Plant-derived exosome-like nanovesicles as programmable bio-organic excipients: a next-generation platform for precision and immuno-silent drug delivery

There is increasing demand for advanced drug delivery systems that improve therapeutic efficacy while minimizing toxicity. Conventional pharmaceutical excipients, though historically considered inert, often exhibit limitations such as immunogenicity, toxicity, poor intracellular delivery, and inadequate functionality for biologics and nucleic acid-based therapies. Recently, plant-derived exosome-like nanovesicles (PDENs) have emerged as promising bio-organic nanomaterials with favourable biocompatibility and delivery potential. This article critically reviews PDENs as programmable bio-organic excipients.

A structured literature review was conducted using PubMed, Scopus, Web of Science, and Google Scholar for studies published from 2010 to 2026. Reports covering isolation, physicochemical properties, engineering strategies, formulation approaches, biological functions, translational challenges, and regulatory aspects of PDENs were analyzed.

PDENs exhibit favorable properties including nanoscale size, lipid bilayer structure, intrinsic biological activity, low immunogenicity in preclinical studies, and favorablebiocompatibility. They demonstrate efficient drug loading, improved formulation stability, enhanced cellular uptake, and the ability to traverse biological barriers. Their performance can be further optimized through surface engineering, hybrid systems, and stimuli-responsive delivery strategies. In addition, PDENs may act as co-therapeutic agents due to their antioxidant, anti-inflammatory, and immunomodulatory effects. However, challenges remain in batch consistency, scalable manufacturing, stability, classification, and quality control.

PDENs represent an evolution from conventional excipients to programmable bio-organic systems integrating drug delivery, targeting, and therapeutic functions. They hold strong promise for precision medicine and nanotherapeutics, but clinical translation requires advances in scalable production, Quality by Design implementation, safety evaluation, and regulatory harmonization.