Triple drug co-delivery within nanosystems for synergistic anti-infective, anti-inflammatory, antinociceptive and neuroregenerative therapeutic effects: a focus on pharmacological and nanotechnological aspects.

Nanotechnology has emerged as an innovative tool capable of overcoming the limitations of traditional drug delivery systems, by enabling enhanced drug solubility and stability, controlled drug release, and improved drug targeting. Additionally, nanosystems can allow the co-encapsulation of multiple drugs simultaneously, harnessing their synergistic pharmacological effects, leading to increased therapeutic efficacy and safety. The purpose of this review is to critically analyze studies that have developed triple drug-loaded nanosystems, exploring various different nanoplatforms, such as polymeric nanoparticles, lipid nanoparticles, microcapsules, nanoemulsions, nanoemulgels, thermosensitive hydrogels, and nanocomposite hydrogels. Triple drug co-encapsulation has been achieved for non-steroidal anti-inflammatory drugs such as indomethacin, analgesic and antipyretic drugs such as paracetamol, immunosuppressant drugs such as methotrexate, antiretroviral drugs such as efavirenz, lopinavir, ritonavir, and tenofovir, antibacterial drugs such as amoxicillin and clarithromycin, antiulcer drugs such as omeprazole and famotidine, ion channel antagonists such as lomerizine hydrochloride, oxidized adenosine triphosphate, and zonampanel monohydrate, photosensitive molecules such as indocyanine green, genetic material such as MMP-9 siRNA, enzymes such as catalase, and/or plant-derived bioactive compounds such as curcumin, resveratrol, sinomenine, and thymoquinone. These molecules' triple co-encapsulation into nanometric formulations has led to controlled and sustained drug release, extended circulation time, enhanced bioavailability, and reduced systemic toxicity, with an overall improvement in drug targeting and therapeutic outcomes in rheumatoid arthritis, psoriasis and other inflammation-based conditions, HIV and Helicobacter pylori infection, and trauma-induced central nervous system secondary degeneration, ultimately opening a door for improved patient compliance due to simplified dosing regimens.