Concept: Route of administration
The efficacy of antiretroviral therapy is significantly compromised by medication non-adherence. Long-acting enteral systems that can ease the burden of daily adherence have not yet been developed. Here we describe an oral dosage form composed of distinct drug-polymer matrices which achieved week-long systemic drug levels of the antiretrovirals dolutegravir, rilpivirine and cabotegravir in a pig. Simulations of viral dynamics and patient adherence patterns indicate that such systems would significantly reduce therapeutic failures and epidemiological modelling suggests that using such an intervention prophylactically could avert hundreds of thousands of new HIV cases. In sum, weekly administration of long-acting antiretrovirals via a novel oral dosage form is a promising intervention to help control the HIV epidemic worldwide.
Current arthritis treatments often have side-effects attributable to active compounds as well as route of administration. Cannabidiol (CBD) attenuates inflammation and pain without side-effects, but CBD is hydrophobic and has poor oral bioavailability. Topical drug application avoids gastrointestinal administration, first pass metabolism, providing more constant plasma levels.
OBJECTIVE: To compare the effects of continuous use of oral (OC), transdermal, and vaginal combined contraceptives on the pituitary-ovarian axis and inhibition of follicular development. DESIGN: Spin-off study of a prospective, randomized trial. SETTING: University clinic. PATIENT(S): Forty-two of 54 healthy women completed the study. INTERVENTION(S): Treatment with combined OCs (ethinyl E(2) [EE] and desogestrel), transdermal patches (EE and norelgestromin), or vaginal rings (EE and etonogestrel) for 9 weeks continuously. Blood sampling was performed before and at 5 and 9 weeks of treatment. MAIN OUTCOME MEASURE(S): Changes in serum hormone levels induced by combined contraceptives. RESULT(S): Serum antimüllerian hormone (AMH), FSH, inhibin B, LH, and E(2) levels had decreased significantly in all study groups after 9 weeks of treatment. Significant declines were already detected after 5 weeks' use of combined contraceptives with regard to all hormone levels apart from those of serum AMH, where the decrease between baseline and 5 weeks was only moderate. Between groups, serum levels of AMH, inhibin B, LH, and E(2) were comparable at baseline and after 5 and 9 weeks of treatment. CONCLUSION(S): The decrease of serum AMH levels during the use of all combined contraceptives indicates that folliculogenesis is arrested independently of administration route. CLINICAL TRIAL REGISTRATION NUMBER: NCT01087879.
- Journal of controlled release : official journal of the Controlled Release Society
- Published about 5 years ago
This review provides the first comprehensive overview of the use of both nanoparticles and nanofibers for topical drug delivery. Researchers have explored the use of nanotechnology, specifically nanoparticles and nanofibers, as drug delivery systems for topical and transdermal applications. This approach employs increased drug concentration in the carrier, in order to increase drug flux into and through the skin. Both nanoparticles and nanofibers can be used to deliver hydrophobic and hydrophilic drugs and are capable of controlled release for a prolonged period of time. The examples presented provide significant evidence that this area of research has - and will continue to have - a profound impact on both clinical outcomes and the development of new products.
To assess the pharmacokinetic properties of community-use formulations of naloxone for emergency treatment of opioid overdose.
Parenterally administered ascorbic acid modulates sepsis-induced inflammation and coagulation in experimental animal models. The objective of this randomized, double-blind, placebo-controlled, phase I trial was to determine the safety of intravenously infused ascorbic acid in patients with severe sepsis.
To secure a polio-free world, the live attenuated oral poliovirus vaccine (OPV) will eventually need to be replaced with inactivated poliovirus vaccines (IPV). However, current IPV delivery is less suitable for campaign use than OPV, and more expensive. We are progressing a microarray patch delivery platform, the Nanopatch, as an easy-to-use device to administer vaccines, including IPV. The Nanopatch contains an ultra-high density array (10,000/cm(2)) of short (~230 μm) microprojections that delivers dry coated vaccine into the skin. Here, we compare the relative immunogenicity of Nanopatch immunisation versus intramuscular injection in rats, using monovalent and trivalent formulations of IPV. Nanopatch delivery elicits faster antibody response kinetics, with high titres of neutralising antibody after just one (IPV2) or two (IPV1 and IPV3) immunisations, while IM injection requires two (IPV2) or three (IPV1 and IPV3) immunisations to induce similar responses. Seroconversion to each poliovirus type was seen in 100% of rats that received ~1/40th of a human dose of IPV delivered by Nanopatch, but not in rats given ~1/8th or ~1/40th dose by IM injection. Ease of administration coupled with dose reduction observed in this study suggests the Nanopatch could facilitate inexpensive IPV vaccination in campaign settings.
The comprehensive treatment of pain is multidimodal, with pharmacotherapy playing a key role. An effective therapy for pain depends on the intensity and type of pain, the patients' age, comorbidities, and appropriate choice of analgesic, its dose and route of administration. This review is aimed at presenting current knowledge on analgesics administered by transdermal and topical routes for physicians, nurses, pharmacists, and other health care professionals dealing with patients suffering from pain. Analgesics administered transdermally or topically act through different mechanisms. Opioids administered transdermally are absorbed into vessels located in subcutaneous tissue and, subsequently, are conveyed in the blood to opioid receptors localized in the central and peripheral nervous system. Non-steroidal anti-inflammatory drugs (NSAIDs) applied topically render analgesia mainly through a high concentration in the structures of the joint and a provision of local anti-inflammatory effects. Topically administered drugs such as lidocaine and capsaicin in patches, capsaicin in cream, EMLA cream, and creams containing antidepressants (i.e., doxepin, amitriptyline) act mainly locally in tissues through receptors and/or ion channels. Transdermal and topical routes offer some advantages over systemic analgesic administration. Analgesics administered topically have a much better profile for adverse effects as they relieve local pain with minimal systemic effects. The transdermal route apart from the above-mentioned advantages and provision of long period of analgesia may be more convenient, especially for patients who are unable to take drugs orally. Topically and transdermally administered opioids are characterised by a lower risk of addiction compared to oral and parenteral routes.
Despite the fact that magnetic thrombolytic composites is an emerging area, all known so far systems are based on the similar mechanism of action: thrombolytic enzyme releases from the magnetic carrier leaving non-active matrix, thus making the whole system active only for a limited period of time. Such systems often have very complex structure organization and composition, consisting of materials not approved for parenteral injection, making them poor candidates for real clinical trials and implementation. Here we report, for the first time, the production of thrombolytic magnetic composite material with non-releasing behavior and prolonged action. Obtained composite shows good thrombolytic activity, consists of fully biocompatible materials and could be applied as infinitely active thrombolytic coatings or magnetically-targetable thrombolytic agents.
To evaluate the efficacy of anti-VEGF agents for treating choroidal neovascularization (CNV) when delivered topically using novel cell-penetrating peptides (CPPs) compared with delivery by intravitreal (ivit) injection.