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Expert Opinion on Drug Delivery Jul 2014Polymer-drug conjugates are an important part of polymer therapeutics. Recently, they have been used as an appealing platform for drug delivery. As a delivery vector,... (Review)
Review
INTRODUCTION
Polymer-drug conjugates are an important part of polymer therapeutics. Recently, they have been used as an appealing platform for drug delivery. As a delivery vector, the route of administration performs a serious impact on the accessibility of drug molecules to their respective target site and therapeutic index. Furthermore, the physicochemical and biological properties of conjugates also correlate distinctly with the route of administration.
AREAS COVERED
This article reviews the recent advances of polymer-drug conjugates as drug delivery systems through parenteral, enteral and topical routes. In particular, it mainly focuses on the classical and emerging routes such as injection, oral, transdermal, pulmonary and ocular routes using polymer-drug conjugates as delivery systems.
EXPERT OPINION
Although polymer-conjugated drug delivery systems reported so far face severe shortcoming of being incomplete methodology and limited routes for administration (mostly concentrated in injection), some polymer carriers like poly(amidoamine) and hyaluronic acid still offer an appealing platform to deliver drug. Acquiring the particular characteristics of each polymer carrier, exploiting novel biodegradable polymer, expanding classical drug administration ways by emerging routes and developing a rational and systematic methodology to design administration routes will be the promising directions.
Topics: Animals; Chemistry, Pharmaceutical; Drug Administration Routes; Drug Delivery Systems; Humans; Pharmaceutical Preparations; Polymers
PubMed: 24758250
DOI: 10.1517/17425247.2014.912779 -
Journal of Women's Health (2002) 2005Mechanistic investigations into the physiological and biochemical differences between patients have only recently begun to help explain what was previously categorized... (Review)
Review
Mechanistic investigations into the physiological and biochemical differences between patients have only recently begun to help explain what was previously categorized as "intersubject variability." Additional factors, including the particular drug formulation or delivery system, have been implicated in observed sex-based and race-based differences in pharmacokinetic response. Drug absorption following intramuscular injection can be highly variable if the injection is mistakenly placed in the overlying tissues, a situation that is more likely to occur in women than men. Slower gastric emptying in women can significantly delay the onset of effectiveness of enteric-coated dosage forms, and differences in gastric pH can affect the drug solubility and dissolution rate. Slower drug release rates designed into many extended release dosage forms interact with the differential locations and populations of intestinal and hepatic transporters and metabolizing enzymes to cause significant sex-based and race-based differences in plasma drug concentrations. Increased efforts to identify and understand the interplay of an individual's physiological makeup, dietary intake, environment, and the drug products he or she uses are needed to be able to provide optimal drug therapy regimens to each patient.
Topics: Biological Availability; Biological Transport; Dose-Response Relationship, Drug; Drug Administration Routes; Drug Delivery Systems; Drug Prescriptions; Evidence-Based Medicine; Female; Humans; Pharmacokinetics; Racial Groups; Sex Characteristics; United States; Women's Health
PubMed: 15692275
DOI: 10.1089/jwh.2005.14.30 -
Therapeutic Delivery Jul 2017Drug delivery to the posterior segment via the periocular route is a promising route for delivery of a range of formulations. In this review, we have highlighted the... (Review)
Review
Drug delivery to the posterior segment via the periocular route is a promising route for delivery of a range of formulations. In this review, we have highlighted the challenges and opportunities of posterior segment drug delivery via the periocular route. Consequently, we have discussed different types of periocular routes, physiological barriers that limit effective drug delivery, practical challenges regarding patient compliance and acceptability and recent advances in developing innovative strategies to enhance periocular drug delivery. We conclude with a perspective on how we envisage the importance of understanding complex barrier functions so as to continue to develop innovative drug-delivery systems.
Topics: Administration, Ophthalmic; Drug Delivery Systems; Eye Diseases; Humans
PubMed: 28730942
DOI: 10.4155/tde-2017-0097 -
Climacteric : the Journal of the... Aug 2005This review comprises the pharmacokinetics and pharmacodynamics of natural and synthetic estrogens and progestogens used in contraception and therapy, with special... (Review)
Review
This review comprises the pharmacokinetics and pharmacodynamics of natural and synthetic estrogens and progestogens used in contraception and therapy, with special consideration of hormone replacement therapy. The paper describes the mechanisms of action, the relation between structure and hormonal activity, differences in hormonal pattern and potency, peculiarities in the properties of certain steroids, tissue-specific effects, and the metabolism of the available estrogens and progestogens. The influence of the route of administration on pharmacokinetics, hormonal activity and metabolism is presented, and the effects of oral and transdermal treatment with estrogens on tissues, clinical and serum parameters are compared. The effects of oral, transdermal (patch and gel), intranasal, sublingual, buccal, vaginal, subcutaneous and intramuscular administration of estrogens, as well as of oral, vaginal, transdermal, intranasal, buccal, intramuscular and intrauterine application of progestogens are discussed. The various types of progestogens, their receptor interaction, hormonal pattern and the hormonal activity of certain metabolites are described in detail. The structural formulae, serum concentrations, binding affinities to steroid receptors and serum binding globulins, and the relative potencies of the available estrogens and progestins are presented. Differences in the tissue-specific effects of the various compounds and regimens and their potential implications with the risks and benefits of hormone replacement therapy are discussed.
Topics: Drug Administration Routes; Estrogen Replacement Therapy; Estrogens; Female; Humans; Progestins
PubMed: 16112947
DOI: 10.1080/13697130500148875 -
European Journal of Mass Spectrometry... 2013During the last decade, significant technological improvements in mass spectrometry have had a great impact on drug discovery. The development of matrix-assisted laser...
During the last decade, significant technological improvements in mass spectrometry have had a great impact on drug discovery. The development of matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) has set a new frontier for the study of the distribution of endogenous and exogenous molecules present within a tissue. MALDI-IMS is a surface sampling technique that allows not only the detection of multiple analytes but also gives the spatial distribution of those analytes. Active compounds for pulmonary disease need an optimal and well-studied delivery into the lungs, in order to assure distribution with greater penetration into the peripheral or the alveolar region of the lung to maximize the therapeutic effects. IMS is very useful in the field of drug discovery, showing drug delivery and distribution in the body and organs. In this study, we present a comparison between two different ways of carrying out pulmonary drug administration: inhalation of a nebulized aerosol of aqueous drug solutions and intratracheal administration, which is much simpler, not expensive and commonly used during in vivo screening. Tiotropium bromide is a long-acting anticholinergic medicine used for maintenance treatment of chronic obstructive pulmonary disease. In the present work, tiotropium was administered by nebulization and by intratracheal instillation to guinea pigs at doses able to induce significant anti-bronchoconstrictive activity. Lung samples were dissected, frozen, cryosectioned and coated with matrix (α-hydroxy-cinnamic acid). IMS analyses were performed using a MALDI-LTQ-Orbitrap XL. Using this technique we were able to compare different distributions of the drug depending on the method of administration.
Topics: Administration, Inhalation; Aerosols; Animals; Cholinergic Antagonists; Drug Administration Routes; Drug Delivery Systems; Drug Discovery; Guinea Pigs; Lung; Male; Nebulizers and Vaporizers; Pulmonary Disease, Chronic Obstructive; Scopolamine Derivatives; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Tiotropium Bromide; Tissue Distribution
PubMed: 24378465
DOI: 10.1255/ejms.1254 -
Journal of Pharmaceutical Sciences Oct 2017An increasing number of therapeutic proteins are being developed for delivery through the subcutaneous (SC) route of administration. Relative to intravenous (IV)... (Review)
Review
An increasing number of therapeutic proteins are being developed for delivery through the subcutaneous (SC) route of administration. Relative to intravenous (IV) administration, the SC route offers more convenience to patients, flexibility in dosing, and potential to reduce health care costs. There is a perception that SC administration can pose a higher immunogenicity risk than IV administration for a given protein. To evaluate whether there is a difference in therapeutic protein immunogenicity associated with administration routes, a more detailed understanding of the interactions with the immune system by each route is needed. Few approved therapeutic proteins have available clinical immunogenicity data sets in the public domain that represent both IV and SC administration routes. This has prevented a direct comparison of the 2 routes of administration across a large sample size. Of the 6 marketed products where SC and IV route-related incidences of anti-drug antibody (ADA) were available, 4 were associated with higher immunogenicity incidence with SC. In other cases, there was no apparent difference between the SC and IV routes. Overall, the ADA incidence was low (<15%) with no impact on safety or efficacy. The challenges associated with identifying specific risk factors unique to SC administration are discussed.
Topics: Administration, Intravenous; Animals; Antibodies; Antibody Formation; Humans; Injections, Intravenous; Injections, Subcutaneous; Proteins; Risk Factors
PubMed: 28576695
DOI: 10.1016/j.xphs.2017.05.030 -
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 -
Revista de Enfermeria (Barcelona, Spain) Jan 2015To achieve well-being in patients in Palliative Care is required to know which are the most common symptoms, which are the drugs used for relief, which are the routes of... (Review)
Review
OBJECTVE
To achieve well-being in patients in Palliative Care is required to know which are the most common symptoms, which are the drugs used for relief, which are the routes of administration of drugs that are suitable, how effective the drugs are and what incompatibilities, interactions and adverse effects occur. The aim of this article is to review the relevant issues in the management of the drugs commonly used by nursing in Palliative Care and presenting recommendations to clinical practice.
METHODOLOGY
Management interventions drugs for nurses in Palliative Care recommended by the scientific literature after a search of Scopus, CINAHL, Medline, PubMed, UpToDate and Google Scholar are selected.
RESULTS
The oral route is the choice for patients in palliative situation and subcutaneous route when the first is not available. The symptoms, complex, intense and moody, should be systematically reevaluated by the nurse, to predict when a possible decompensation of it needing extra dose of medication.
DISCUSSION
Nurses must be able to recognize the imbalance of well-being and act quickly and effectively, to get relief to some unpleasant situations for the patient as the pain symptoms, dyspnea or delirium. For the proper administration of rescue medication, the nurse should know the methods of symptomatic evaluation, pharmacokinetics and pharmacodynamics of drugs, the time intervals to elapse between different rescues and nccocc rocnnnco t thocm
Topics: Drug Administration Routes; Drug Interactions; Drug Therapy; Humans; Infusions, Subcutaneous; Palliative Care; Practice Guidelines as Topic
PubMed: 26540909
DOI: No ID Found -
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 -
Addiction (Abingdon, England) Dec 1999
Topics: Drug Administration Routes; Humans; Illicit Drugs; Substance-Related Disorders; United Kingdom
PubMed: 10717956
DOI: 10.1080/09652149932262