Unlocking ginsenosides' therapeutic power with polymer-based delivery systems: current applications and future perspectives

Abstract

Ginsenosides, as the main active ingredient of Panax plants, have been found to have extensive pharmacological activity and clinical therapeutic potential in recent years. However, its inherent physical and chemical properties such as poor solubility and low intestinal permeability result in low bioavailability, severely limiting its clinical application and translation. To address these challenges, polymeric carriers-valued for their excellent biocompatibility, structural tunability, and intelligent response functions-have been engineered to: (i) enhance solubilization via polymer conjugation and amphiphilic micellar encapsulation; (ii) achieve passive (EPR-mediated) and active (ligand-directed) tumor targeting to minimize off-target distribution; and (iii) enable on-demand drug release through pH-, ROS-, temperature-, and enzyme-responsive designs. In this review, we delve into the mechanistic principles and synergistic interactions underlying each functional module within a cohesive, function-centred design roadmap. Finally, we explore emerging interdisciplinary directions-including AI-guided polymer design, logic-gated nanocarriers, and microfluidic personalized fabrication-that promise to accelerate the bench-to-bedside translation of multifunctional ginsenoside therapeutics.

Keywords: artificial intelligence; bioavailability enhancement; drug delivery system design 1. introduction; ginsenosides; polymer-based drug delivery system.

FIGURE 1

The molecular structures of representative ginsenosides of PPD and PPT types.

FIGURE 2

Representative therapeutic applications of various ginsenosides.

FIGURE 3

Representative Natural polymers based-ginsenoside delivery system. (A) Scheme for the preparation of BSA-Rh2 NPs. Reproduced with permission from Singh et al. (2017). Copyright ^© Dove Medical Press Limited.; (B) Scheme for the preparation of HA@GRb1@CS NPs. Reproduced with permission from Du et al. (2024). Copyright ^© Licensee MDPI, Basel, Switzerland. (C) Scheme for the preparation of AG/CS/Rb1 nanocomposite films. Created with BioRender.com.

FIGURE 4

Synthetic polymer–based ginsenoside delivery systems. (A) Self-assembly of compound K (CK)-loaded amphiphilic block-copolymer nanoparticles. Reproduced from Zhang et al. (2018) with permission of Elsevier Ltd. (B) Preparation scheme for CK-PC/DSPE-PEG2000 mixed micelles. Reproduced from Jin et al. (2018) with permission of Dove Medical Press. (C) Schematic of Rg3-PLGA-liposome (Rg3-PLs) fabrication. Reproduced from Nguyen et al. (2024) with permission of The Korean Society of Ginseng.

FIGURE 5

Schematic diagram of ligand modification methods for ginsenoside delivery systems targeting different targets. Created with BioRender.com.

FIGURE 6

Schematic illustration of the ginsenoside loaded electrospun membrane preparation method and application on wound healing. Created with BioRender.com.

FIGURE 7

Schematic illustration of carboxymethyl chitosan–β-cyclodextrin nanogel (CMC-β-CD NG) preparation. Reproduced with permission from Xue et al. (2021), ^© MDPI, Basel, Switzerland.

FIGURE 8

Schematic illustration of the ginsenoside loaded thermol-gel preparation method and application on various diseases. Created with BioRender.com.

FIGURE 9

ROS-responsive polymeric delivery platforms. (A) Self-assembly of PEG-b-PPS into micelles encapsulating hydrophobic ginsenoside Rg3. (B) Dual pH/ROS-responsive LA–Ua–Gly nanoparticles for Rh2 release under acidic and oxidative conditions. Created with BioRender.com.

FIGURE 10

Biomimetic polymeric carriers for ginsenoside delivery. (A) Preparation of platelet membrane/erythrocyte membrane-coated PLGA nanoparticles loaded with Rg1 and PFH (PM/RM@PLGA@PFH) for ultrasound-triggered thrombus targeting. Reproduced from Yang et al. (2023) with permission of Elsevier Ltd. (B) Fabrication of Rg3-PLGA nanoparticles camouflaged with tumor-cell microvesicles (TMVs), illustrating homotypic tumor targeting, TMV-mediated immune activation, and enhanced doxorubicin efficacy against 4T1 breast cancer. Reproduced from Zhang et al. (2024) with permission of the Royal Society of Chemistry.