Efficacy and safety of a diffusion-based extended-release fluticasone propionate intra-articular injection (EP-104IAR) in knee osteoarthritis (SPRINGBOARD): a 24-week, multicentre, randomised, double-blind, vehicle-controlled, phase 2 trial.

Background: Corticosteroids are among the few effective treatments for knee osteoarthritis, but short duration of action limits their utility. EP-104IAR, a long-acting formulation of fluticasone propionate for intra-articular injection, optimises the action of fluticasone propionate through novel diffusion-based extended-release technology. The SPRINGBOARD trial assessed the efficacy, safety, and pharmacokinetics of EP-104IAR in people with knee osteoarthritis.

Safety and pharmacokinetics of EP-104IAR (sustained-release fluticasone propionate) in knee osteoarthritis: A randomized, double-blind, placebo-controlled phase 1 trial.

Objective: EP-104IAR is a novel, sustained-release, intra-articular (IA) formulation of the corticosteroid fluticasone propionate (FP), in development for the treatment of osteoarthritis (OA) pain. This study evaluated the safety, pharmacokinetics (PK) and efficacy of a single dose of EP-104IAR in patients with OA of the knee.

Design: This was a multi-center, randomized, double-blind, placebo-controlled trial performed at 3 sites in Canada.

The Figure-of-8 Walk Test used to detect the loss of motor skill in walking among persons with Parkinson's disease.

Background: The Figure-of-8 Walk Test (F8W) is a valid measure of walking skill in older adults with a mobility disability. Use of the F8W in assessing walking skill in persons with Parkinson's disease (PWP) is unknown.

Purpose: We examined the validity of the F8W by associations with mobility, and cognitive and physical function, and determined the ability of the F8W to discriminate the motor skill of walking in PWP from that of older adults (OA).

Determination of knee cartilage volume and surface area in beagle dogs: a pilot study.

Background: The objective of this study was to determine the cartilage volume and surface area of male and female Beagle dog knees using 3D (3 dimensional) reconstructed MRI images.

Methods: Six Beagle Dogs (Canis familiaris) (3 males and 3 females) of 10-18 months old and weighing between 7.2 and 17.

Pharmacokinetic Profile of Intra-articular Fluticasone Propionate Microparticles in Beagle Dog Knees.

Objective: The objective of this pilot study was to determine time point(s) at which maximum concentration of fluticasone propionate (Cmax) occurs in synovial fluid and plasma in Beagle dog knees after intra-articular injection of EP-104IAR.

Design: EP-104IAR is composed of fluticasone propionate drug crystals coated with heat-treated polyvinyl alcohol (PVA) to result in extended release properties. Thirty-two Beagle dogs had an injection of EP-104IAR into the knee joint at 2 different dose levels (0.

Pharmacokinetics of a multipurpose pod-intravaginal ring simultaneously delivering five drugs in an ovine model.

Multipurpose technologies that simultaneously protect from sexually transmitted infections and unintended pregnancy are urgently needed. Pod-intravaginal rings (IVRs) formulated with the antiretroviral agents (ARVs) tenofovir, nevirapine, and saquinavir and the contraceptives etonogestrel and estradiol were evaluated in sheep. Steady-state concentrations were maintained for 28 days with controlled, sustained delivery.

Safety and pharmacokinetics of intravaginal rings delivering tenofovir in pig-tailed macaques.

Antiretroviral-based microbicides applied topically to the vagina may play an important role in protecting women from HIV infection. Incorporation of the nucleoside reverse transcriptase inhibitor tenofovir (TFV) into intravaginal rings (IVRs) for sustained mucosal delivery may lead to increased microbicide product adherence and efficacy compared with those of conventional vaginal formulations. Formulations of a novel "pod IVR" platform spanning a range of IVR drug loadings and daily release rates of TFV were evaluated in a pig-tailed macaque model.

An intravaginal ring for the simultaneous delivery of multiple drugs.

Intravaginal delivery of microbicide combinations is a promising approach for the prevention of sexually transmitted infections, but requires a method of providing simultaneous, independent release of multiple agents into the vaginal compartment. A novel intravaginal ring (IVR) platform has been developed for simultaneous delivery of the reverse-transcriptase inhibitor tenofovir (TFV) and the guanosine analogue antiviral acyclovir (ACV) with independent control of release rate for each drug. The IVR is based on a pod design, with up to 10 individual polymer-coated drug cores embedded in the ring releasing through preformed delivery channels.

Tenofovir and tenofovir disoproxil fumarate pharmacokinetics from intravaginal rings.

Objectives: To compare the distribution of tenofovir in sheep vaginal lumen, tissue, and plasma following topical delivery of the antiretroviral drug from intravaginal rings, either as tenofovir or the disoproxil fumarate prodrug.

Design: Comparative pharmacokinetic study in sheep.

Method: Intravaginal rings formulated to achieve equivalent release rates of tenofovir and its disoproxil fumarate prodrug were evaluated for 28 days in sheep, with four animals in each group.

Simultaneous delivery of tenofovir and acyclovir via an intravaginal ring.

Vaginal microbicides may play an important role in protecting women from HIV infection. A strong synergy between HSV and HIV has been observed, and epidemiological studies demonstrate that HSV infection increases the risk of HIV acquisition. Incorporation of the antiretroviral tenofovir (TFV) along with the antiherpetic acyclovir (ACV) into combination intravaginal rings (IVRs) for sustained mucosal delivery of both compounds could lead to increased microbicide product adherence and efficacy compared with conventional vaginal formulations.

Microbial biofilms on the surface of intravaginal rings worn in non-human primates.

Millions of intravaginal rings (IVRs) are used by women worldwide for contraception and for the treatment of vaginal atrophy. These devices also are suitable for local and systemic sustained release drug delivery, notably for antiviral agents in human immunodeficiency virus pre-exposure prophylaxis. Despite the widespread use of IVRs, no studies have examined whether surface-attached bacterial biofilms develop in vivo, an important consideration when determining the safety of these devices.

Osteocytes as mechanosensors in the inhibition of bone resorption due to mechanical loading.

Bone has the ability to adjust its structure to meet its mechanical environment. The prevailing view of bone mechanobiology is that osteocytes are responsible for detecting and responding to mechanical loading and initiating the bone adaptation process. However, how osteocytes signal effector cells and initiate bone turnover is not well understood.

Primary cilia mediate mechanosensing in bone cells by a calcium-independent mechanism.

Primary cilia are sensory organelles that translate extracellular chemical and mechanical cues into cellular responses. Bone is an exquisitely mechanosensitive organ, and its homeostasis depends on the ability of bone cells to sense and respond to mechanical stimuli. One such stimulus is dynamic fluid flow, which triggers biochemical and transcriptional changes in bone cells by an unknown mechanism.

The role of actin cytoskeleton in oscillatory fluid flow-induced signaling in MC3T3-E1 osteoblasts.

Fluid flow due to loading in bone is a potent mechanical signal that may play an important role in bone adaptation to its mechanical environment. Previous in vitro studies of osteoblastic cells revealed that the upregulation of cyclooxygenase-2 (COX-2) and c-fos induced by steady fluid flow depends on a change in actin polymerization dynamics and the formation of actin stress fibers. Exposing cells to dynamic oscillatory fluid flow, the temporal flow pattern that results from normal physical activity, is also known to result in increased COX-2 expression and PGE(2) release.

Effects of short-term recovery periods on fluid-induced signaling in osteoblastic cells.

It is well known that cyclic mechanical loading can produce an anabolic response in bone. In vivo studies have shown that the insertion of short-term recovery periods (10-15 s) into mechanical loading profiles led to an increased osteogenic response compared to continuous cyclic loading of bone. Although this is suggestive of temporal processing at the bone cell level, there is little evidence to support such a hypothesis.