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The Journal of Clinical Endocrinology... Apr 2021This mini-review provides an overview of menopausal hormone therapy (HT) and cardiovascular disease (CVD) risk, with a focus on the role of hormone formulation, dose,... (Review)
Review
CONTEXT
This mini-review provides an overview of menopausal hormone therapy (HT) and cardiovascular disease (CVD) risk, with a focus on the role of hormone formulation, dose, and route of delivery.
METHODS
This summary is based on authors' knowledge in the field of menopausal HT and supplemented by a PubMed search using the terms "menopause hormone therapy," "transdermal," "estradiol," "conjugated estrogens," "bioidentical," "cardiovascular disease," "lipoproteins," "glucose," "progestogens," "low dose."
RESULTS
Available evidence indicates that oral unopposed estrogens have a favorable effect on lipoprotein levels, glycemia, insulin, and CVD risk; however, the addition of progestogens blunts the lipid-related effects. The progestogen with the smallest attenuating effect is micronized progesterone. Transdermal estrogens have less effect on coagulation, inflammation, and lipids than oral estrogens and observational studies suggest they pose a lower risk of venous thromboembolism and stroke than oral estrogens. Clinical effects of hormones were not consistently dose dependent.
CONCLUSIONS
Although HT continues to have an important role in menopause management, it is not recommended for primary or secondary CVD prevention. Different formulations, doses, and routes of delivery of HT have different effects on cardiometabolic markers and risks of clinical CVD events. However, long-term trials evaluating clinical outcomes with transdermal and other alternate HT regimens are limited.
Topics: Administration, Cutaneous; Cardiovascular Diseases; Dose-Response Relationship, Drug; Drug Administration Routes; Drug Compounding; Estradiol; Estrogen Replacement Therapy; Female; Humans; Menopause; Risk Factors
PubMed: 33506261
DOI: 10.1210/clinem/dgab042 -
International Journal of Toxicology 2016Formulation of nonclinical evaluations is a challenge, with the fundamental need to achieve multiples of the clinical exposure complicated by differences in species and... (Review)
Review
Formulation of nonclinical evaluations is a challenge, with the fundamental need to achieve multiples of the clinical exposure complicated by differences in species and routes of administration-specific tolerances, depending on concentrations, volumes, dosing regimen, duration of each administration, and study duration. Current practice to approach these differences is based on individual experience and scattered literature with no comprehensive data source (the most notable exception being our 2006 publication on this same subject). Lack of formulation tolerance data results in excessive animal use, unplanned delays in the evaluation and development of drugs, and vehicle-dependent results. A consulting firm, a chemical company, and 4 contract research organizations conducted a rigorous data mining operation of vehicle data from studies dating from 1991 to 2015, enhancing the data from this author's 2006 publication (3 of the six 2015 contributors were also 2006 contributors). Additional data were found in the published literature. The results identified 108 single-component vehicles (and 305 combination formulations) used in more than 1,040 studies across multiple species (dog, primate, rat, mouse, rabbit, guinea pig, minipig, pig, chick embryo, and cat) by multiple routes for a wide range of study durations. The tabulated data include maximum tolerated use levels by species, route, duration of study, dose-limiting toxicity where reported, review of the available literature on each vehicle, guidance on syringe selection, volume and pH limits by route with basic guidance on nonclinical formulation development, and guidance on factors to be considered in nonclinical route selection.
Topics: Animals; Dose-Response Relationship, Drug; Drug Administration Routes; Species Specificity; Toxicity Tests
PubMed: 26755718
DOI: 10.1177/1091581815622442 -
International Journal of Biological... May 2020Hyaluronic acid (HA) is a large non-sulphated glycosaminoglycan that is an important component of extracellular matrix (ECM) and a biodegradable polymer. Due to a... (Review)
Review
Hyaluronic acid: A review on its biology, aspects of drug delivery, route of administrations and a special emphasis on its approved marketed products and recent clinical studies.
Hyaluronic acid (HA) is a large non-sulphated glycosaminoglycan that is an important component of extracellular matrix (ECM) and a biodegradable polymer. Due to a variation in its molecular weight, HA derivatives can be utilized to make different formulations like fillers, creams, gels and drops. HA based drug research has seen a recent surge largely due to some properties like mucoadhesion, biocompatibility and ease of chemical modification. Such properties of HA have led to applications in tissue regeneration, anti-aging and anti-inflammatory medications. HA can be conjugated, functionalized or used as a nanocarrier supplement with a definite increase in its cellular uptake and efficiency. HA when encapsulated in a nanocarrier may help to improve the ECM growth and provide a sustained release of agents. This review discusses the mechanistic behavior of HA pertaining to its biological synthesis and degradation. It also discusses the administration of some noteworthy and recent HA based formulations through different routes for application in various physiological conditions along with their ongoing clinical trial updates and approved marketed products.
Topics: Clinical Studies as Topic; Drug Administration Routes; Drug Carriers; Drug Delivery Systems; Guided Tissue Regeneration; Humans; Hyaluronic Acid; Mechanical Phenomena; Molecular Structure
PubMed: 31715233
DOI: 10.1016/j.ijbiomac.2019.11.066 -
BMC Pregnancy and Childbirth Jan 2019Oxytocin for postpartum hemorrhage (PPH) prophylaxis is commonly administered by either intramuscular (IM) injection or intravenous (IV) infusion with both routes... (Randomized Controlled Trial)
Randomized Controlled Trial
Intramuscular injection, intravenous infusion, and intravenous bolus of oxytocin in the third stage of labor for prevention of postpartum hemorrhage: a three-arm randomized control trial.
BACKGROUND
Oxytocin for postpartum hemorrhage (PPH) prophylaxis is commonly administered by either intramuscular (IM) injection or intravenous (IV) infusion with both routes recommended equally and little discussion of potential differences between the two. This trial assesses the effectiveness and safety of 10 IU oxytocin administered as IM injection versus IV infusion and IV bolus during the third stage of labor for PPH prophylaxis.
METHODS
In two tertiary level Egyptian maternity hospitals, women delivering vaginally without exposure to pre-delivery uterotonics were randomized to one of three prophylactic oxytocin administration groups after delivery of the baby. Blood loss was measured 1 h after delivery, and side effects were recorded. Primary outcomes were mean postpartum blood loss and proportion of women with postpartum blood loss ≥500 ml in this open-label, three-arm, parallel, randomized controlled trial.
RESULTS
Four thousand nine hundred thirteen eligible, consenting women were randomized. Compared to IM injection, mean blood loss was 5.9% less in the IV infusion arm (95% CI: -8.5, - 3.3) and 11.1% less in the IV bolus arm (95% CI: -14.7, - 7.8). Risk of postpartum blood loss ≥500 ml in the IV infusion arm was significantly less compared to IM injection (0.8% vs. 1.5%, RR = 0.50, 95% CI: 0.27, 0.91). No side effects were reported in any arm.
CONCLUSIONS
Intravenous oxytocin is more effective than intramuscular injection for the prevention of PPH in the third stage of labor. Oxytocin delivered by IV bolus presents no safety concerns after vaginal delivery and should be considered a safe option for PPH prophylaxis.
TRIAL REGISTRATION
clinicaltrials.gov # NCT01914419 , posted August 2, 2013.
Topics: Administration, Intravenous; Adult; Delivery, Obstetric; Egypt; Female; Humans; Infusions, Intravenous; Injections, Intramuscular; Labor Stage, Third; Oxytocics; Oxytocin; Postpartum Hemorrhage; Pregnancy; Treatment Outcome
PubMed: 30658605
DOI: 10.1186/s12884-019-2181-2 -
Developments in Ophthalmology 2016The Endophthalmitis Vitrectomy Study (EVS) provided ophthalmologists with evidence-based management strategies to deal with endophthalmitis for the first time. However,... (Review)
Review
The Endophthalmitis Vitrectomy Study (EVS) provided ophthalmologists with evidence-based management strategies to deal with endophthalmitis for the first time. However, since the completion of the EVS, numerous unresolved issues remain. The use of oral antibiotics has important implications for the ophthalmologist, particularly in the prophylaxis and/or management of postoperative, posttraumatic, or bleb-associated bacterial endophthalmitis. One can reasonably conclude that significant intraocular penetration of an antibiotic after oral administration may be a property unique to the newer-generation fluoroquinolones. Prophylactic use of mupirocin nasal ointment resulted in significant reduction of conjunctival flora with or without preoperative topical 5% povidone-iodine preparation. Ocular fungal infections have traditionally been very difficult to treat due to limited therapeutic options both systemically and intravitreally. Because of its broad spectrum of coverage, low MIC90 levels for the organisms of concern, good tolerability, and excellent bioavailability, voriconazole through various routes of administration may be useful to the ophthalmologist in the primary treatment of or as an adjunct to the current management of ocular fungal infections.
Topics: Administration, Oral; Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacteria; Biological Availability; Drug Administration Routes; Drug Therapy, Combination; Endophthalmitis; Eye Infections, Bacterial; Humans; Microbial Sensitivity Tests
PubMed: 26501865
DOI: 10.1159/000438961 -
Drug Discovery Today Dec 2022Biotechnology-based therapeutics include a wide range of products, such as recombinant hormones, stem cells, therapeutic enzymes, monoclonal antibodies, genes, vaccines,... (Review)
Review
Biotechnology-based therapeutics include a wide range of products, such as recombinant hormones, stem cells, therapeutic enzymes, monoclonal antibodies, genes, vaccines, among others. The administration of these macromolecules has been studied via various routes. The nasal route is one of the promising routes of administration for biotechnology products owing to its easy delivery, the rich vascularity of the nasal mucosa, high absorption and targeted action. Several preclinical studies have been reported for nasal delivery of these products and many are at the clinical stage. This review focuses on biotechnology-based therapeutics administered via the intranasal route for treating various diseases.
Topics: Drug Delivery Systems; Administration, Intranasal; Nasal Mucosa; Vaccines; Biotechnology
PubMed: 36174965
DOI: 10.1016/j.drudis.2022.103371 -
International Journal of Pharmaceutics Dec 2019Mucosal administration, and specifically nasal route, constitutes an alternative and promising strategy for drug and vaccine delivery. Mucosal routes have several... (Review)
Review
Mucosal administration, and specifically nasal route, constitutes an alternative and promising strategy for drug and vaccine delivery. Mucosal routes have several advantages supporting their selective use for different pathologies. Currently, many efforts are being made to develop effective drug formulations and novel devices for nasal delivery. This review described the structure and main characteristics of the nasal cavity. The advantages, achievements and challenges of the nasal route use for medical purposes are discussed, with particular focus on vaccine delivery. Compelling evidences support the potentialities and safety of the nasal delivery of vaccines and drugs. This alternative route could become a solution for many unmet medical issues and also may facilitate and cheapen massive immunization campaigns or long-lasting chronic treatments. Nowadays, in spite of certain remaining skepticism, the field of nasal delivery of drugs and vaccines is growing fast, bolstered by current developments in nanotechnology, imaging and administration devices. A notable increase in the number of approved drugs for nasal administration is envisaged.
Topics: Administration, Intranasal; Animals; Drug Delivery Systems; Humans; Immunization; Nanotechnology; Nasal Cavity; Nasal Mucosa; Pharmaceutical Preparations; Vaccines
PubMed: 31678521
DOI: 10.1016/j.ijpharm.2019.118813 -
Advanced Drug Delivery Reviews Apr 2021Intercellular tight junctions represent a formidable barrier against paracellular drug absorption at epithelia (e.g., nasal, intestinal) and the endothelium (e.g.,... (Review)
Review
Intercellular tight junctions represent a formidable barrier against paracellular drug absorption at epithelia (e.g., nasal, intestinal) and the endothelium (e.g., blood-brain barrier). In order to enhance paracellular transport of drugs and increase their bioavailability and organ deposition, active excipients modulating tight junctions have been applied. First-generation of permeation enhancers (PEs) acted by unspecific interactions, while recently developed PEs address specific physiological mechanisms. Such target specific tight junction modulators (TJMs) have the advantage of a defined specific mechanism of action. To date, merely a few of these novel active excipients has entered into clinical trials, as their lack in safety and efficiency in vivo often impedes their commercialisation. A stronger focus on the development of such active excipients would result in an economic and therapeutic improvement of current and future drugs.
Topics: Animals; Drug Administration Routes; Drug Delivery Systems; Humans; Tight Junctions
PubMed: 33617902
DOI: 10.1016/j.addr.2021.02.008 -
Nature Reviews. Drug Discovery Jan 2019Biologics now constitute a significant element of available medical treatments. Owing to their clinical and commercial success, biologics are a rapidly growing class and... (Review)
Review
Biologics now constitute a significant element of available medical treatments. Owing to their clinical and commercial success, biologics are a rapidly growing class and have become a dominant therapeutic modality. Although most of the successful biologics to date are drugs that bear a peptidic backbone, ranging from small peptides to monoclonal antibodies (~500 residues; 150 kDa), new biologic modalities, such as nucleotide-based therapeutics and viral gene therapies, are rapidly maturing towards widespread clinical use. Given the rise of peptides and proteins in the pharmaceutical landscape, tremendous research and development interest exists in developing less-invasive or non-invasive routes for the systemic delivery of biologics, including subcutaneous, transdermal, oral, inhalation, nasal and buccal routes. This Review summarizes the current status, latest updates and future prospects for such delivery of peptides, proteins and other biologics.
Topics: Administration, Inhalation; Administration, Intranasal; Administration, Oral; Biological Products; Drug Administration Routes; Drug Carriers; Drug Delivery Systems; Drug Stability; Humans
PubMed: 30498202
DOI: 10.1038/nrd.2018.183 -
The Lancet. Diabetes & Endocrinology Oct 2021The first insulin preparation capable of consistently lowering blood glucose was developed in 1921. But 100 years later, blood glucose control with insulin in people... (Review)
Review
The first insulin preparation capable of consistently lowering blood glucose was developed in 1921. But 100 years later, blood glucose control with insulin in people with diabetes is nearly universally suboptimal, with essentially the same molecule still delivered by the same inappropriate subcutaneous injection route. Bypassing this route with oral administration appears to have become technologically feasible, accelerating over the past 50 years, either with packaged insulin peptides or by chemical insulin mimetics. Some of the problems of prospective unregulated absorption of insulin into the circulation from subcutaneous depots might be overcome with glucose-responsive insulins. Approaches to these problems could be modification of the peptide by adducts, or the use of nanoparticles or insulin patches, which deliver insulin according to glucose concentration. Some attention has been paid to targeting insulin preferentially to different organs, either by molecular engineering of insulin, or with adducts. But all these approaches still have problems in even beginning to match the responsiveness of physiological insulin delivery to metabolic requirements, both prandially and basally. As would be expected, for all these technically complex approaches, many examples of abandoned development can be found. Meanwhile, it is becoming possible to change the duration of action of subcutaneous injected insulin analogues to act even more rapidly for meals, and towards weekly insulin for basal administration. The state of the art of all these approaches, and the barriers to success, are reviewed here.
Topics: Diabetes Mellitus; Drug Administration Routes; Drug Compounding; Drug Development; History, 20th Century; History, 21st Century; Humans; Insulin; Insulin Infusion Systems
PubMed: 34480874
DOI: 10.1016/S2213-8587(21)00182-0