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Drug Discovery Today Aug 2022Oral delivery is preferred over other routes of drug administration by both patients and physicians. The bioavailability of some therapeutics that are delivered via the... (Review)
Review
Oral delivery is preferred over other routes of drug administration by both patients and physicians. The bioavailability of some therapeutics that are delivered via the oral route is restricted due to the protease- and bacteria-rich environment in the gastrointestinal tract, and by the pH variability along the delivery route. Given these harsh environments, the oral delivery of therapeutic macromolecules is complicated and remains challenging. Various formulation approaches, including the use of permeation enhancers and nanosized carriers, as well as chemical alteration of the drug structure, have been studied as ways to improve the oral absorption of macromolecular drugs. Nevertheless, the bioavailability of marketed oral peptide medicines is often relatively poor. This review highlights the most recent and promising physical methods for improving the oral bioavailability of macromolecules such as peptides. These methods include microneedle injections, high-speed stream injectors, magnetic drug targeting, expandable hydrogels, and iontophoresis. We highlight the potential and challenges of these new technologies, which may impact the future approaches used by pharmaceutical companies to create more efficient and safer orally administered macromolecules.
Topics: Administration, Oral; Biological Availability; Drug Delivery Systems; Gastrointestinal Tract; Humans; Hydrogels; Macromolecular Substances; Peptides
PubMed: 35460891
DOI: 10.1016/j.drudis.2022.04.014 -
Pharmacological Research Nov 2023Echinacoside, a natural phenylethanoid glycoside, was discovered and isolated from the garden plant Echinacea angustifolia DC., belonging to the Compositae family,... (Review)
Review
Echinacoside, a natural phenylethanoid glycoside, was discovered and isolated from the garden plant Echinacea angustifolia DC., belonging to the Compositae family, approximately sixty years ago. Extensive investigations have revealed that it possesses a wide array of pharmacologically beneficial activities for human health, particularly notable for its neuroprotective and anticancer activity. Several crucial concerns surfaced, encompassing the recognition of active metabolites that exhibited inadequate bioavailability in their prototype form, the establishment of precise molecular signal pathways or targets associated with the aforementioned effects of echinacoside, and the scarcity of dependable clinical trials. Hence, the question remains unanswered as to whether scientific research can effectively utilize this natural compound. To support future studies on this natural product, it is imperative to provide a systematic overview and insights into potential future prospects. The current review provides a comprehensive analysis of the existing knowledge on echinacoside, encompassing its wide distribution, structural diversity and metabolism, diverse therapeutic applications, and improvement of echinacoside bioavailability for its potential utilization.
Topics: Humans; Glycosides; Asteraceae; Biological Availability; Biological Products
PubMed: 37804927
DOI: 10.1016/j.phrs.2023.106951 -
International Journal of Molecular... Oct 2023Nano-range bioactive colloidal carrier systems are envisaged to overcome the challenges associated with treatments of numerous diseases. Lipid nanoparticles (LNPs), one... (Review)
Review
Nano-range bioactive colloidal carrier systems are envisaged to overcome the challenges associated with treatments of numerous diseases. Lipid nanoparticles (LNPs), one of the extensively investigated drug delivery systems, not only improve pharmacokinetic parameters, transportation, and chemical stability of encapsulated compounds but also provide efficient targeting and reduce the risk of toxicity. Over the last decades, nature-derived polyphenols, vitamins, antioxidants, dietary supplements, and herbs have received more attention due to their remarkable biological and pharmacological health and medical benefits. However, their poor aqueous solubility, compromised stability, insufficient absorption, and accelerated elimination impede research in the nutraceutical sector. Owing to the possibilities offered by various LNPs, their ability to accommodate both hydrophilic and hydrophobic molecules and the availability of various preparation methods suitable for sensitive molecules, loading natural fragile molecules into LNPs offers a promising solution. The primary objective of this work is to explore the synergy between nature and nanotechnology, encompassing a wide range of research aimed at encapsulating natural therapeutic molecules within LNPs.
Topics: Biological Availability; Dietary Supplements; Liposomes; Drug Delivery Systems; Nanoparticles
PubMed: 37958750
DOI: 10.3390/ijms242115764 -
Journal of Biological Inorganic... Jun 2020The association of proteins with metals, metalation, is challenging because the tightest binding metals are rarely the correct ones. Inside cells, correct metalation is... (Review)
Review
The association of proteins with metals, metalation, is challenging because the tightest binding metals are rarely the correct ones. Inside cells, correct metalation is enabled by controlled bioavailability plus extra mechanisms for tricky combinations such as iron and manganese.
Topics: Biological Availability; Chemistry, Bioinorganic; Humans; Metals, Heavy; Proteins
PubMed: 32333210
DOI: 10.1007/s00775-020-01790-3 -
Molecules (Basel, Switzerland) Sep 2021Nutraceuticals possess several health benefits and functions; however, most nutraceuticals are prone to degradation in the gastrointestinal environment and have poor... (Review)
Review
Nutraceuticals possess several health benefits and functions; however, most nutraceuticals are prone to degradation in the gastrointestinal environment and have poor bioavailability. Application of a novel carrier system is of increasing importance to overcome obstacles and provide efficient applicability. Lipid-based nanocarriers provide a large surface-to-mass ratio, enhanced intestinal absorption by solubilization in the intestinal milieu, intestinal lymphatic transport, and altering enterocyte-based transport. A critical overview of the current limitation, preparation, and application of lipid-based nanocarriers (liposomes and niosomes) and lipid nanoparticles (SLNs and NLCs) is discussed. Physical and gastrointestinal stability and bioavailability of nanoencapsulated nutraceuticals are considered as well.
Topics: Administration, Oral; Biological Availability; Dietary Supplements; Drug Carriers; Humans; Lipids; Nanoparticles
PubMed: 34576981
DOI: 10.3390/molecules26185510 -
Scientific Reports Oct 2020Calcium is an important mineral that plays an integral role in human health, especially bone health. Marine biological calcium is an abundant resource that is generally... (Review)
Review
Calcium is an important mineral that plays an integral role in human health, especially bone health. Marine biological calcium is an abundant resource that is generally accepted and has a complex active structure. This review evaluates research progress on marine biological calcium with regards to its sources, use of calcium supplements, calcium bioavailability, and novel applications of marine calcium. The potential for future development and the use of products incorporating marine biological calcium in biomedical research and the pharmaceutical, health care, and food industries are also reviewed. The goal of this review is to provide a comprehensive documentation on resource utilization and product development from marine organisms.
Topics: Animals; Aquatic Organisms; Biological Availability; Calcium; Dietary Supplements
PubMed: 33116162
DOI: 10.1038/s41598-020-75575-8 -
Drug Delivery Dec 2022Self-emulsifying drug delivery systems (SEDDS) are a proven method for poorly soluble substances works by increasing the solubility and bioavailability. SEDDS and... (Review)
Review
Self-emulsifying drug delivery systems (SEDDS) are a proven method for poorly soluble substances works by increasing the solubility and bioavailability. SEDDS and isotropic mixtures, are composed of oils, surfactants, and occasionally cosolvents. The ability of these formulations and methods to produce microemulsions or fine oil-in-water (o/w) emulsions after moderate stirring and dilution by water phase along the GI tract might be a promising technique for lipophilic agents with dissolution rate-limited absorption. This review provides an outline of SEDDS's numerous advances and biopharmaceutical elements, types, manufacturing, characterization, limitations, and future prospects. The evaluation of SEDDS and its applications are also discussed, focusing on the advances of SEDDS's solid self-emulsifying delivery mechanism and dosage form. By integrating suitable polymer into the formulation, SEDDS may be studied for the creation of a formulation with sustained drug release. This technology's improvement might lead to a new application in the field of medicine delivery. SEDDS has been demonstrated to be quite efficient in increasing oral bioavailability of lipophilic products. SEDDS is one of the promising methods for controlling the characteristics of medications that are not great choices for oral delivery. It is also worth mentioning that SEDDS may be made in variety of solid dosage forms that are acceptable for both oral and parenteral administration.
Topics: Administration, Oral; Biological Availability; Drug Delivery Systems; Emulsions; Solubility; Water
PubMed: 35666090
DOI: 10.1080/10717544.2022.2083724 -
Journal of Nanobiotechnology Dec 2022Norcantharidin (NCTD) is a demethylated derivative of cantharidin (CTD), the main anticancer active ingredient isolated from traditional Chinese medicine Mylabris. NCTD... (Review)
Review
Norcantharidin (NCTD) is a demethylated derivative of cantharidin (CTD), the main anticancer active ingredient isolated from traditional Chinese medicine Mylabris. NCTD has been approved by the State Food and Drug Administration for the treatment of various solid tumors, especially liver cancer. Although NCTD greatly reduces the toxicity of CTD, there is still a certain degree of urinary toxicity and organ toxicity, and the poor solubility, short half-life, fast metabolism, as well as high venous irritation and weak tumor targeting ability limit its widespread application in the clinic. To reduce its toxicity and improve its efficacy, design of targeted drug delivery systems based on biomaterials and nanomaterials is one of the most feasible strategies. Therefore, this review focused on the studies of targeted drug delivery systems combined with NCTD in recent years, including passive and active targeted drug delivery systems, and physicochemical targeted drug delivery systems for improving drug bioavailability and enhancing its efficacy, as well as increasing drug targeting ability and reducing its adverse effects.
Topics: United States; Bridged Bicyclo Compounds, Heterocyclic; Drug Delivery Systems; Half-Life; Biological Availability; Neoplasms
PubMed: 36463199
DOI: 10.1186/s12951-022-01703-3 -
Colloids and Surfaces. B, Biointerfaces Sep 2022Biotherapeutic development presents a myriad of challenges in relation to delivery, in particular for protein therapeutics. Protein delivery is complicated due to...
Biotherapeutic development presents a myriad of challenges in relation to delivery, in particular for protein therapeutics. Protein delivery is complicated due to hydrophilicity, size, rate of degradation in vivo, low permeation through biological barriers, pH and temperature sensitivity, as well as the need to conserve its quaternary structure to retain function. To preserve therapeutic levels in vivo, proteins require frequent administration due to their short half-lives. Formulation strategies combining proteins with lipid carriers for parenteral administration show potential for improving bioavailability, while preserving protein activity and bypassing the mucosal barriers of the body. Encapsulating protein in long acting injectable delivery systems can improve therapeutic indices by prolonging and controlling protein release and reducing the need for repeat interventions. Two lyotropic crystal forming lipids, monoolein and phytantriol, have been formulated to produce lipidic cubic phases and assessed for their use as long acting protein eluting injectables. Three soluble proteins, cytochrome c, glyceraldehyde-3-phosphate dehydrogenase and aldehyde dehydrogenase and one membrane protein, cytochrome c oxidase, were incorporated into bulk cubic phase formulations of each lipid system to comparatively assess protein release kinetics. The activity of the soluble proteins was measured upon release from a phytantriol bulk cubic phase and phytantriol cubosomes, produced using a liquid precursor method.
Topics: Biological Availability; Liquid Crystals
PubMed: 35816882
DOI: 10.1016/j.colsurfb.2022.112644 -
International Journal of Nanomedicine 2022Bioavailability is an eternal topic that cannot be circumvented by peroral drug delivery. Adequate blood drug exposure after oral administration is a prerequisite for... (Review)
Review
Bioavailability is an eternal topic that cannot be circumvented by peroral drug delivery. Adequate blood drug exposure after oral administration is a prerequisite for effective treatment. Nanovesicles as pleiotropic oral vehicles can solubilize, encapsulate, stabilize an active ingredient and promote the payload absorption via various mechanisms. Vesicular systems with nanoscale size, such as liposomes, niosomes and polymersomes, provide a versatile platform for oral delivery of drugs with distinct nature. The amphiphilicity of vesicles in structure allows hydrophilic and lipophilic molecule(s) either or both to be loaded, being encapsulated in the aqueous cavity or the inner core, respectively. Depending on high oral transport efficiency based on their structural flexibility, gastrointestinal stability, biocompatibility, and/or intestinal epithelial affinity, nanovesicles can markedly augment the oral bioavailability of various poorly absorbed drugs. Vesicular drug delivery systems (VDDSs) demonstrate a lot of preferences and are becoming more prominent of late years in biomedical applications. Equally, these systems can potentiate a drug's therapeutic index by ameliorating the oral absorption. This review devotes to comment on various VDDSs with special emphasis on the peroral drug delivery. The classification of nanovesicles, preparative processes, intestinal transport mechanisms, in vivo fate, and design rationale were expounded. Knowledge on vesicles-mediated oral drug delivery for bioavailability enhancement has been properly provided. It can be concluded that VDDSs with many merits will step into an energetic arena in oral drug delivery.
Topics: Biological Availability; Liposomes; Administration, Oral; Hydrophobic and Hydrophilic Interactions; Excipients
PubMed: 36262189
DOI: 10.2147/IJN.S382192