Enhancing oral delivery of plant-derived vesicles for colitis

Liu, Yuan; Ahumada, Adrian Lankenau; Bayraktar, Emine; Schwartz, Paul M.; Chowdhury, Mamur A.; Shi, Sixiang; Sebastian, Manu; Khant, Htet; Val, Natalia de; Bayram, Nazende Nur; Zhang, Guodong; Vu, Thanh Chung; Jie, Zuliang; Jennings, Nicholas B.; Rodríguez-Aguayo, Cristian; Stur, Elaine; Mangala, Lingegowda S.; Wu, Yangjun; Nagaraju, Supriya; Ermias, Brooke; Li, Chun; López-Berestein, Gabriel; Braam, Janet; Sood, Anil K.

doi:10.1016/j.jconrel.2023.03.056

Cited by 5 publications

(3 citation statements)

References 33 publications

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“…Thereafter, we evaluated the in vivo bioavailability and pharmacodynamic effects of different vesicles. To prevent premature breakage of the hydrazone bond (Figure S28) and drug leakage from vesicles in the gastric acid environment (Figure S29), and to achieve targeted release in the jejunum, drug-loaded vesicles were freeze-dried and subsequently encapsulated in Eudragit L100-55-coated capsules. , The pharmaceutical properties (Table S2), structural characteristics (Figure S30), and membrane protein composition (Figures S31 and S32) of mExos and hybrid vesicles remained stable during the freeze-drying process, suggesting that the current freeze-drying method is suitable for the solidification of these vesicles. Liposomes for comparative research were developed using the same process (Table S3 and Figure S33).…”

Section: Resultsmentioning

confidence: 99%

Milk Exosome–Liposome Hybrid Vesicles with Self-Adapting Surface Properties Overcome the Sequential Absorption Barriers for Oral Delivery of Peptides

Xiao,

Wang,

Liu

et al. 2024

ACS Nano

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Milk exosomes (mExos) have demonstrated significant promise as vehicles for the oral administration of protein and peptide drugs owing to their superior capacity to traverse epithelial barriers. Nevertheless, certain challenges persist due to their intrinsic characteristics, including suboptimal drug loading efficiency, inadequate mucus penetration capability, and susceptibility to membrane protein loss. Herein, a hybrid vesicle with self-adaptive surface properties (mExos@DSPE-Hyd-PMPC) was designed by fusing functionalized liposomes with natural mExos, aiming to overcome the limitations associated with mExos and unlock their full potential in oral peptide delivery. The surface property transformation of mExos@ DSPE-Hyd-PMPC was achieved by introducing a pH-sensitive hydrazone bond between the highly hydrophilic zwitterionic polymer and the phospholipids, utilizing the pH microenvironment on the jejunum surface. In comparison to natural mExos, hybrid vesicles exhibited a 2.4-fold enhancement in the encapsulation efficiency of the semaglutide (SET). The hydrophilic and neutrally charged surfaces of mExos@DSPE-Hyd-PMPC in the jejunal lumen exhibited improved preservation of membrane proteins and efficient traversal of the mucus barrier. Upon reaching the surface of jejunal epithelial cells, the highly retained membrane proteins and positively charged surfaces of the hybrid vesicle efficiently overcame the apical barrier, the intracellular transport barrier, and the basolateral exocytosis barrier. The self-adaptive surface properties of the hybrid vesicle resulted in an oral bioavailability of 8.7% and notably enhanced the pharmacological therapeutic effects. This study successfully addresses some limitations of natural mExos and holds promise for overcoming the sequential absorption barriers associated with the oral delivery of peptides.

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Section: Resultsmentioning

confidence: 99%

Milk Exosome–Liposome Hybrid Vesicles with Self-Adapting Surface Properties Overcome the Sequential Absorption Barriers for Oral Delivery of Peptides

Xiao,

Wang,

Liu

et al. 2024

ACS Nano

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“…Remarkably, PDVLNs demonstrate a unique capability to effectively encapsulate both hydrophilic and hydrophobic drugs, as well as gene therapy agents, thus maintaining stability under the harsh conditions of the gastrointestinal tract in mouse models. Furthermore, PDVLNs can traverse biological barriers to reach target tissues, and they are primarily facilitated by intestinal macrophages and stem cells [66,70].…”

Section: Oral Administrationmentioning

confidence: 99%

Plant-Derived Vesicle-like Nanoparticles: The Next-Generation Drug Delivery Nanoplatforms

Wang,

Xin,

Zhou

et al. 2024

Pharmaceutics

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A wide variety of natural bioactive compounds derived from plants have demonstrated significant clinical relevance in the treatment of various diseases such as cancer, chronic disease, and inflammation. An increasing number of studies have surfaced that give credence to the potential of plant-derived vesicle-like nanoparticles (PDVLNs) as compelling candidates for a drug delivery system (DDS). PDVLNs are cost-effective production, non-toxicity and non-immunogenicity and fascinating bi-ocompatibility. In this review, we attempt to comprehensively review and consolidate the position of PDVLNs as next-generation drug delivery nanoplatforms. We aim to give a quick glance to readers of the current developments of PDVLNs, including their biogenesis, characteristic features, composition, administration routes, advantages, and application. Further, we discuss the advantages and limitations of PDVLNs. We expect that the role of PDVLNs in drug delivery will be significantly enhanced, thus positioning them as the next generation of therapeutic modalities in the foreseeable future.

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“…Vesicles with similarities to mammalian EVs can be generated from plants. These vesicles, which range from 50 to 1000 nanometers in size, are biocompatible, can be taken up by mammalian cells, and remain stable in the human body 16 , 17 . They can be isolated using several techniques; one of the most utilized is represented by physical tissue disruption and juice extraction, followed by differential ultracentrifugation.…”

Section: Introductionmentioning

confidence: 99%

Enhanced plant-derived vesicles for nucleotide delivery for cancer therapy

Corvigno,

Liu,

Bayraktar

et al. 2024

npj Precis. Onc.

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Small RNAs (microRNAs [miRNAs] or small interfering RNAs [siRNAs]) are effective tools for cancer therapy, but many of the existing carriers for their delivery are limited by low bioavailability, insufficient loading, impaired transport across biological barriers, and low delivery into the tumor microenvironment. Extracellular vesicle (EV)–based communication in mammalian and plant systems is important for many physiological and pathological processes, and EVs show promise as carriers for RNA interference molecules. However, some fundamental issues limit their use, such as insufficient cargo loading and low potential for scaling production. Plant-derived vesicles (PDVs) are membrane-coated vesicles released in the apoplastic fluid of plants that contain biomolecules that play a role in several biological mechanisms. Here, we developed an alternative approach to deliver miRNA for cancer therapy using PDVs. We isolated vesicles from watermelon and formulated a hybrid, exosomal, polymeric system in which PDVs were combined with a dendrimer bound to miRNA146 mimic. Third generation PAMAM was chosen due to its high branching structure and versatility for loading molecules of interest. We performed several in vivo experiments to demonstrate the therapeutic efficacy of our compound and explored in vitro biological mechanisms underlying the anti-tumor effects of miRNA146, which are mostly related to its anti-angiogenic activity.

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Enhancing oral delivery of plant-derived vesicles for colitis

Cited by 5 publications

References 33 publications

Milk Exosome–Liposome Hybrid Vesicles with Self-Adapting Surface Properties Overcome the Sequential Absorption Barriers for Oral Delivery of Peptides

Milk Exosome–Liposome Hybrid Vesicles with Self-Adapting Surface Properties Overcome the Sequential Absorption Barriers for Oral Delivery of Peptides

Plant-Derived Vesicle-like Nanoparticles: The Next-Generation Drug Delivery Nanoplatforms

Enhanced plant-derived vesicles for nucleotide delivery for cancer therapy

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