How do PELN Deliver Drugs?

Plant-derived exosome-like nanovesicles (PELN) are nano-sized vesicles originating from the cell membranes of plants, have attracted much attention in the biomedical field in recent years. They share many similarities in physical and chemical properties with mammalian exosomes, such as biodegradability, biocompatibility, stable structure, cellular membrane-like nature and the ability to encapsulate a wide range of cargo. These vesicles are capable of encapsulating a wide range of drug molecules, including small molecule drugs, proteins, nucleic acids, etc., to achieve targeted delivery through biological barriers, thereby improving drug utilization and efficacy.

Fig. 1. PELNs serve as vectors for drug delivery (Mu N, Li J, et al., 2023).

PELN's Advantages as a Drug Delivery Platform

• Biocompatibility and safety: PELN are generally derived from the parts of plants that have been consuming or using for many years, such as soybeans, corn, tobacco, etc. These plants are highly biocompatible and safe to the human body. Therefore, the current study shows that plant exosomes as drug delivery platforms have no significant effect on physiological and biochemical parameters of experimental animals, and there is a low risk of immune response and toxicity during drug delivery.
• Stability: PELN possess a unique lipid bilayer and surface modifications, which makes them resistant to temperature, pH, simulated physiological environments and sonication. In particular, It can easily endure the harsh gastrointestinal environment, encapsulating the drug and protecting against attack and degradation. This stability is a big advantage in oral drug delivery.
• Targeted delivery: Through specific modifications, such as surface antibodies or receptor ligands, PELN can achieve targeted delivery to specific tissues or cells. These modifications will not only improve the utilisation of the medicines, but also reduce systemic side effects of the applied drug and improve the therapeutic effects.
• Synergistic therapeutic effects: PELN themselves exhibit biological activity, which can synergize with encapsulated drugs. Some contain bioactive substances such as antioxidants and anti-inflammatory agents, which can enhance the efficacy of drugs and promote tissue repair and regeneration.
• Ease of production: Plants are easily sourced, enabling large-scale, cost-effective production of PELN.

Methods of Delivery

• Colon targeting: The colon is a crucial target for drug delivery, especially for treating intestinal diseases and inflammatory bowel diseases. PELN can effectively target the colon, making them suitable for treating conditions like colitis. For example, drugs encapsulated in ginger ELN can enhance drug targeting and increase their local concentration in the colon, thereby reducing systemic side effects. In addition, by adjusting the surface modification and release properties of plant exosomes, precise delivery to different parts of the colon can be achieved.
• Transdermal delivery: Transdermal delivery is a non-invasive and convenient method where drugs penetrate the skin barrier for absorption and local action. The small size and lipid bilayer structure of PELN offer good skin permeability. Through transdermal systems, PELN can deliver drugs deep into the skin, increasing absorption efficiency and therapeutic effect. For instance, aloe-derived ELN not only have antioxidant and pro-repair properties, but also can enter the skin cells through endocytosis mediated by lattice proteins and cytoplasmic membrane microcapsules to realize transdermal delivery of drugs. Cucumber-derived exosome vesicles mixed with lipophilic drug substitutes resulted in a 2-fold increase in skin penetration efficiency. In addition, by adjusting the composition and surface modification of plant exosomes, their transdermal properties can also be optimized to improve the bioavailability of drugs.

Fig. 2. Schematic diagram of PELN transdermal administration (Wang Y, Wei Y, et al., 2023).

• Tumor targeting: Tumor drug delivery is challenging due to the complex tumor microenvironment and vasculature. However, PELN can be modified for targeted delivery to tumors. Lemon ELN can target tumor cells and activate TNF-related apoptosis-inducing ligand to inhibit tumor growth. Furthermore, genetic engineering or metabolic labeling allows for the introduction of targeting molecules such as antibodies or receptor ligands, enabling specific recognition and binding to tumor cells. This targeted delivery not only increases drug utilization but also reduces damage to normal tissues.

Fig. 3. Modification of PELN for targeted drug delivery (Dad HA, Gu TW, et al., 2020).

• Gene delivery: Gene delivery is a pivotal research area in biomedicine, crucial for treating genetic disorders and cancer. PELN serve as carriers for gene delivery due to their unique advantages. By encapsulating nucleic acids such as mRNA and miRNA, PELN achieve in vivo gene delivery and expression. Surface modification techniques using nucleic acid aptamers allow loading specific gene sequences onto PELN for targeted delivery and expression control. Additionally, PELN have low immunogenicity and excellent biocompatibility, reducing immune reactions and toxicity during gene delivery.

As a novel drug delivery platform, PELN offer distinctive advantages and a wide range of applications. By employing methods such as colon targeting, transdermal delivery, tumor targeting, and gene delivery, PELN enable precise drug delivery and efficient therapy. As research into PELN progresses and technology advances, they are expected to play an increasingly important role in drug delivery. Future developments may see more applications of PELN in disease treatment and their integration with other drug delivery technologies. Furthermore, research into the biosafety, production processes, and quality control of PELN is essential to ensure their safety and efficacy in clinical applications.

References

1. Mu N, Li J, et al. Plant-Derived Exosome-Like Nanovesicles: Current Progress and Prospects. Int J Nanomedicine. 2023. 18, 4987-5009.
2. Wang Y, Wei Y, et al. Plant Exosome-like Nanoparticles as Biological Shuttles for Transdermal Drug Delivery. Bioengineering (Basel). 2023. 10(1), 104.
3. Dad HA, Gu TW, et al. Plant Exosome-like Nanovesicles: Emerging Therapeutics and Drug Delivery Nanoplatforms. Mol Ther. 2021. 29(1), 13-31.

For research use only. Not for any other purpose.