Improving the Stability of Transfersome Systems by Co-Encapsulating Components of Varying Hydrophobicity

Background: As a novel drug delivery vehicle, transfersomes (TFSs) have great deformability, good biocompatibility, and biodegradability, which can significantly improve drug delivery efficiency. However, their application is limited by their poor stability and vulnerability to leaks. Methods: This paper prepared and assessed the stability of transfersomes co-loaded with Pueraria total flavonoids (PTFs) and tanshinone (TAN), known as PTF/TAN-TFSs, in order to overcome this constraint. Results: The findings showed that the co-loaded system (PTF/TAN-TFSs) had better structural stability than the single-loaded systems (PTF-TFSs and TAN-TFSs), with drug leakage rates decreased by roughly 5% and 7%, respectively, and a more uniform size distribution with a particle size of 44.52 ± 0.47 nm and a PDI of 0.22, while the single-loaded systems had PDI values larger than 0.3. The co-loaded system showed a better sustained-release profile than the suspension with a 15.28% decrease in the maximum cumulative release of the poorly soluble component Tan IIA. Additionally, the co-loaded system demonstrated enhanced solubilization capability, making the poorly soluble component TAN more soluble by 89.52 times compared to the free medication and by 1.97 times compared to the single-loaded system. Furthermore, the co-loaded system significantly improved the intestinal absorption of Tan IIA, increasing the Papp and Ka values in the ileum segment by 2.02-fold and 1.80-fold, respectively. Conclusions: The stability of the system was successfully improved by co-loading many components with varying hydrophobicities. This method provides a fresh way to enhance transferosome stability, broadening their application in the field of drug delivery.