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Mucoadhesive polymer coating on drugs can provide higher residence time in the gut. These mechanisms include disulfide bonds and ionic interactions with the mucosa
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The systemic pharmacotherapeutic efficacy of immunomodulatory drugs is heavily influenced by its route of administration. A few common routes for the systemic delivery of immunotheraputics are intravenous, intraperitoneal, and intramuscular injections. However, the development of novel biomaterials, in adjunct to current progress in immunoengineeri...
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... Each individual Peyer's patch has its own unique drainage pathway, complete with pre-collectors that lead to the same place that the lacteals do [32]. There is a possibility that the muscular lymphatics that surround the superior portion of Peyer's patches also play a role in medication delivery [33]. They each have their own drainage system, which eventually combines with the mesenteric lymph for onward transit [34]. ...
Oral administration is preferred over other drug delivery methods due to its safety, high patient compliance, ease of ingestion without discomfort, and tolerance of a wide range of medications. However, oral drug delivery is limited by the poor oral bioavailability of many drugs, caused by extreme conditions and absorption challenges in the gastrointestinal tract. This review thoroughly discusses the targeted drug vehicles to the intestinal lymphatic system (ILS). It explores the structure and physiological barriers of the ILS, highlighting its significance in dietary lipid and medication absorption and transport. The review presents various approaches to targeting the ILS using spatially precise vehicles, aiming to enhance bioavailability, achieve targeted delivery, and reduce first-pass metabolism with serve in clinic. Furthermore, the review outlines several methods for leveraging these vehicles to open the ILS window, paving the way for potential clinical applications in cancer treatment and oral vaccine delivery. By focusing on targeted drug vehicles to the ILS, this article emphasizes the critical role of these strategies in improving therapeutic efficacy and patient outcomes. Overall, this article emphasizes the critical role of targeted drug vehicles to the ILS and the potential impact of these strategies on improving therapeutic efficacy and patient outcomes.
... The immune responses are mainly initiated in the intestine, where the majority of vaccine uptake and drug absorption occur [167,168]. The intestine consists of several layers, including the mucus layer, water layer, epithelial layer, basement membrane/Peyer's patches, and lymph nodes [169]. The epithelial layer is composed of enterocytes, goblet cells, and microfold cells (M cells), which are joined together by tight junctions that prevent the movement of molecules through paracellular and transcellular routes [169][170][171]. ...
... The intestine consists of several layers, including the mucus layer, water layer, epithelial layer, basement membrane/Peyer's patches, and lymph nodes [169]. The epithelial layer is composed of enterocytes, goblet cells, and microfold cells (M cells), which are joined together by tight junctions that prevent the movement of molecules through paracellular and transcellular routes [169][170][171]. Enterocytes, the most abundant cells in the intestinal epithelium (constituting up to 80% of the local cell population), transport antibodies through transcytosis using the neonatal Fc receptor (FcRn) and form antibody-antigen complexes [172,173]. ...
Given the limitations of conventional invasive vaccines, such as the requirement for a cold chain system and trained personnel, needle-based injuries, and limited immunogenicity, non-invasive vaccines have gained significant attention. Although numerous approaches for formulating and administrating non-invasive vaccines have emerged, each of them faces its own challenges associated with vaccine bioavailability, toxicity, and other issues. To overcome such limitations, researchers have created novel supplementary materials and delivery systems. The goal of this review article is to provide vaccine formulation researchers with the most up-to-date information on vaccine formulation and the immunological mechanisms available, to identify the technical challenges associated with the commercialization of non-invasive vaccines, and to guide future research and development efforts.
The lack of knowledge about the absorption, distribution, metabolism, and excretion (ADME) of vaccines makes biopharmaceutical optimization difficult. This was shown during the COVID-19 immunization campaign, where gradual booster doses were introduced as the initial dose was not offering broad protection against infection. Thus, understanding vaccine ADME and its effects on immunization effectiveness could result in a more logical vaccine design in terms of formulation, method of administration, and dosing regimens. Herein, we will cover the information available on vaccine pharmacokinetics, impacts of delivery routes and carriers on ADME, utilization and efficiency of nanoparticulate delivery vehicles, impact of dose level and dosing schedule on the therapeutic efficacy of vaccines, intracellular and endosomal trafficking and in vivo fate, perspective on DNA and mRNA vaccines, new generation sequencing and mathematical models to improve cancer vaccination and pharmacology, and the reported toxicological study of COVID-19 vaccines. Altogether, this review will enhance the reader's understanding of the pharmacokinetics of vaccines and methods that can be implied in delivery vehicle design to improve the absorption and distribution of immunizing agents and estimate the appropriate dose to achieve better immunogenic responses and prevent toxicities.
We report a multi-step approach for the synthesis of protein-imprinted polymeric particles that selectively bind tumor necrosis factor alpha (TNFα). With high affinity for TNF-α, this type of polymer may provide a novel, safe treatment or preventive approach for addressing inflammatory bowel diseases (e.g., Crohn's disease, ulcerative colitis).A key element in the approach is the use of functional monomers (FMs) based on the amino acid tyrosine, known to play a uniquely dominant role in antibody combining sites and providing high affinity for the protein. TNFα binding in the, not yet optimized, PIP particles were found to be 14 times that of the NIPs.In vitro experiments with TNFα imprinted polymers indicated no toxicity towards L929 and Caco-2 reporter cell lines and effective in reducing TNFα-induced cell death. The results corroborate the potential of such particles to treat, or prevent, inflammatory bowel diseases, currently treated with systemically delivered biologics. The results bode well for the general development of non-systemic, orally delivered and safe, imprinted polymeric drugs that can act in the gastrointestinal tract where antibodies cannot readily be used.
