Poly(lactic-co-glycolic acid) (PLGA) is the most widely used biomaterial for microencapsulation and prolonged delivery of therapeutic drugs, proteins and antigens. PLGA has excellent biodegradability and biocompatibility and is generally recognized as safe by international regulatory agencies including the United States Food and Drug Administration and the European Medicines Agency. The physicochemical properties of PLGA may be varied systematically by changing the ratio of lactic acid to glycolic acid. This in turn alters the release rate of microencapsulated therapeutic molecules from PLGA microparticle formulations. The obstacles hindering more widespread use of PLGA for producing sustained-release formulations for clinical use include low drug loading, particularly of hydrophilic small molecules, high initial burst release and/or poor formulation stability. In this review, we address strategies aimed at overcoming these challenges. These include use of low-temperature double-emulsion methods to increase drug-loading by producing PLGA particles with a small volume for the inner water phase and a suitable pH of the external phase. Newer strategies for producing PLGA particles with high drug loading and the desired sustained-release profiles include fabrication of multi-layered microparticles, nanoparticles-in-microparticles, use of hydrogel templates, as well as coaxial electrospray, microfluidics and supercritical carbon dioxide methods. Another recent strategy with promise for producing particles with well-controlled and reproducible sustained-release profiles involves complexation of PLGA with additives such as polyethylene glycol, poly(ortho esters), chitosan, alginate, caffeic acid, hyaluronic acid and silicon dioxide.

Low back pain (LBP) is the world’s leading cause of disability and is increasing in prevalence more rapidly than any other pain condition. Intervertebral disc (IVD) degeneration and facet joint osteoarthritis (FJOA) are two common causes of LBP, and both occur more frequently in elderly women than in other populations. Moreover, osteoarthritis (OA) and OA pain, regardless of the joint, are experienced by up to twice as many women as men, and this difference is amplified during menopause. Changes in estrogen may be an important contributor to these pain states. Receptors for estrogen have been found within IVD tissue and nearby joints, highlighting the potential roles of estrogen within and surrounding the IVDs and joints. In addition, estrogen supplementation has been shown to be effective at ameliorating IVD degeneration and OA progression, indicating its potential use as a therapeutic agent for people with LBP and OA pain. This review comprehensively examines the relationship between estrogen and these pain conditions by summarizing recent preclinical and clinical findings. The potential molecular mechanisms by which estrogen may relieve LBP associated with IVD degeneration and FJOA and OA pain are discussed.

Many studies show that glucose metabolism in epileptic brain areas can be impaired. Energy is crucial to maintain normal brain function, including ion and neurotransmitter balances. Energy deficits can lead to disruption of ion gradients, which can trigger neuronal depolarization and generation of seizures. Thus, perturbed metabolic processing of glucose in epileptogenic brain areas indicates a specific nutritional need for people and animals with epilepsy, as they are likely to benefit from auxiliary brain fuels other than glucose. Ketogenic diets provide the ketone bodies acetoacetate and β‐hydroxybutyrate, which can be used as auxiliary fuel by the brain. In approximately 50% children and adults with certain types of epilepsy, who can tolerate and maintain these dietary regimens, seizure frequency can be effectively reduced. More recent data demonstrate that addition of medium chain triglycerides (MCTs), which provide the medium chain fatty acids octanoic and decanoic acid, as well as ketone bodies as auxiliary brain energy, can be beneficial in rodent seizure models, and dogs and humans with epilepsy. Here, this evidence is reviewed, including tolerance in 65% of humans, efficacy studies in dogs, possible anticonvulsant mechanisms of actions of MCTs, and specifically decanoic acid as well as metabolic and antioxidant mechanisms. In conclusion, MCTs are a promising adjunct to standard pharmacological treatment for both humans and dogs with epilepsy, as they lack central nervous system side effects found with current antiepileptic drugs. There is now a need for larger clinical trials in children, adults, and dogs to find the ideal composition and doses of MCTs and the types of epilepsy that respond best.

Poly(lactic-co-glycolic acid) (PLGA) nanoparticles have been extensively studied as carriers of a wide variety of drugs. However, the variability in protocols and reporting in nanoscience represents a barrier to advances in new therapies. Recent literature has highlighted the challenge of reproducibility in biomedical research. In this study involving three researchers performing the experiments we therefore verified the repeatability and replicability of PLGA nanoparticles fabricated by the emulsion solvent evaporation method. Furthermore, we investigated how variables during synthesis, isolation, and characterisation of PLGA particles affect the reported particle size and drug encapsulation. Synthesis parameters including emulsification technique, type of polymer, and type of surfactant were investigated. In the isolation process, we tested the effect of washing and filtration. Dynamic light scattering (DLS) was used to determine the number weighted mean, z-average, and polydispersity index (PDI). Direct visualization of the particles was achieved by scanning and transmission electron microscopies. Changes in the source of energy input to the system using a sonic probe and homogeniser showed the most pronounced effect on particle size and PDI. This work has demonstrated that particle properties are affected by multiple variables involved in the synthesis and isolation processes. We provided advice for PLGA-based nanoparticle fabrication and drug encapsulation quantification as well as the minimum required information to be reported allowing reproducibility.