Conventional and Functionalised Nanostructured Lipid Carriers for Pulmonary-Targeted Delivery Systems

Pulmonary delivery systems are potential routes for numerous lung-related disease treatments. The pulmonary delivery system can be utilised for local deposition and systemic application due to its large surface area and high vascularisation within the alveolar epithelium. This can lead to high permeability and bioavailability of drugs. This review explores the utilisation of conventional nanostructured lipid carriers in pulmonary delivery system applications. Due to their high entrapment efficiency, stability, and biocompatibility, nanostructured lipid carriers can be used as drug carriers through the pulmonary delivery system. Using nanostructured lipid carriers can enhance drug deposition into deeper lungs, improve bioavailability and efficacy, provide sustained and controlled release profiles of drugs, enhance antimicrobial activity, enhance cellular uptake and penetration, and improve bioavailability. However, conventional nanostructured lipid carriers have a major drawback: low selectivity in target cells. The non-selective properties of these carriers can lead to potential side effects, high toxicity, and reduced effectiveness. Therefore, recent applications of functionalised nanostructured lipid carriers have been evaluated through in vitro and in vivo studies to prove their safety and effectiveness in pulmonary-targeted delivery. Nanostructured lipid carriers have been functionalised to improve their selectivity and effectiveness. This review discusses various functionalised nanostructured lipid carriers through surface modification and their mechanism, including hydrophilic polymers, polysaccharides, peptides and proteins, small molecules, surfactants, genes, antibodies, and pH-sensitive polymers. Furthermore, key case studies in clinical translation are examined to illustrate the practical applications and progress of these advanced nanocarriers. This review also discusses the potential challenges in development, including pulmonary-specific targeting, toxicity, and immunogenicity concerns, as well as production and scalability challenges. Moreover, developing functionalised nanocarriers presents new opportunities by highlighting effective strategies to address existing challenges and accelerate their progression from experimental research to clinical translation.