Liposomes encapsulating native and cyclodextrin enclosed paclitaxel: Enhanced loading efficiency and its...

Area of Science:

• Pharmaceutical Nanotechnology
• Drug Delivery Systems
• Cancer Therapeutics

Background:

• Paclitaxel (PTX) exhibits poor aqueous solubility, limiting its therapeutic efficacy.
• Current formulations like Taxol® face challenges with drug loading and pharmacokinetic profiles.
• Cyclodextrin complexation and liposomal encapsulation are strategies to overcome these limitations.

Purpose of the Study:

• To develop an improved drug delivery system for Paclitaxel (PTX) using a combination of cyclodextrin (CD) complexation and liposomes.
• To enhance PTX loading, aqueous solubility, and pharmacokinetic properties.
• To evaluate the efficacy and safety of the novel formulation compared to Taxol®.

Main Methods:

• Paclitaxel was complexed with 2,6-di-O-methylbetacyclodextrin (DMβCD).
• Sterically stabilized, double-loaded, PEGylated liposomes (DLPLs) encapsulating PTX and the PTX-DMβCD complex were prepared.
• Physicochemical characterization, cytotoxicity assays (SKOV3 cells), hemolytic potential, anti-angiogenic assays, and in-vivo pharmacokinetic studies in rats were performed.

Main Results:

• DMβCD complexation increased PTX aqueous solubility by ~3x10^4 folds.
• Prepared DLPLs exhibited a size of 162.8 nm, zeta potential of -5.6 mV, and a 2-fold increase in drug loading (5.8 mol%).
• DLPLs demonstrated significantly lower hemolytic potential, 4.2-fold improved cytotoxicity (IC50), and 1.33-fold reduced wound recovery (anti-angiogenesis) compared to Taxol®.
• In-vivo studies showed improved circulation time, higher plasma concentration, and reduced clearance rate for DLPLs.

Conclusions:

• The combination strategy of DMβCD complexation and PEGylated liposomes effectively improved PTX loading and solubility.
• The developed DLPLs exhibit enhanced efficacy, favorable pharmacokinetics, and reduced toxicity compared to Taxol®.
• This novel DLPL formulation represents a promising alternative for Paclitaxel delivery in cancer therapy.