Milk Exosomes Facilitate Oral Delivery of Drugs against Intestinal Bacterial Infections

Abstract

Biopharmaceutics Classification System (BCS) class II and IV drugs exhibit low solubility and suffer a limitation in oral administration. Exosomes have attracted intensive attention in the efficient delivery of such compounds. However, low gastrointestinal stability and high production cost of exosomes hinder their development as drug carriers. Here, milk exosomes are functionalized with phosphatidylserine and are capable of improving the solubility of BCS class II and IV drugs, resulting in facilitating the oral delivery of the drugs. A natural flavonoid, α-mangostin, is loaded into exosomes (AExo) to enhance the antibacterial efficiency, demonstrated by clearing 99% of bacteria in macrophages. Furthermore, AExo exhibits high mucus penetrability and shows a significant therapeutic efficacy in two animal infection models. Collectively, this work expands the application of exosomes from bovine milk with simple operation and low cost, shedding light on the potential of milk exosomes in improving the solubility of drugs to enhance the efficacy of oral administration.

Gb3-Coated Bovine Milk Exosomes as a Practical Neutralizer for Shiga Toxin

“…Milk exosomes with different payloads can be well absorbed at the gastrointestinal tract, as reported in human and animal studies. , Both intact milk exosomes and exosomes loaded with chemotherapeutic drugs for oral delivery did not cause significant systemic and immunologic toxicity, indicating the excellent safety of milk exosomes in such applications . In addition, bovine milk exosomes have been demonstrated with great potential in oral administration of drugs against intestinal bacterial infections …”

“…17 In addition, bovine milk exosomes have been demonstrated with great potential in oral administration of drugs against intestinal bacterial infections. 19 In this work, considering the particular applicability of bovine milk exosomes in drug delivery and the multivalent effect with relevance to Stx−Gb3 interactions, we coated the membrane surface of bovine milk exosomes with synthetic Gb3 derivative to develop a novel Stx neutralizer, and the resultant Gb3-mExo constructs were shown to be very effective in neutralizing StxB in vitro. In addition to the excellent biocompatibility and storage stability, the constructs were also demonstrated with the promising potential for oral administration.…”

Milk exosomes anchored with hydrophilic and zwitterionic motifs enhance mucus permeability for applications in oral gene delivery

“…6 In previous reports, several drugs, including paclitaxel, insulin, and α-mangostin, were loaded in mExo and exhibited improved bioavailability compared to their freely delivered counterparts. [38][39][40] It is important for mExos as drug carriers to maintain their integrity and reach systemic circulation intact. However, they face two primary challenges via oral administration: degradation in the harsh GI environment and hindered transport while crossing the mucus-epithelial barrier.…”

Endocytosis-mediated redistribution of antibiotics targets intracellular bacteria

“…For instance, chimeric antibiotics containing a macrocycle of polymyxin B exhibit potent activity against major Gramnegative members of multidrug-resistant (MDR) bacterial pathogens and overcome colistin resistance. 10 Furthermore, the reported intracellular delivery approaches such as carrier-mediated delivery systems or cell-penetrating peptides are very effective in intracellular drug delivery, [11][12][13] but they are non-tunable and can result in a specific scope of application, significantly limiting the utility of these carriers as potent tools against intracellular bacterial infections. The encapsulated antibiotics target bacterial colonies hidden in intracellular compartments, which is the critical step in the elimination of intracellular bacteria.…”