Preparation, Physicochemical Properties, and In Vitro Toxicity towards Cancer Cells of Novel Types of Arsonoliposomes

Arsonoliposomes (ARSL) are liposomes that incorporate arsonolipids (ARS) in their membranes. They have demonstrated significant toxicity towards cancer cells, while being less toxic towards normal cells. In this study, we sought to investigate the possibility to prepare novel types of arsonoliposomes (ARSL) by incorporating a lipidic derivative of curcumin (TREG) in their membrane, and/or by loading the vesicles with doxorubicin (DOX). The final aim of our studies is to develop novel types of ARSL with improved pharmacokinetics/targeting potential and anticancer activity. TREG was incorporated in ARSL and their integrity during incubation in buffer and serum proteins was studied by monitoring calcein latency. After evaluation of TREG-ARSL stability, the potential to load DOX into ARSL and TREG-ARSL, using the active loading protocol, was studied. Loading was performed at two temperatures (40 °C and 60 °C) and different time periods of co-incubation (of empty vesicles with DOX). Calculation of DOX entrapment efficiency (%) was based on initial and final drug/lipid ratios. The cytotoxic activity of DOX-ARSL was tested towards B16F10 cells (mouse melanoma cells), LLC (Lewis Lung carcinoma cells), and HEK-293 (Human embryonic kidney cells). Results show that TREG-ARSL have slightly larger size but similar surface charge with ARSL and that they are both highly stable during storage at 4 °C for 56 d. Interestingly, the inclusion of TREG in ARSL conferred increased stability to the vesicles towards disruptive effects of serum proteins. The active-loading protocol succeeded to encapsulate high amounts of DOX into ARSL as well as TREG-LIP and TREG-ARSL, while the release profile of DOX from the novel liposome types was similar to that demonstrated by DOX-LIP. The cytotoxicity study results are particularly encouraging, since DOX-ARSL were less toxic towards the (normal) HEK cells compared to the two cancer cell-types. Furthermore, DOX-ARSL demonstrated lower toxicities (at all concentrations tested) for HEK cells, compared to that of the corresponding mixtures of free DOX and empty ARSL, while the opposite was true for the cancer cells (in most cases). The current results justify further in vivo exploitation of DOX-ARSL, as well as TREGARSL as anticancer therapeutic systems.

Grafting of anti-nucleolin aptamer into preformed and remotely loaded liposomes through aptamer-cholesterol post-insertion

A new combination strategy of an active loading and active targeting approach was applied in this work.

Metformin-Encapsulated Liposome Delivery System: An Effective Treatment Approach against Breast Cancer

This study aimed at developing metformin hydrochloride (Met) encapsulated liposomal vesicles for enhanced therapeutic outcomes at reduced doses against breast cancer. Liposomal Met was prepared using thin-film hydration through various loading methods; passive loading, active loading, and drug-loaded lipid film. The drug-loaded film method exhibited maximum entrapment efficiency (~65%) as compared to active loading (~25%) and passive loading (~5%) prepared Met-loaded liposomes. The therapeutic efficacy of these optimized liposomes was evaluated for cellular uptake, cytotoxicity, inhibition of metastatic activity, and apoptosis-inducing activity. Results demonstrated significantly superior activity of positively charged liposomes resulting in reduced IC50 values, minimal cell migration activity, reduced colony formation, and profound apoptosis-induced activity in breast cancer cells as compared to Met. The anti-tumor activity was investigated using a clinically relevant in vitro tumor simulation model, which confirmed enhanced anti-tumorigenic property of liposomal Met over Met itself. To the authors’ knowledge, this is the first report of Met-loaded liposomes for improving the efficacy and therapeutic effect of Met against breast cancer. With the results obtained, it can be speculated that liposomal encapsulation of metformin offers a potentially promising and convenient approach for enhanced efficacy and bioavailability in breast cancer treatment.

Testing Mechanical Properties of Rock Bolt under Different Supports Using Fiber Bragg Grating Technology

: Fiber Bragg grating (FBG) sensors, which can accurately measure strain, can be integrated with rock bolts with small fingerprints. In this paper, according to the force mechanism of prestressed anchor and non-prestressed anchor, different loading modes were designed, named active loading mode and passive loading mode. Then, FBG technology was used to monitor the axial force variation of prestressed anchor and non-prestressed anchor in different loading modes. Based on the test results, it is found that when the anchoring force is relatively small (<35 kN), prestressed anchors need to be tested by active loading mode, and non-prestressed anchors need to be tested by passive loading mode. For the prestressed anchor, the force condition of the bolt-shaft was similar to that of the two-force bar, and the axial force of the bolt-shaft was nearly the same along its entire length. Taking the applied load as the reference, the change rate of the axial force of the bolt-shaft was less than 10%. For non-prestressed anchor, due to the plate, there is a certain area surrounding the plate where the axial force of the bolt-shaft was greatly influenced. With applied loads of less than 15 kN, the change rate of the axial force on FBG1 was greater than 10%. With applied loads of greater than 20 kN, this was less than 10%. In this area, influenced by the plate, the axial force of the bolt-shaft increases, and as the applied load of the pullout test increases, the influence decreases.

Development and Characterization of the Solvent-Assisted Active Loading Technology (SALT) for Liposomal Loading of Poorly Water-Soluble Compounds

A large proportion of pharmaceutical compounds exhibit poor water solubility, impacting their delivery. These compounds can be passively encapsulated in the lipid bilayer of liposomes to improve their water solubility, but the loading capacity and stability are poor, leading to burst drug leakage. The solvent-assisted active loading technology (SALT) was developed to promote active loading of poorly soluble drugs in the liposomal core to improve the encapsulation efficiency and formulation stability. By adding a small volume (~5 vol%) of a water miscible solvent to the liposomal loading mixture, we achieved complete, rapid loading of a range of poorly soluble compounds and attained a high drug-to-lipid ratio with stable drug retention. This led to improvements in the circulation half-life, tolerability, and efficacy profiles. In this mini-review, we summarize our results from three studies demonstrating that SALT is a robust and versatile platform to improve active loading of poorly water-soluble compounds. We have validated SALT as a tool for improving drug solubility, liposomal loading efficiency and retention, stability, palatability, and pharmacokinetics (PK), while retaining the ability of the compounds to exert pharmacological effects.