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.

Breast cancer stem(-like) cells (BCSCs) have been found to be responsible for therapeutic resistance and disease relapse.

In recent years, a number of groups have been investigating the use of “empty” liposomes with no drug loaded as scavengers both for exogenous intoxicants and endogenous toxic molecules. Preclinical trials have demonstrated that repurposing liposomes to sequester such compounds may prove clinically useful. The use of such “empty” liposomes in the dialysate during dialysis avoids recognition by complement surveillance, allowing high doses of liposomes to be used. The “reach” of dialysis may also be increased to molecules that are not traditionally dialysable. We aim to review the current literature in this area with the aims of increasing awareness and informing further research. A structured literature search identified thirteen papers which met the inclusion criteria. Augmenting the extraction of ammonia in hepatic failure with pH-gradient liposomes with acidic centres in peritoneal dialysis is the most studied area, with work progressing toward phase one trials. Liposomes used to augment the removal of exogenous intoxicants and protein-bound uraemic and hepatic toxins that accumulate in these organ failures and liposome-supported enzymatic dialysis have also been studied. It is conceivable that liposomes will be repurposed from the role of pharmaceutical vectors to gain further indications as clinically useful nanomedical antidotes/treatments within the next decade.

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Abstract. Doxorubicin (Dox) has been clinically observed to exert marked anticancer activity. However, it is severely restricted by its associated dose-dependent cardiotoxicity, which may be attenuated by decreasing the cumulative dosage via combining with a non-toxic 'sensitizer'. We previously reported that ocotillol is capable of enhancing the antitumor activity of Dox; however, the effects of ocotillol on its cardiotoxicity remain unclear. In the current study, the effects of ocotillol on the toxicity of Dox were investigated, particularly its role in cardiotoxicity. In the acute injury model, pre-administration of ocotillol prolonged the survival time. In the chronic animal model, pre-administration of ocotillol decreased the elevated levels of plasma creatine kinase (CK) and CK-MB, as well as attenuated the pathological changes that occurred. Pre-treatment with ocotillol ameliorated the decreased glutathione level and reduced the cumulated malondialdehyde in the heart tissue. In addition, pre-treatment with ocotillol restored the lowered white blood cell count. The results indicate that Dox co-treatment with ocotillol may effectively alleviate its associated toxic injury, particularly cardiotoxicity. Thus, co-administration of Dox with ocotillol may be a potential therapeutic strategy.