Two cholesterol derivative-based PEGylated liposomes as drug delivery system, study on pharmacokinetics and drug delivery to retina

Abstract

In this study, two cholesterol derivatives, (4-cholesterocarbonyl-4'-(N,N,N-triethylamine butyloxyl bromide) azobenzene (CAB) and 4-cholesterocarbonyl-4'-(N,N-diethylamine butyloxyl) azobenzene (ACB), one of which is positively charged while the other is neutral, were synthesized and incorporated with phospholipids and cholesterol to form doxorubicin (DOX)-loaded liposomes. PEGylation was achieved by including 1,2-distearoyl-sn-glycero-3-phosphatiylethanol-amine-N-[methoxy-(polyethylene glycol)-2000 (DSPE-PEG2000). Our results showed that PEGylated liposomes displayed significantly improved stability and the drug leakage was decreased compared to the non-PEGylated ones in vitro. The in vivo study with rats also revealed that the pharmacokinetics and circulation half-life of DOX were significantly improved when liposomes were PEGylated (p < 0.05). In particular, the neutral cholesterol derivative ACB played some role in improving liposomes' stability in systemic circulation compared to the conventional PC liposome and the positively charged CAB liposome, with or without PEGylation. In addition, in the case of local drug delivery, the positively charged PEG-liposome not only delivered much more of the drug into the rats' retinas (p < 0.001), but also maintained much longer drug retention time compared to the neutral PEGylated liposomes.

The chemotherapeutic potential of doxorubicin-loaded PEG-b-PLGA nanopolymersomes in mouse breast cancer model

“…The calibration curve was prepared using serial dilutions of DOX in the tissue and sera extracts (concentration: 25-1000 ng/mL) of the control mice [35].…”

A Light-Responsive Self-Assembly Formed by a Cationic Azobenzene Derivative and SDS as a Drug Delivery System

“…The procedures of intravitreal injection and retina separation have been described in our previous study4647. Briefly, 10 μL of free RhB was injected into the left eyes, the right eyes were injected with SDS-RhB or CAB30-RhB (10 μL).…”

“…Therefore, rat retina was chosen to study the local drug delivery efficiency of the CAB/SDS system in this study. In our previous study4647, the cytotoxicity, intracellular delivery process and drug delivery efficiency of the CAB-liposome were fully studied in Bel 7402 cells, NIH 3T3 cells and rat retinas. Hence, we also use the same cell lines and rat retinas to make a comparison of these two drug delivery systems.…”

Soft Interaction in Liposome Nanocarriers for Therapeutic Drug Delivery

“…The physico-chemical properties of nanocarriers, such as size (and morphology) and surface functionality (charge typology, stiffness), are the main parameters that can affect their biological clearance. Different strategies can be adopted to prolong the circulation time, while the relevant mechanisms of stabilization can be exploited to improve colloidal stability in biological media [41,42]. …”