pH and temperature dual-sensitive liposome gel based on novel cleavable mPEG-Hz-CHEMS polymeric vaginal delivery system

Abstract

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-hydrazonecholesteryl hemisuccinate (mPEG-Hz-CHEMS) polymer was used for vaginal administration. Methods: The pH-sensitive, cleavable mPEG-Hz-CHEMS was designed as a modified pHsensitive 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. Conclusion: 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.

Design of novel multifunctional targeting nano-carrier drug delivery system based on CD44 receptor and tumor microenvironment pH condition

“…Simultaneously, the linker between the oHA and MGK has the proton sponge effect of histidine imidazole group, which can destroy the lysosomal membrane and help the intracellular drugs avoiding destruction. In our previous study (Chen et al, 2010(Chen et al, , 2011(Chen et al, , 2012(Chen et al, , 2013Yu et al, 2013;Chen & Wang, 2014), novel pH-sensitive mPEG-ChitosanKetal (PCK) conjugates were also synthesized and were used to potential pH-sensitive drug delivery system. The similar research was studied in our lab.…”

“…As shown in Figure 6, the tumor volume of the saline control group was excessively enlarged (41000 mm 3 ), while the other groups were much smaller. The Cur-oHMN group suppressed tumor growth most efficiently, followed by the free Cur group (p50.05) (Chen et al, 2010(Chen et al, , 2011(Chen et al, , 2012Yu et al, 2013).…”

“…The powder of Cur-oHMN (containing curcumin 3 mg) and 2 ml PBS (pH 7.4) were put into a dialysis tube. Then, the tube was introduced into 250 ml PBS (0.1 M, pH 7.4 and pH 5.0) containing 0.1% (w/v) Tween 80 with stirring at 120 rpm and 37 C. The 20-mL sample was filtrated and analyzed by HPLC after different time intervals (Chen et al, 2011(Chen et al, , 2012Yu et al, 2013).…”

“…Normal saline and free Cur suspension injected for the control groups. Each individual tumor size was measured with a caliper and the tumor volume was calculated every other day using the following equation: (W 2 Â L)/2, where W is the tumor measurement at the widest point and L is the tumor dimension at the longest point (Chen et al, 2010(Chen et al, , 2011(Chen et al, , 2012Yu et al, 2013).…”

“…Due to the ''Coating Saccharide'' (CD44 clustering) of tumor surface and the slightly acidic condition of tumor, it is difficult to target the chemotherapeutic drugs to the tumor site and achieve satisfying effect for targeting drug. To solve this problem, based on our previous basic work of pH-sensitive nano-carrier (Chen et al, 2010(Chen et al, , 2011(Chen et al, , 2012(Chen et al, , 2013Yu et al, 2013;Chen & Wang, 2014), we will design a multifunctional oHA-histidine (oHA)-menthone 1,2-glycerol ketal (MGK) nano-drug delivery system with CD44 receptor as target. As shown in Figure 1, once oHA-histidine-MGK (oHM) nanoparticles meet the CD44 receptor, the coating of CD44 clustering will not appear.…”