The intra-articular administration of conventional drug solutions or dispersions in joint diseases such as osteoarthritis has a relatively short retention time and, therefore, limited therapeutic effect. Thermosensitive polymer solutions that exhibit a sol–gel phase transition near body temperature after injection can prolong drug retention by providing a depot from which the drug release is sustained while relieving inflammation and preventing degradation of the joint complex. Thermosensitive hydrogels have in recent times garnered considerable attention in the intra-articular therapeutics of joint diseases such as osteoarthritis. Among the stimuli-responsive gelling systems, most research has focused on thermosensitive hydrogels. These gels are preferred over other stimuli-sensitive hydrogels since they have well-controlled in situ gelling properties and are also easier to load with drugs. Temperature-sensitive polymers, such as block copolymers or poloxamers, are frequently used to modify their gelation properties, usually in combination with other polymers. They are compatible with most drugs but may pose formulation challenges in terms of their low-response time, highly fragile nature, and low biocompatibility. The stability and biodegradability of implant hydrogels can control the drug release rate and treatment efficacy. This review stresses the application of thermosensitive gels in joint disorders and summarizes recent developments for intra-articular application, including the incorporation of nanoparticles. The hydrogel composition, drug release mechanisms, and the challenges involved in their formulation and storage are also discussed.

Glioblastoma (GBM), the most prevalent brain tumor, is one of the least treatable malignancies due to its propensity for intracranial spread, high proliferative potential, and innate resistance to radiation and chemotherapy. Current GBM therapy is limited due to unfavorable, non-specific therapeutic effects in healthy cells and the difficulty of small molecules to penetrate the blood brain barrier (BBB) and reach the tumor microenvironment. Adding PARP-1 inhibitors inhibit DNA repair enzymes thereby increasing the cytotoxicity of anticancer agents. Hence, we aimed to discover potential naturally occurring PARP-1 inhibitors that can be utilized in the treatment of glioma by using multiple in silico tools like molecular docking, absorption, distribution, metabolism, and excretion (ADME) profile, pharmacophore modeling, and molecular dynamic (MD) simulations. Among 43 phytocompounds we screened, two of them (Ellagic acid and Naringin) were discovered to be bound to the catalytic site of PARP-1 with an affinity more remarkable than commercially available PARP-1 inhibitors (Talazoparib, Niraparib, and Rucaparib) except Olaparib. The molecular interactions were analyzed, and data shows that bound entity attained a conserved domain via hydrogen bond interactions, polar interactions, and π-π stacking. Pharmacophore modeling studies showed electronic and steric features of ligands responsible for supramolecular interaction with PARP-1. ADME properties were studied, to assess drug-likeness, hydrophilic nature, hydrophobicity, brain permeability, and oral bioavailability of the natural PARP-1 inhibitors. The simulation study demonstrated the development of a stable complex between Naringin, Ellagic acid, and PARP-1 protein. Moreover, cell culture studies and animal investigations are essential to determine pharmacokinetics and pharmacodynamics.

The Indian system of medicine, Ayurveda employs Bacopa monnieri extract (BME) for memory enhancement. This study attempts to prepare and test a more potent formulation by incorporating BME in nanovesicles. BME-loaded liposomes and bilosomes (bile salt-stabilized liposomes) were formulated using soy phosphatidylcholine. Liposomes and bilosomes had homogeneous size distribution and an average size of 285.7 nm and 84 nm, respectively, with satisfactory zeta potential. Spherical multilamellar bilosomes and unilamellar liposomes were observed under transmission electron microscope (TEM), with BME entrapment efficiency of 85% and 45%, respectively. During a 72 h interval, bilosomes and liposomes released 78% and 65% of the loaded BME, exhibiting a biphasic release, following the Higuchi model diffusion. Both liposomes and bilosomes were stable in simulated gastric and intestinal fluids. When tested on dementia-induced Swiss albino mouse models using the Y-maze apparatus, the bilosome-treated group showed significant cognition enhancement activity than those treated with liposomal vesicles. The better pharmacological effect shown by bilosomes may be attributed to better bioavailability, possibly augmented by higher entrapment efficiency, and improved vesicle integrity afforded by bile salts. Likewise, bilosomes were more stable than liposomes in simulated gastric and intestinal fluids. Taken together, innovative formulation techniques hold substantial promise for enhancing the ethnopharmacological claims of BME.