Influence of polymer size, liposomal composition, surface charge, and temperature on the permeability of pH-sensitive liposomes containing lipid-anchored poly(2-ethylacrylic acid)

Abstract

Background: Liposomes containing pH-sensitive polymers are promising candidates for the treatment of tumors and localized infection. This study aimed to identify parameters influencing the extent of contents release from poly(ethylacrylic acid) (PEAA) vesicles, focusing on the effects of polymer size, lipid composition, vesicle surface charge, and temperature. Methods: Anchored lipid pH-sensitive PEAA was synthesized using PEAA with a molecular weight of 8.4 kDa. PEAA vesicles were prepared by insertion of the lipid-anchored PEAA into preformed large unilamellar vesicles. The preformed liposomes were manipulated by varying the phosphocholine and cholesterol content, and by adding negative or positive charges to the liposomes. A calcein release assay was used to evaluate the effects of polymer size, liposome composition, surface charge, and temperature on liposomal permeability. Results: The release efficiency of the calcein-entrapped vesicles was found to be dependent on the PEAA polymer size. PEAA vesicles containing a phosphatidylcholine to cholesterol ratio of 60:40 (mol/mol) released more than 80% of their calcein content when the molecular weight of PEAA was larger than 8.4 kDa. Therefore, the same-sized polymer of 8.4 kDa was used for the rest of study. The calcein release potential was found to decrease as the percentage of cholesterol increased and with an increase in the phosphocholine acyl chain length (DMPC . DPPC . DSPC). Negatively charged and neutral vesicles released similar amounts of calcein, whereas positively charged liposomes released a significant amount of their contents. pH-sensitive release was dependent on temperature. Dramatic content release was observed at higher temperatures. Conclusion:The observed synergistic effect of pH and temperature on release of the contents of PEAA vesicles suggests that this pH-sensitive liposome might be a good candidate for intracellular drug delivery in the treatment of tumors or localized infection.

Stimuli‐responsive liposomes for drug delivery

“…In vivo studies showed that conditions present within the large intestine (> pH 7.0) promoted the degradation of the Eudragit S100 films, thus triggering the collapse of the microspheres and release of over 85% of the encapsulated agents (5‐ASAs that are coated with chitosan), compared with <10% release from simulated stomach and small intestine conditions (pH 6.3). In good agreement with previous studies, the release profile in liposomes containing pH‐sensitive poly(ethylacrylic acid) (PEAA) was evaluated and found to be pH and PEAA polymer MW dependent . Maximum calcein release (80%) was achieved at pH 4.5 when the PEAA polymer mass was larger than 8.4 kDa.…”

“…In good agreement with previous studies, the release profile in liposomes containing pH-sensitive poly(ethylacrylic acid) (PEAA) was evaluated and found to be pH and PEAA polymer MW dependent. 40 Maximum calcein release (80%) was achieved at pH 4.5 when the PEAA polymer mass was larger than 8.4 kDa. Lower PEAA polymer masses (1.2, 1.9, and 6.5 kDa) showed lower release profiles (8,35, and 70%) due to insufficient protonation of the carboxylic groups of PEAA that would trigger the conformational collapse.…”

Peptide-Based Stealth Nanoparticles for Targeted and pH-Triggered Delivery

“…Based on this result, we hypothesized that coformulation with lipids could favor self-assembly and stability at low concentrations, with the lipids acting as a "lipid skeleton" that supports the stealth peptide. Concerning the lipid part, our choice of lipid composition was based on the known thermal and mechanical stability of 4:1 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)/cholesterol (Chol) 27 mixtures that can provide stable vesicles. Our optimization of vesicle composition started from the measurement of temperature stability and surface charge of vesicles with different percentages of L1.…”

Prospects for Liposome-Encapsulated Nisin in the Prevention of Dental Caries

“…The effect of charge on lipid behavior is governed by the surface charge density of the liposomes, lipid head groups, and interactions between the encapsulated content and lipid [63,64]. Liposomes composed of charged polar lipids with higher electrical charges are more stable than those composed of neutral polar lipids.…”