Transferosome-based transdermal patch system for improved puerarin release

Abstract

A system for the production of puerarin-loaded nano-transferosomes, comprising components for thin-layer hydration, incorporation of an emulsifier and controlled sonication to generate vesicles with improved deformability for transdermal application.

Description

Field of invention

[0001] The invention relates to a system for the transdermal administration of puerarin using nano-transferosomes integrated into a controlled-release transdermal patch. This results in improved permeability and therapeutic bioavailability. Background of the invention

[0002] Transdermal drug delivery has established itself as a promising alternative to oral administration, particularly for drugs with low solubility, limited bioavailability, and poor membrane permeability. Puerarin is a bioactive substance with considerable therapeutic potential; however, its clinical applicability is limited by its hydrophobic nature and its inability to effectively penetrate the skin barrier. Conventional delivery systems do not ensure sustained release, high permeation, or adequate encapsulation of puerarin, resulting in suboptimal therapeutic outcomes. Transferosomes, highly deformable nanovesicles composed of phospholipids and edge activators, offer improved flexibility and penetrate deeper into the skin, thus making them suitable as carriers for difficult-to-transport molecules.However, existing methods for producing transferosomes often exhibit shortcomings in optimization and reproducibility. Therefore, there is a need for an improved system for producing stable, size-controlled transferosomes with high encapsulation efficiency and improved permeation. The integration of such optimized transferosomes into a transdermal patch also enables delayed drug release, improved drug retention, and enhanced therapeutic efficacy. Summary of the invention:

[0003] The invention relates to a system for the production and application of puerarin-loaded nanotransferosomes using a transdermal patch. This system overcomes the limitations associated with puerarin, namely low solubility, low bioavailability, and limited skin permeability. The system comprises an optimized manufacturing module that utilizes thin-layer hydration followed by controlled sonication to produce nanotransferosomes with targeted particle size, polydispersity, and encapsulation efficiency. Optimization using a Box-Behnken experimental design allows for precise adjustment of the drug-lipid ratio, emulsifier concentration, and sonication time to maximize pharmaceutical performance. The optimized nanotransferosomes exhibit high encapsulation efficiency, uniform particle distribution, and stability confirmed by analytical methods.

[0004] The system integrates nano-transferosomes into a transdermal patch matrix produced by solvent extraction. This patch is characterized by high drug content uniformity, mechanical strength, and delayed-release properties. Ex vivo permeation studies confirm that the patch enables significantly improved skin permeation compared to conventional puerarin delivery systems. By combining vesicular deformability and transdermal matrix-controlled release, the invention ensures improved permeation, delayed release, and enhanced therapeutic potential of puerarin. Detailed description

[0005] The system comprises a nano-transferosome preparation unit for the production of puerarin-loaded vesicles via thin-layer hydration. Within this unit, a defined drug-to-lipid ratio is maintained, and emulsifier components are added to increase vesicle flexibility and improve penetration. Hydration is performed under controlled conditions to form the initial vesicle dispersion. To achieve optimal size reduction and homogeneity, the dispersion is treated with ultrasound for a predetermined time. This results in nanoscale transferosomes with improved deformability, suitable for transdermal delivery. Statistical optimization of the system is achieved using a Box-Behnken design, allowing for systematic variation of the drug-to-lipid ratio, emulsifier concentration, and ultrasound treatment time.The model identifies the combination that achieves maximum encapsulation efficiency and the highest drug flow. The optimized formulation shows an encapsulation efficiency of approximately 78.80% and a drug flow of 126.48 µg / cm². 2 / h, indicating effective loading and high skin permeation potential. The resulting transferosomes have a mean particle size of approximately 198 nm with controlled polydispersity, ensuring uniform distribution within the formulation. The compatibility between puerarin and the excipients used in the vesicle system is confirmed by analytical characterization, thus ensuring the stability of the nanovesicles during processing and storage. To ensure extended drug release, the system includes a patch formulation module in which the optimized transferosomes are incorporated into a polymeric transdermal patch via solvent extraction. The resulting patch contains approximately 96% drug, indicating efficient embedding of the vesicles in the matrix.The patch is designed to offer mechanical flexibility, adhesive strength, and controlled, hydration-gated release. In vitro release tests demonstrate sustained release of puerarin for up to 24 hours, with the transferosome-loaded patch exhibiting more than twice the release efficiency of the drug-only patch. This performance confirms the patch's ability to deliver controlled release and effectively encapsulate the drug within the nanovesicles.

[0006] Ex vivo permeation studies with skin tissue further demonstrate that the transferosome-based patch achieves significantly higher permeation, with a 2.66-fold increase compared to conventional puerarin patches. This result confirms the improved deformability of the transferosomes and their ability to effectively penetrate the stratum corneum.

[0007] The system ensures that the nano-transferosomes maintain their structural integrity within the patch matrix, thus preserving their release capacity under physiological conditions. The vesicular flexibility allows for deep penetration into the skin while minimizing drug loss, thereby ensuring consistent and predictable drug release.

[0008] The invention thus provides a stable, biocompatible, and effective transdermal application platform for puerarin, thereby overcoming important limitations of conventional formulations. By combining optimized nanovesicular systems with a controlled-release patch, the invention achieves improved stability, sustained release, and increased therapeutic bioavailability.

Claims

[1] A system for the production of puerarin-loaded nano-transferosomes comprising components for thin-layer hydration, incorporation of an emulsifier and controlled sonication to generate vesicles with improved deformability for transdermal application. [2] System according to claim 1, wherein the active ingredient lipid ratio, the emulsifier concentration and the sonication time are optimized by means of a Box-Behnken experimental design to achieve high encapsulation efficiency and high drug flux. [3] System according to claim 1, wherein the manufactured nano-transferosomes have a controlled particle size, a uniform polydispersity and a stable drug-excipient compatibility that enables delayed release. [4] A transdermal patch system with the optimized nano-transferosomes according to claim 1, wherein the patch enables improved permeation, delayed release and optimized therapeutic application of puerarin.