pH- and cinnamic acid-triggerable dioleoylphophatidylethanolamine liposome bearing polyethyleneimine/palmitic acid mixture

ABSTRACT

pH and cinnamic acid (CA)-triggerable liposome was prepared by stabilizing dioleoylphosphatidylethanolamine (DOPE) bilayer with polyethyleneimine (PEI)/palmitic acid (PA) mixture. PEI/PA mixture was air/water interface-active, possibly due to the formation of PEI/PA salt conjugate. When the weight ratio of DOPE to PEI/PA mixture was 200:1, 100:1, 50:1, and 20:1, the fluorescence quenching degree of calcein loaded in the DOPE/PEI/PA assembly prepared using PBS (10 mM, pH 7.4) was 70.7%, 68.7%, 35.3%, and 14%, respectively, indicating that DOPE could be assembled into liposome at the physiological pH value with the aid of the PEI/PA mixture. The hydrodynamic mean diameter of liposome increased from 289 nm to 702 nm on increasing the weight ratio of the DOPE to PEI/PA mixture, possibly because of the bulky PEI chains. The release degree in 120 seconds at pH 4.5, pH 6.0, pH 7.4, and pH 9.0 was about 85%, 24.1%, 10.1%, and 62.0%, respectively, when the suspension of liposome of which the DOPE to PEI/PA mixture weight ratio was 50:1 (pH 7.4) was injected into the release medium of different pH values. The triggered release upon the acidification (i.e., pH 7.4–4.5) and the alkalization (i.e., pH 7.4–9.0) was possibly because PA and PEI were deionized under acidic and alkali conditions, respectively; thus the salt bridge of PEI/PA conjugate could break down. The DOPE liposome also exhibited CA-triggered release. The release degree in 120 seconds at 25°C was 23.1% and it was higher than the release degree at 50°C, 10.9%, possibly because CA could render PEI chains condensed and assembled under upper the critical solution temperature.

GRAPHICAL ABSTRACT

KEYWORDS:

• Cinnamic acid
• dioleoylphophatidylethanolamine
• palmitic acid
• pH value
• polyethyleneimine
• triggerable liposome

Acknowledgments

Following are the results of a study on the “Leaders in INdustry-university Cooperation” Project, supported by the Ministry of Education, Science & Technology (MEST) and the National Research Foundation of Korea (NRF) (2016).