Lyophilization enhances the stability of Panax notoginseng total saponins-loaded transfersomes without adverse effects on ex vivo/in vivo skin permeation

by Selleckchem | Jan 13 2024

Transfersomes (TFSs) have been extensively investigated to enhance transdermal drug delivery. As a colloidal dispersion system, TFSs are prone to problems such as particle aggregation and sedimentation, oxidation and decomposition of phospholipids. To enhance the stability of panax notoginseng saponins (PNS)-loaded transfersomes (PNS-TFSs) without adverse influences on their skin permeation, we prepared lyophilized PNS-loaded transfersomes (PNS-FD-TFSs), clarified their physicochemical characteristics and investigated their in vitro drug release, ex vivo skin permeation/deposition and in vivo pharmacokinetics. In this study, a simple, fast and controllable process was developed for preparing lyophilized PNS-TFSs. In the optimized PNS-FD-TFS formulation, sucrose and trehalose were added to the PNS-TFS dispersion with a mass ratio of trehalose, sucrose, and phospholipid of 3:2:1, and the mixture was frozen at -80 °C for 12 h followed by lyophilization at -45 °C and 5 Pa for 24 h. The optimized formulation of PNS-FD-TFSs was screened based on the appearance and reconstitution time of the lyophilized products, vesicle size, and PDI of the freshly reconstituted dispersions. It maintained stable physicochemical properties for at least 6 months at 4 °C. The vesicle size of PNS-FD-TFSs was below 100 nm and homogenous with a polydispersity index of 0.2 after reconstitution. The average encapsulation efficiencies of the five index saponins notoginsenoside R1 (NGR1), ginsenoside Rg1 (GRg1), ginsenoside Re (GRe), ginsenoside Rb1 (GRb1) and ginsenoside Rd (GRd) in PNS-FD-TFSs were 68.41 ± 5.77%, 68.95 ± 6.08%, 65.46 ± 10.95%, 91.50 ± 5.62% and 95.78 ± 1.70%, respectively. The reconstituted dispersions of PNS-FD-TFSs were similar to PNS-TFSs in in vitro release, ex vivo skin permeation, and deposition. The pharmacokinetic studies showed that, compared with the PNS liposomes (PNS-LPS), the PNS-FD-TFS-loaded drug could permeate through the skin and enter the blood rapidly. It can be concluded that the lyophilization process can effectively improve the stability of PNS-TFSs without compromising their transdermal absorption properties.

Comments:

This is an intriguing study focused on enhancing the stability of Panax notoginseng saponins (PNS)-loaded transfersomes (TFSs) without compromising their transdermal absorption properties. Transfersomes, being a colloidal dispersion system, often face challenges like particle aggregation, sedimentation, and lipid degradation. The approach here involves lyophilization to create PNS-loaded transfersomes (PNS-FD-TFSs), aiming to maintain stability while retaining skin permeation capabilities.

The study's methodology seems comprehensive, starting with the addition of sucrose and trehalose to the PNS-TFS dispersion in specific ratios. The freezing and lyophilization process was meticulously controlled, with parameters like temperature and pressure carefully regulated to obtain the desired formulation.

Key findings indicate promising results regarding the stability and characteristics of the optimized PNS-FD-TFSs. These include:

1. **Physicochemical stability:** The formulation maintained stable properties for at least 6 months at 4°C, a critical aspect for pharmaceutical applications.

2. **Particle size and uniformity:** The vesicle size remained below 100 nm with a low polydispersity index (PDI), ensuring homogeneity after reconstitution.

3. **Encapsulation efficiency:** High encapsulation efficiencies were achieved for the saponins, ensuring a substantial amount of the drug remained encapsulated within the transfersomes.

4. **Comparable in vitro and ex vivo performance:** Reconstituted PNS-FD-TFSs exhibited similar behavior to PNS-TFSs in terms of in vitro drug release, ex vivo skin permeation, and deposition.

5. **Enhanced pharmacokinetics:** Compared to PNS liposomes (PNS-LPS), PNS-FD-TFSs showed rapid skin permeation and entry into the bloodstream in pharmacokinetic studies.

The conclusion drawn from this study suggests that the lyophilization process effectively improves the stability of PNS-TFSs without compromising their transdermal absorption properties, making it a promising approach for transdermal drug delivery systems.

This research could have significant implications in pharmaceutical formulation development, particularly in enhancing the stability and efficacy of transdermally delivered drugs like Panax notoginseng saponins.