Methotrexate (MTX) is the first line agent for therapy against rheumatoid arthritis (RA); however, orally its efficacy is hampered by poor solubility, less permeability, short plasma half-life, and reduced bioavailability. Meanwhile, parenteral formulations are associated with severe adverse effects. In an attempt to improve the efficacy of MTX, we synthesized polycaprolactone-polyethylene glycol-polycaprolactone (PCL-PEG-PCL) triblock copolymer by a ring-opening copolymerization reaction and used it as a carrier for the fabrication of MTX-loaded nanomicelles. Surfactant-free, self-assembled nanomicelles were prepared by nanoprecipitation technique and optimized through central composite design. The optimized nanomicelles exhibited a size distribution of 31 nm and an encapsulation efficiency of 91%. In vitro, the nanomicelles exhibited hemocompatibility, sustained release, and significantly high uptake in lipopolysaccharide activated macrophages. To facilitate application on the skin, optimized nanomicelles were loaded into a Carbopol 934-based hydrogel with eucalyptus oil as a penetration enhancer. Eucalyptus oil significantly improved the permeation of nanomicelles through the skin (p < 0.001). When the hydrogel was applied on the RA mice model, nanomicelles exhibited preferentially highest accumulation in the inflamed joints than other organs. As compared with the free MTX, MTX nanomicelles significantly improved the pharmacokinetic (4.34-fold greater half-life, 3.68-fold higher AUC0–t , and 3.15-fold higher mean residence time) and pharmacodynamic profile ascertained through low inflammatory cytokines expression, improved oxidation protection, recovered behavioral responses, and radiological analysis. MTX nanomicelles-based hydrogel also significantly reduced the hepatotoxicity and did not activate the immune system. These results suggest that the MTX-loaded nanomicelles-based transdermal hydrogel can prove to be a promising agent against RA.

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Nanomaterials have found extensive biomedical applications in the past few years because of their small size, low molecular weight, larger surface area, enhanced biological, and chemical reactivity. Among these nanomaterials, nanogels (NGs) are promising drug delivery systems and are composed of cross-linked polymeric nanoparticles ranging from 100 to 200 nm. NGs represent an innovative zone of research with speedy developments taking place on a daily basis. An incredible amount of focus is placed on the fabrication of NGs with novel polymers to achieve better control over the drug release. This review article covers a number of aspects of NGs including their types, associated pros and cons, and methods of preparation along with technical and economical superiority and therapeutic efficacy over each other. The last part of review summarizes the applications of NGs in the drug delivery and treatment of various diseases including brain disease, cardiovascular diseases, oxidative stress, diabetes, cancer therapy, tissue engineering, gene therapy, inflammatory disorders, pain management, ophthalmic and autoimmune diseases, and their future challenges. NGs appear to be an outstanding nominee for drug delivery systems, and further study is required to explore their interactions at the cellular and molecular levels.

As heterocyclic macrocycle organic compounds, porphyrins can generate a rich platform of chemical behavior and characteristics conveniently utilized for multiple bioapplications, including bio‐sensors, fluorescence tracking, and in vivo imaging. The conjugation of nanotechnology and porphyrins presents a promising approach to enhance the safety and effectiveness of porphyrin‐based materials in phototherapy against cancer. Several nanoformulations, including organic and inorganic nanocarriers, porphyrin‐laden nanoparticles, porphyrin‐based amphiphilic molecules, supramolecular polymers, and porphyrin‐based block copolymers, have been investigated to deliver porphyrins, which protect the pre‐mature release of photosensitizer and provide tumor‐selective and site‐specific targeting. The monodisperse nanoparticles formed of biocompatible building block conjugates can be beneficially used to develop a multifunctional novel system utilized in optical imaging, positron emission tomography, photodynamic therapy, photothermal therapy, and other imaging modalities in one formulation. This topic is important because exploiting and knowing porphyrin‐based nanostructures aids in detecting pathological damages that cannot readily be discovered by routine imaging or physical examination and thus, helps early diagnosis of cancer. This critical review will assess the basic knowledge and updated information for a broad audience of scientists, engineers, and newcomers related to the porphyrin‐based nanostructures for cancer theranostics