Anti-inflammatory therapy enables robot-actuated regeneration of aged muscle.

Robot-actuated mechanical loading (ML)-based therapies ("mechanotherapies") can promote regeneration after severe skeletal muscle injury, but the effectiveness of such approaches during aging is unknown and may be influenced by age-associated decline in the healing capacity of skeletal muscle. To address this knowledge gap, this work used a noninvasive, load-controlled robotic device to impose highly defined tissue stresses to evaluate the age dependence of ML on muscle repair after injury. The response of injured muscle to robot-actuated cyclic compressive loading was found to be age sensitive, revealing not only a lack of reparative benefit of ML on injured aged muscles but also exacerbation of tissue inflammation. ML alone also disrupted the normal regenerative processes of aged muscle stem cells. However, these negative effects could be reversed by introducing anti-inflammatory therapy alongside ML application, leading to enhanced skeletal muscle regeneration even in aged mice.

Bioadhesive dosage form for peroral administration of timolol base.

Timolol base was prepared from its maleate salt and checked for purity, pKa (9.03) and n-octanol/phosphate buffer pH 6.6 partition coefficient (1.72). The rate of swelling of sodium carboxymethylcellulose, Carbopol 934 (CP) and hydroxypropylcellulose (HPC) was examined prior to use in bioadhesive compacts with the model drug methylene blue to study their influence on device integrity and drug diffusion. A final compact containing a core of timolol base and Precirol, a bioadhesive layer of CP and HPC, and a cap of magnesium stearate gave sustained release of the drug in simulated saliva pH 6.6. After preliminary evaluation in dogs, the compact was evaluated in a panel of humans in whom it was shown that the flux of drug could be increased from 70 to 127 micrograms mm-2 h-1 by inclusion of the penetration enhancer sodium lauryl-sulphate into the core formulation.