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Stabilization of vasoactive intestinal peptide by lipids
G Gololobov1, Y Noda, S Sherman
1Department of Anesthesiology, University of Nebraska Medical Center, Omaha, USA.
Summary
Phosphatidylglycerol (PG) stabilizes vasoactive intestinal peptide (VIP), preventing its degradation. Liposomal VIP shows significantly increased longevity in vivo, offering a method to overcome rapid peptide breakdown.
Area of Science:
- Biochemistry
- Pharmacology
- Drug Delivery
Background:
- Vasoactive intestinal peptide (VIP) is rapidly degraded, limiting its therapeutic potential.
- Phospholipids can influence peptide conformation and stability.
Purpose of the Study:
- To investigate the effect of phospholipids, specifically phosphatidylglycerol (PG), on VIP stability and cleavage.
- To evaluate the potential of liposomal formulations for enhancing VIP longevity in vitro and in vivo.
Main Methods:
- Circular dichroism spectroscopy to determine VIP conformation.
- Radiometric and HPLC assays to measure VIP cleavage rates.
- Enzyme kinetics (Km, Vmax) to elucidate inhibition mechanisms.
- In vivo studies in mice to assess liposomal VIP longevity.
Main Results:
- Anionic phospholipid PG induced a helical conformation in VIP and inhibited its cleavage by trypsin, antibodies, and spontaneously.
- Neutral lipid phosphatidylcholine had no effect on VIP conformation or cleavage.
- PG's inhibition of antibody-catalyzed cleavage was attributed to decreased VIP affinity (increased Km).
- Liposomal VIP remained undegraded for 8 days at 37°C and exhibited a 5-fold longer lifespan in mice compared to aqueous VIP.
Conclusions:
- Phosphatidylglycerol stabilizes VIP by inducing a helical structure, thereby inhibiting its degradation.
- Liposomal encapsulation significantly enhances VIP stability and in vivo longevity, offering a promising strategy for drug delivery.