Oral delivery of messenger RNA (mRNA) therapeutics holds promise for providing noninvasive and self-administered treatments and vaccinations. However, the harsh conditions of the gastrointestinal (GI) tract pose challenges for the effective delivery of these therapeutics. In a recent study, researchers developed a novel capsule-based device called RNACap, specifically engineered for the oral delivery of liquid mRNA nanoparticle (NP) therapeutics to the intestines. This innovative technology aims to protect mRNA from the acidic stomach environment and facilitate its rapid release into the intestines in response to neutral pH, pressure release, and natural peristalsis, allowing for NP-mediated delivery of mRNA into intestinal cells for in vivo transfection.
The RNACap device was designed to address the limitations of oral mRNA therapeutics by ensuring the protection and targeted delivery of mRNA to the intestines. Through a series of experiments using rat and porcine models, the researchers demonstrated that the RNACap effectively remained intact in the stomach but released its contents once in the intestines. This controlled release mechanism led to the expression of multiple mRNAs, showcasing the therapeutic potential of this innovative approach. In rat colitis models, oral administration of RNACaps loaded with mRNA encoding interleukin-10 (IL-10mRNA NP) resulted in a reduction of proinflammatory cytokine levels in both blood and tissues, effectively alleviating colitis symptoms.
The study further validated the efficacy of the RNACap technology in a large-animal model of swine, where the capsules remained intact in the stomach, disassembled in the intestine, and triggered robust mRNA expression within hours of administration. This successful demonstration in preclinical models highlights the potential of RNACap as a promising platform for the oral delivery of liquid mRNA therapeutics to the GI tract, offering new avenues for treating challenging intestinal diseases and potentially other conditions. By leveraging the engineered capsule technology, researchers have overcome key barriers associated with oral mRNA delivery, paving the way for more accessible and targeted therapies for intestinal disorders.
Key Takeaways:
– Engineered capsule technology, such as RNACap, enables the oral delivery of liquid mRNA therapeutics to the intestines, offering a noninvasive and self-administered treatment approach.
– The controlled release mechanism of RNACap protects mRNA from the harsh conditions of the stomach and facilitates targeted delivery to the intestines for in vivo transfection.
– In preclinical models, oral administration of RNACaps loaded with mRNA encoding interleukin-10 demonstrated therapeutic efficacy in reducing proinflammatory cytokine levels and alleviating colitis symptoms.
– RNACap represents a promising platform for advancing oral mRNA therapeutics, with the potential to revolutionize the treatment of intestinal diseases and other challenging conditions.
Tags: formulation
Read more on pubmed.ncbi.nlm.nih.gov