pH and temperature dual-sensitive liposome gel based on novel cleavable mPEG-Hz-CHEMS polymeric vaginal delivery system.
BACKGROUND
In this study, a pH and temperature dual-sensitive liposome gel based on a novel cleavable hydrazone-based pH-sensitive methoxy polyethylene glycol 2000-hydrazone-cholesteryl hemisuccinate (mPEG-Hz-CHEMS) polymer was used for vaginal administration.


METHODS
The pH-sensitive, cleavable mPEG-Hz-CHEMS was designed as a modified pH-sensitive liposome that would selectively degrade under locally acidic vaginal conditions. The novel pH-sensitive liposome was engineered to form a thermogel at body temperature and to degrade in an acidic environment.


RESULTS
A dual-sensitive liposome gel with a high encapsulation efficiency of arctigenin was formed and improved the solubility of arctigenin characterized by Fourier transform infrared spectroscopy and differential scanning calorimetry. The dual-sensitive liposome gel with a sol-gel transition at body temperature was degraded in a pH-dependent manner, and was stable for a long period of time at neutral and basic pH, but cleavable under acidic conditions (pH 5.0). Arctigenin encapsulated in a dual-sensitive liposome gel was more stable and less toxic than arctigenin loaded into pH-sensitive liposomes. In vitro drug release results indicated that dual-sensitive liposome gels showed constant release of arctigenin over 3 days, but showed sustained release of arctigenin in buffers at pH 7.4 and pH 9.0.


CONCLUSIONS
This research has shed some light on a pH and temperature dual-sensitive liposome gel using a cleavable mPEG-Hz-CHEMS polymer for vaginal delivery.
School of Pharmacy, Yantai University, Yantai, People’s Republic of China.
Daquan
D
Chen
Kaoxiang
K
Sun
Hongjie
H
Mu
Mingtan
M
Tang
Rongcai
R
Liang
Aiping
A
Wang
Shasha
S
Zhou
Haijun
H
Sun
Feng
F
Zhao
Jianwen
J
Yao
Wanhui
W
Liu
D000704:Analysis of Variance; D002152:Calorimetry, Differential Scanning; D002470:Cell Survival / Q000187:drug effects; D002788:Cholesterol Esters / Q000737:chemistry*; D005663:Furans / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D057809:HEK293 Cells; D006801:Humans; D006835:Hydrazones / Q000008:administration & dosage / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D017705:Lignans / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry*; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D044367:Phase Transition; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry*; D013696:Temperature; D014622:Vaginal Creams, Foams, and Jellies / Q000008:administration & dosage / Q000737:chemistry*
D002788:Cholesterol Esters; D005663:Furans; D006835:Hydrazones; D017705:Lignans; D008081:Liposomes; D014622:Vaginal Creams, Foams, and Jellies; D011092:Polyethylene Glycols; C013440:cholesteryl succinate; C071942:arctigenin