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Journal of Controlled Release :... Aug 2022Targeting the release of drugs in specific sites of the upper GI tract would meet local therapeutic goals, improve the bioavailability of specific drugs and help... (Review)
Review
Targeting the release of drugs in specific sites of the upper GI tract would meet local therapeutic goals, improve the bioavailability of specific drugs and help overcoming compliance-related limitations, especially in chronic illnesses of great social/economic impact and involving polytherapies (e.g. Parkinson's and Alzeimer's disease, tubercolosis, malaria, HIV, HCV). It has been traditionally pursued using gastroretentive (GR) systems, i.e. low-density, high-density, magnetic, adhesive and expandable devices. More recently, the interest towards oral administration of biologics has prompted the development of novel drug delivery systems (DDSs) provided with needles and able to inject different formulations in the mucosa of the upper GI tract and particularly of esophagus, stomach or small intestine. Besides comprehensive literature analysis, DDSs identified as smart devices in view of their high degree of complexity in terms of design, working mechanism, materials employed and manufacturing steps were discussed making use of graphic tools.
Topics: Administration, Oral; Biological Availability; Drug Compounding; Drug Delivery Systems; Drug Liberation; Upper Gastrointestinal Tract
PubMed: 35690278
DOI: 10.1016/j.jconrel.2022.06.005 -
STAR Protocols Mar 2021Substances are commonly administered orally in mouse experiments. Here, I describe how to voluntarily administer substances orally in a time- and dose-controlled manner...
Substances are commonly administered orally in mouse experiments. Here, I describe how to voluntarily administer substances orally in a time- and dose-controlled manner to laboratory mice. This minimizes injury potential and stress often associated with the commonly used intragastric gavage technique. Here, the drug is incorporated into artificially sweetened and flavored jelly and given to mice previously trained to eat the jelly. This can be used for acute and chronic oral drug treatment or for oral glucose tolerance tests. For complete details on the use and execution of this protocol, please refer to Zhang et al. (2010) and Cox et al. (2010).
Topics: Administration, Oral; Animal Feed; Animals; Drug Evaluation, Preclinical; Mice; Sweetening Agents
PubMed: 33644770
DOI: 10.1016/j.xpro.2021.100330 -
Archives of Razi Institute Oct 2022In some developing countries in Africa, Asia, and Latin America, rapid population growth is a complicated problem, and thus, it is necessary to raise the efficiency of...
In some developing countries in Africa, Asia, and Latin America, rapid population growth is a complicated problem, and thus, it is necessary to raise the efficiency of foodstuff production to preserve human life. Therefore, this study was designed to investigate the effect of fish oil supplementation on male rabbits' productivity, as well as their biochemical and physiological characteristics. This experiment was conducted in the Animal House of the College of Veterinary Medicine, University of Baghdad (Baghdad, Iraq) for eight weeks. Twenty-four local male rabbits were randomly divided into three groups (each containing eight rabbits) as follows: the control group that was fed with a basal diet only, the first treated group in which each animal received fish oil orally at a dose of 0.75 ml every day, and another treated group in which each animal received fish oil orally at a dose of 1.5 ml every day. Both treated groups received the treatment for 60 days. Blood samples were collected from cardiac veins by cardiac puncture at the beginning of the experiment (Zero time). On day 60 of the experiment, samples were collected again to analyze potential changes in blood characteristics, including white blood cells count, hemoglobin, and red blood cells count. These blood samples recorded a significant decrease in cholesterol in the two treatment groups, compared to the control. In conclusion, the current findings recommend daily oral administration of fish oil at a dose of 0.75 mg/ml or 1.5 mg/ml to rabbits for 60 days before conception to improve performance trials, as well as biochemical and hematological results. These alterations, however, have a small impact on these features, compared to higher doses administered to rabbits.
Topics: Animals; Male; Rabbits; Administration, Oral; Cholesterol; Diet; Fish Oils; Iraq
PubMed: 37123147
DOI: 10.22092/ARI.2022.357977.2123 -
Yakugaku Zasshi : Journal of the... 2015Drug products are developed to meet multiple targets, thereby increasing their value. Pharmaceutical scientists encounter several trade-offs during the development of... (Review)
Review
Drug products are developed to meet multiple targets, thereby increasing their value. Pharmaceutical scientists encounter several trade-offs during the development of novel oral formulations. These trade-offs are generated by their desire to supply the highest possible quality products under the prevailing conditions of limited time and cost, and feasible options. When there are two incompatible factors, it is sometimes difficult to dismiss one element. This is because a quality target product profile (QTPP) is critical for each product being developed, and all elements should basically be satisfied with the criteria. Therefore, technological innovation becomes important to overcome the trade-offs. This article introduces examples of such innovations which have been successful in doing this, as well as some encountered in the oral formulation development and in the selection of proper dosage forms. Based on these examples, points to be considered in order to produce the drug product are thoroughly discussed.
Topics: Administration, Oral; Dosage Forms; Drug Design; Humans; Solubility
PubMed: 25747218
DOI: 10.1248/yakushi.14-00228-2 -
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 -
Anaesthesia Oct 2016
Topics: Acetaminophen; Administration, Intravenous; Administration, Oral; Analgesics, Non-Narcotic; Critical Care; Humans
PubMed: 27611037
DOI: 10.1111/anae.13517 -
The Journal of Toxicological Sciences 2022Although both o-toluidine and o-anisidine are known as aromatic amines with bladder carcinogenicity, the specific metabolites involved in carcinogenesis are still...
Although both o-toluidine and o-anisidine are known as aromatic amines with bladder carcinogenicity, the specific metabolites involved in carcinogenesis are still unclear. Here, we examined the toxicological effects of head-to-tail dimers of o-toluidine and o-anisidine, 2-methyl-N-(2-methylphenyl) benzene-1,4-diamine (MMBD) and 2-methoxy-N-(2-methoxyphenyl) benzene-1,4-diamine (MxMxBD), respectively, in rats. Six-week-old male F344 rats were orally administered MMBD, MxMxBD, o-toluidine, and o-anisidine at a dose of 100 mg/kg/day for 28 days. Rats administered 400 mg/kg o-toluidine and 600 mg/kg/day o-anisidine were set as high-dose groups for comparison. Histopathology and immunohistochemistry for γ-H2AX, a DNA damage biomarker, and bladder stem cell markers, including aldehyde dehydrogenase 1A1 (ALDH1A1), were performed. MMBD and MxMxBD caused different toxicities than their monomers, inducing hepatotoxicity such as vacuolar degeneration but not splenic lesions due to methemoglobinemia. Bladder lesions, including urothelial hyperplasia, were observed in the high-dose o-toluidine and o-anisidine groups, whereas no obvious changes were induced in the low-dose groups or their dimers. Although γ-H2AX formation was significantly increased by o-toluidine and o-anisidine treatment, γ-H2AX formation did not differ among the MMBD, MxMxBD, and control groups. Notably, immunohistochemistry revealed marked increases in ALDH1A1 expression in the bladder urothelium of the MMBD and MxMxBD groups and in the o-toluidine and o-anisidine groups, suggesting that the two dimers may contribute to the bladder carcinogenic effects of o-toluidine and o-anisidine to some extent. The degrees of bladder lesions and γ-H2AX formation did not correlate with the amount of unchanged o-toluidine and o-anisidine in urine, indicating the presence of other metabolites responsible for these findings.
Topics: Rats; Male; Animals; Rats, Inbred F344; Benzene; Administration, Oral; Diamines
PubMed: 36328536
DOI: 10.2131/jts.47.457 -
British Medical Journal Feb 1979
Topics: Administration, Oral; Biological Availability; Food; Humans; Intestinal Absorption; Liver Circulation
PubMed: 421083
DOI: No ID Found -
The Journal of Thoracic and... Nov 2020
Topics: Administration, Oral; Anticoagulants; Cardiac Surgical Procedures; Risk Factors; Smoke
PubMed: 31711620
DOI: 10.1016/j.jtcvs.2019.09.094 -
European Journal of Pharmaceutics and... Oct 2023The establishment of latent cellular and anatomical viral reservoirs is a major obstacle to achieving a cure for people infected by HIV. Mesenteric lymph nodes (MLNs)...
The establishment of latent cellular and anatomical viral reservoirs is a major obstacle to achieving a cure for people infected by HIV. Mesenteric lymph nodes (MLNs) are one of the most important anatomical reservoirs of HIV. Suboptimal levels of antiretroviral (ARVs) drugs in these difficult-to-penetrate viral reservoirs is one of the limitations of current antiretroviral therapy (ART) regimens. This study aimed to design and assess highly lipophilic ester prodrugs of dolutegravir (DTG) formulated with long-chain triglyceride (LCT) for delivery of DTG to the viral reservoir in mesenteric lymph and MLNs. A number of alkyl ester prodrugs of DTG were designed based on the predicted affinity to chylomicrons (CM), and the six most promising prodrugs were selected and synthesised. The synthesised prodrugs were further assessed for their intestinal lymphatic transport potential and biotransformation in biorelevant media in vitro and ex vivo. DTG and the most promising prodrug (prodrug 5) were then assessed in pharmacokinetic and biodistribution studies in rats. Although oral administration of 5 mg/kg of unmodified DTG (an allometrically scaled dose from humans) with or without lipids achieved concentrations above protein binding-adjusted IC (PA-IC) (64 ng/mL) in most tissues, the drug was not selectively targeted to MLNs. The combination of lipophilic ester prodrug and LCT-based formulation approach improved the targeting selectivity of DTG to MLNs 4.8-fold compared to unmodified DTG. However, systemic exposure to DTG was limited, most likely due to poor intestinal absorption of the prodrug following oral administration. In vitro lipolysis showed a good correlation between micellar solubilisation of the prodrug and systemic exposure to DTG in rats in vivo. Thus, it is prudent to include in vitro lipolysis in the early assessment of orally administered drugs and prodrugs in lipidic formulations, even when intestinal lymphatic transport is involved in the absorption pathway. Further studies are needed to clarify the underlying mechanisms of low systemic bioavailability of DTG following oral administration of the prodrug and potential ways to overcome this limitation.
Topics: Humans; Rats; Animals; Prodrugs; Esters; Tissue Distribution; Intestines; Triglycerides; Administration, Oral
PubMed: 37634824
DOI: 10.1016/j.ejpb.2023.08.015