.

Area of Science:

• Pharmacology
• Immunology
• Materials Science

Background:

• The reticuloendothelial system (RES) plays a crucial role in immune responses and drug clearance.
• Liposomes, including multilamellar vesicles (MLV), are investigated as drug delivery systems.
• Understanding MLV interactions with the RES is vital for optimizing liposomal drug delivery and therapeutic strategies.

Purpose of the Study:

• To investigate the impact of charged and neutral multilamellar vesicles (MLV) on reticuloendothelial (RE) activity in mice.
• To determine the influence of MLV charge (negative, positive, neutral) on RE activity over time.
• To assess the dose-dependent effects of charged MLV on RE activity.

Main Methods:

• Preparation of MLV using dipalmitoyl phosphatidylcholine, cholesterol, and charged agents (dicetyl phosphate for negative, stearylamine for positive) or no charge agent.
• Intravenous (i.v.) injection of MLV into mice.
• Measurement of RE activity using the carbon clearance method at various time points post-injection.

Main Results:

• All tested MLV formulations initially caused moderate depression of RE activity (1-4 hours post-injection).
• Negatively charged (dicetyl phosphate) and positively charged (stearylamine) MLV significantly stimulated RES activity at later time points.
• Neutral MLV did not induce significant RES stimulation.
• The stimulation by negatively charged MLV peaked at 48 hours and normalized within 7 days.
• Both depression and enhancement of RE activity by negatively charged MLV were dose-dependent.

Conclusions:

• The charge of multilamellar vesicles significantly influences their interaction with the reticuloendothelial system.
• Charged MLV can modulate RE activity, causing initial depression followed by marked stimulation.
• These findings are important for the application of liposomes as drug carriers and for strategies involving RES blockade.