Surface Modification of Solid Lipid Nanoparticles: Enhancements in DrugDelivery and Treatment Efficacy

Abstract: Solid lipid nanoparticles (SLNs) have surfaced as promising nanocarriers in drug delivery systems due to their remarkable biocompatibility, high drug encapsulation efficiency, and capability to protect therapeutic agents from chemical and enzymatic degradation. Despite their promising potential, nanoparticles continue to face significant challenges related to biological barriers and biodistribution, which restrict their efficacy in clinical applications. One of the primary issues with traditional SLNs is their poor targeting capacity and rapid clearance by the reticuloendothelial system, which limits their effectiveness in drug delivery. In addition, their low bioavailability poses a major drawback, potentially leading to reduced therapeutic efficacy and an increased risk of side effects. Other challenges include limited drug-loading capacity, particle instability, potential immunogenicity, and the high cost of production, all of which hinder their widespread application in clinical treatments. To address these limitations, advanced techniques and chemical strategies have been employed to modify and functionalize the nanoparticle surfaces, optimizing their biological interactions and enhancing their therapeutic efficacy. Among these strategies, the use of polymers such as polyethylene glycol and chitosan, as well as functional lipids, has been extensively explored for improving the stability, mass transport, targeting, and circulation time of SLNs while minimizing immune detection. In addition, the potential of advanced modifications, such as cysteine-functionalized SLNs and ion pairing, to further optimize drug release and targeting is discussed. This review underscores how these tailored surface modifications can address existing challenges, paving the way for SLNs to emerge as highly effective drug delivery systems in clinical settings. The review explores how these alterations impact the therapeutic efficiency and pharmacokinetics of SLNs. With further optimization, surface-modified SLNs hold promise as an efficient and targeted drug delivery system for a variety of medical applications.