Physicochemical Factors That Influence the Biocompatibility of Cationic Liposomes and Their Ability to Deliver DNA to the Nuclei of Ovarian Cancer SK-OV-3 Cells

Cationic liposomes composed of 3-[N-(N’,N’-dimethylaminoethane)-carbamoyl] cholesterol (DC-chol) and dioleoylphosphatidylethanolamine (DOPE) have previously been shown to have applications in gene delivery. Our study aims to explore the effects of inclusion of polyethylene glycol (PEG) and using different molar ratios of DC-chol/DOPE on size, zeta potential, cytotoxicity and DNA delivery of DC-chol/DOPE liposomes. Our results show that PEGylation reduces the cytotoxicity of DC-chol/DOPE liposomes, and, furthermore, PEGylated liposome-DNA lipoplexes are smaller in size and more uniform in size distribution than those that are not PEGylated. Additionally, toxicity against ovarian cancer SKOV-3 cells decreases with the amount of cationic DC-chol present in the formulation; however, decreased delivery of DNA to cellular nuclei is also observed. Transfection with the PEGylated liposomes was successfully demonstrated using plasmid DNA with a known functional outcome. These results offer further insight into physicochemical properties important for cationic liposomes as vehicles for DNA delivery and demonstrate the potential of PEGylated DC-chol/DOPE liposomes as systemic delivery carriers for DNA-mediated ovarian cancer therapy.

Preparation of a PEGylated liposome that co-encapsulates l-arginine and doxorubicin to achieve a synergistic anticancer effect

Strategies that combine chemotherapies with unconventional agents such as nitric oxide (NO) have been shown to enhance cancer therapies.

Optimization of Sterically stabilized liposome using design of experiment approach

Recently, a drug delivery system with controlled and targeted drug release at the tumor sites emerged as an attractive option for improving anticancer therapeutics. Advanced nanotherapeutics must not be limited to nanoscale, but should find their way to target the solid tumor via direct or indirect way. Pegylation on the surface of liposome helps to become liposome as long-circulating and indirect or passive targeting to tumors. The purpose of this study is to develop and optimize the critical process parameters, which play an important role in the quality pegylated liposome. The design of experiment (DoE) was used to study the impact of critical process variables like hydration temperature, extrusion process temperature, ethanol concentration, drug loading temperature, and drug loading time. Pegylated liposome was prepared using the ethanol injection method. Size reduction was achieved using the extrusion method. Drug encapsulation was achieved by a remote loading method using an ammonium phosphate gradient. A fractional factorial design was chosen for the optimization of process variables. Hydration temperature and extrusion process temperature directly impact on the degradation of lipids used in liposome formation. Higher temperature increases the lipid degradation during the process. The concentration of ethanol during the size reduction process inversely affects the particle size of the liposome. Higher the ethanol content lowers the particle size achieved. The temperature during drug loading process directly affects the degradation of the drug while inversely affect the encapsulation property. Stability study indicates that optimized formulation using DoE approach remains stable. The present research confirms the feasibility of developing and optimizing sterically stabilized liposome using DoE approach.

Blood Retention and Antigenicity of Polycarboxybetaine-Modified Liposomes

<div>Zwitterionic polycarboxybetaines (PCBs) have gained attention as alternative stealth polymers whose</div><div>liposomal formulation and protein conjugates were reported not to elicit anti-polymer antibodies. Here, we</div><div>studied the blood retention and antigenicity of liposomes modified with PCBs focusing on their chemical</div><div>structures and doses. We compared PCBs with either 1 or 3 (PCB1 or PCB3) spacer carbons between the</div><div>carboxylate and ammonium groups. PCB3-modified liposomes had a short blood retention, whereas PCB1-</div><div>modified liposomes demonstrated extended blood retention that was somewhat superior to PEGylated liposome.</div><div>This confirmed the excellent non-fouling nature of PCB1 reported previously. Interestingly, PCB1-liposome as</div><div>well as PCB3-liposome elicited specific IgMs toward each PCB. The dose-dependent production of specific</div><div>IgMs to PCB-liposomes was similar to that of PEGylated liposome, i.e., high doses of PCB-liposomes reduced</div><div>the production of specific IgMs, termed immunological tolerance. These results indicate the importance of</div><div>investigating the effect of dose to clarify the existence of antigenicity of stealth polymers</div>

Blood Retention and Antigenicity of Polycarboxybetaine-Modified Liposomes

<div>Zwitterionic polycarboxybetaines (PCBs) have gained attention as alternative stealth polymers whose</div><div>liposomal formulation and protein conjugates were reported not to elicit anti-polymer antibodies. Here, we</div><div>studied the blood retention and antigenicity of liposomes modified with PCBs focusing on their chemical</div><div>structures and doses. We compared PCBs with either 1 or 3 (PCB1 or PCB3) spacer carbons between the</div><div>carboxylate and ammonium groups. PCB3-modified liposomes had a short blood retention, whereas PCB1-</div><div>modified liposomes demonstrated extended blood retention that was somewhat superior to PEGylated liposome.</div><div>This confirmed the excellent non-fouling nature of PCB1 reported previously. Interestingly, PCB1-liposome as</div><div>well as PCB3-liposome elicited specific IgMs toward each PCB. The dose-dependent production of specific</div><div>IgMs to PCB-liposomes was similar to that of PEGylated liposome, i.e., high doses of PCB-liposomes reduced</div><div>the production of specific IgMs, termed immunological tolerance. These results indicate the importance of</div><div>investigating the effect of dose to clarify the existence of antigenicity of stealth polymers</div>

Combination of Cisplatin-Withaferin Based on PEGylated Liposome Nanoparticles as Alternative Therapy for Ovarian Cancer

Ovarian cancer is one of the major health problems in gynecology worldwide. Globocan 2012 data shows that ovarian cancer occurs in 239.000 cases, and is placed fourth as the most malignancy occurred in Indonesia. So far, cisplatin is the most effective therapeutic agent, but the high dosage of administration often caused side effects. A new alternative therapy to overcome the problems by using withaferin-A and nanoparticle PEGylated liposome. WFA has the potential effect to reduce cisplatin resistance but has low bioavailability thus, it needs to be encapsulated. This review’s goal is to depict the potency of withaferin-A, cisplatin, and PEGylated liposome combination as a therapeutic agent to treat ovarian cancer. The combination of Cisplatin-Withaferin PEGylated Liposome is constructed by the modified thin lipid film hydration method then administered orally. This combination suppresses 70-80% of the ovarian cancer cell growth in vivo and inhibits NGFR from binding to TRKA, prevents cell migration as much as 50%. Nano-Cisferin-Liposome, inhibits migration of ovarian cancer cell significantly through ?-catenin signaling through ALDH1 that disturb the spheroid formation, and increase apoptosis event as much 70-80% by increasing ROS production up to 2,5 times. Thus, Nano-Cisferin-Liposome (NCL) has potential as a therapeutic agent for treating ovarian cancer. Keywords: Cisplatin; Ovarian Cancer; PEGylated Liposome; Withaferin A