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International Journal of Biological... Sep 2023This study aims to provide a thorough characterization of Brij O2-stabilized gliadin nanoparticles to be used for the potential oral administration of various compounds....
This study aims to provide a thorough characterization of Brij O2-stabilized gliadin nanoparticles to be used for the potential oral administration of various compounds. Different techniques were used in order to evaluate their physico-chemical features and then in vivo studies in rats were performed for the investigation of their biodistribution and gastrointestinal transit profiles. The results showed that the gliadin nanoparticles accumulated in the mucus layer of the bowel mucosa and evidenced their ability to move along the digestive systems of the animals. The incubation of the nanosystems with Caenorhabditis elegans, used as an additional in vivo model, confirmed the intake of the particles and evidenced their presence along the entire gastrointestinal tract of these nematodes. The gliadin nanoparticles influenced neither the egg-laying activity of the worms nor their metabolism of lipids up to 10 μg/mL of nanoformulation. The systems decreased the content of the age-related lipofuscin pigment in the nematodes in a dose-dependent manner, demonstrating a certain antioxidant activity. Lastly, dihydroethidium staining showed the absence of oxidative stress upon incubation of the worms together with the formulations, confirming their safe profile. This data paves the way for the future application of the proposed nanosystems regarding the oral delivery of various bioactives.
Topics: Rats; Animals; Gliadin; Tissue Distribution; Nanoparticles; Administration, Oral; Gastrointestinal Tract
PubMed: 37541472
DOI: 10.1016/j.ijbiomac.2023.126111 -
Journal of Controlled Release :... Nov 2023The formation of a biomolecular corona on exogenous particles in plasma is well studied and is known to dictate the biodistribution and cellular interactions of... (Review)
Review
The formation of a biomolecular corona on exogenous particles in plasma is well studied and is known to dictate the biodistribution and cellular interactions of nanomedicine formulations. In contrast, while the oral route is the most favorable administration method for pharmaceuticals, little is known about the formation and composition of the corona formed by biomolecules on particles within the gastrointestinal tract. This work reviews the current literature understanding of (1) the formation of drug particles after oral administration, (2) the formation of a biomolecular corona within the gastrointestinal tract ("the gastrointestinal corona"), and (3) the possible implications of the formation of a gastrointestinal corona on the interactions of drug particles with their biological environment. In doing so, this work aims to establish the significance of the formation of a gastrointestinal corona in oral drug delivery to ultimately arrive at new avenues to control the behavior of orally administered pharmaceuticals.
Topics: Tissue Distribution; Nanoparticles; Gastrointestinal Tract; Administration, Oral; Pharmaceutical Preparations
PubMed: 37776905
DOI: 10.1016/j.jconrel.2023.09.049 -
Chimia Jun 2021Peptides have a number of attractive properties that make them an interesting modality for drug development, including their ability to bind challenging targets, their... (Review)
Review
Peptides have a number of attractive properties that make them an interesting modality for drug development, including their ability to bind challenging targets, their high target specificity, and their non-toxic metabolic products. However, a major limitation of peptides as drugs is their typically poor oral availability, hindering their convenient and flexible application as pills. Of the more than 60 approved peptide drugs, the large majority is not orally applicable. The oral delivery of peptides is hampered by their metabolic instability and/or limited intestinal uptake. In this article, we review the barriers peptides need to overcome after their oral administration to reach disease targets, we highlight two recent successes of pharma companies in developing orally applicable peptide drugs, and we discuss efforts of our laboratory towards the generation of bioavailable cyclic peptides.
Topics: Administration, Oral; Drug Delivery Systems; Peptides; Peptides, Cyclic
PubMed: 34233815
DOI: 10.2533/chimia.2021.514 -
International Journal of Pharmaceutics Sep 2020How prevalent are peptide therapeutic products? How innovative are the formulations used to deliver peptides? This review provides a critical analysis of therapeutic... (Review)
Review
How prevalent are peptide therapeutic products? How innovative are the formulations used to deliver peptides? This review provides a critical analysis of therapeutic peptide products and the formulations approved by the United States Food and Drug administration (FDA), the European Medicines Agency (EMA), and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA). This review also provides an in-depth analysis of dosage forms and administration routes for delivering peptide therapeutics, including injectables, oral dosage forms, and other routes of administration. We discuss the function of excipients in parenteral formulations in detail, since most peptide therapeutics are parenterally administered. We provide case studies of alternate delivery routes and dosage forms. Based on our analysis, therapeutic peptides administered as injectables remain the most commonly used dosage forms, particularly in the form of subcutaneous, intravenous, or intramuscular injections. In addition, therapeutic peptides are formulated to achieve prolonged release, often through the use of polymer carriers. The limited number of oral therapeutic peptide products and their poor absorption and subsequent low bioavailability indicate a need for new technologies to broaden the formulation design space. Therapeutic peptide products may also be delivered through other administration routes, including intranasal, implant, and sublingual routes. Therefore, an in-depth understanding of how therapeutic peptides are now formulated and administered is essential to improve peptide delivery, improve patient compliance, and reduce the healthcare burden for these crucial therapeutic agents.
Topics: Administration, Intranasal; Administration, Oral; Drug Delivery Systems; Excipients; Humans; Peptides; United States
PubMed: 32622810
DOI: 10.1016/j.ijpharm.2020.119491 -
Frontiers in Immunology 2023In today's aging society, dementia is an urgent problem to be solved because no treatment or preventive methods have been established. This review focuses on oral... (Review)
Review
In today's aging society, dementia is an urgent problem to be solved because no treatment or preventive methods have been established. This review focuses on oral administration of lipopolysaccharide (LPS), an outer membrane component of Gram-negative bacteria, as a novel preventive drug for dementia. LPS is also called endotoxin and is well known to induce inflammation when administered systemically. On the other hand, although we humans routinely ingest LPS derived from symbiotic bacteria of edible plants, the effect of oral administration of LPS has hardly been studied. Recently, oral administration of LPS was reported to prevent dementia by inducing neuroprotective microglia. Furthermore, it has been suggested that colony stimulating factor 1 (CSF1) is involved in the dementia prevention mechanism by oral administration of LPS. Thus, in this review, we summarized the previous studies of oral administration of LPS and discussed the predicted dementia prevention mechanism. In addition, we showed the potential of oral LPS administration as a preventive drug for dementia by highlighting research gaps and future issues for clinical application development.
Topics: Humans; Lipopolysaccharides; Microglia; Endotoxins; Administration, Oral; Dementia
PubMed: 36969154
DOI: 10.3389/fimmu.2023.1110583 -
European Journal of Pharmaceutical... Sep 2022The infinite time of oral drug absorption was conceived from the first day of the birth of pharmacokinetics when H. Dost introduced the term pharmacokinetics in his book... (Review)
Review
The infinite time of oral drug absorption was conceived from the first day of the birth of pharmacokinetics when H. Dost introduced the term pharmacokinetics in his book published in 1953. He adopted the function developed by H. Bateman back in 1908 for the decay of the nuclei isotopes to describe oral drug absorption as a first-order process. We unveiled this false hypothesis relying on common wisdom i.e. drugs are absorbed in finite time. This false assumption had dramatic effects on the evolution of oral pharmacokinetics but most importantly on the bioavailability and bioequivalence concepts and metrics. This work focuses on the finite absorption time (FAT) concept, the relevant Physiologically Based Finite Time (PBFTPK) models developed and their applications in oral pharmacokinetics, bioavailability and bioequivalence. The crux of the matter is that drug absorption from the gastrointestinal tract takes place under sink conditions because of the high blood flow rate in the vena cava. The termination of oral, pulmonary and intranasal drug absorption at a specific time point, calls for regulatory changes in bioavailability and bioequivalence studies in terms of the study design and metrics used for the bioequivalence assessment.
Topics: Administration, Oral; Biological Availability; Gastrointestinal Tract; Humans; Male; Pharmacokinetics; Therapeutic Equivalency
PubMed: 35863551
DOI: 10.1016/j.ejps.2022.106265 -
Trends in Biotechnology Mar 2022Genetically engineered microbes that secrete therapeutics, sense and respond to external environments, and/or target specific sites in the gut fall under an emergent... (Review)
Review
Genetically engineered microbes that secrete therapeutics, sense and respond to external environments, and/or target specific sites in the gut fall under an emergent class of therapeutics, called live biotherapeutic products (LBPs). As live organisms that require symbiotic host interactions, LBPs offer unique therapeutic opportunities, but also face distinct challenges in the gut microenvironment. In this review, we describe recent approaches (often demonstrated using traditional probiotic microorganisms) to discover LBP chassis and genetic parts utilizing omics-based methods and highlight LBP delivery strategies, with a focus on addressing physiological challenges that LBPs encounter after oral administration. Finally, we share our perspective on the opportunity to apply an integrated approach, wherein discovery and delivery strategies are utilized synergistically, towards tailoring and optimizing LBP efficacy.
Topics: Administration, Oral; Genetic Engineering; Probiotics
PubMed: 34481657
DOI: 10.1016/j.tibtech.2021.08.002 -
The American Journal of Managed Care Feb 2013
Topics: Administration, Oral; Dietary Supplements; Humans; United States
PubMed: 23448108
DOI: No ID Found -
Journal of Nanobiotechnology Oct 2021Oral administration is an appealing route of delivering cancer treatments. However, the gastrointestinal tract is characterized by specific and efficient physical,... (Review)
Review
Oral administration is an appealing route of delivering cancer treatments. However, the gastrointestinal tract is characterized by specific and efficient physical, chemical, and biological barriers that decrease the bioavailability of medications, including chemotherapeutics. In recent decades, the fields of material science and nanomedicine have generated several delivery platforms with high potential for overcoming multiple barriers associated to oral administration. This review describes the properties of several nanodelivery systems that improve the bioavailability of orally administered therapeutics, highlighting their advantages and disadvantages in generating successful anticancer oral nanomedicines.
Topics: Administration, Oral; Animals; Antineoplastic Agents; Biological Availability; Drug Delivery Systems; Humans; Nanomedicine; Neoplasms; Pharmaceutical Preparations
PubMed: 34717658
DOI: 10.1186/s12951-021-01100-2 -
Chimia Jun 2021This review on intracellular delivery and oral bioavailability of peptides reflects a number of principal investigations at Novartis. Our studies were aimed at either... (Review)
Review
This review on intracellular delivery and oral bioavailability of peptides reflects a number of principal investigations at Novartis. Our studies were aimed at either understanding features enabling peptides to interfere with intracellular protein-protein interactions, or to achieve a more patient-friendly delivery by the oral route. In the light of these objectives, we have also spent some effort on assay development to come up with alternative methods for monitoring cellular peptide uptake. This summary of our insights is intended to help in the assessment and development of peptide therapeutics requiring membrane transition.
Topics: Administration, Oral; Biological Availability; Biological Transport; Humans; Peptides; Permeability
PubMed: 34233817
DOI: 10.2533/chimia.2021.522