Nanotechnology for efficient drug loading and delivery: A comprehensive review of nanocarriers, loading strategies, therapeutic applications, and translational challenges

Abstract

Nanotechnology has revolutionized pharmaceutics by enabling the entrapment of bioactive molecules in carriers that enhance their aqueous solubility, chemical stability, pharmacokinetics and tissue-specificity. Nanocarrier-based delivery system can entrap small molecules, peptides, proteins, nucleic acids and imaging probes with the additional benefits of controlled release and diminished systemic toxicity. This updated review covers high efficiency loading and delivery of drugs with focus on the impact of the nanocarrier structure and physicochemical characteristics, formulation processing, biological interaction and manufacturing approach on drug encapsulation efficiency, loading capacity, drug retention, drug release, and therapeutic effect [1-4],[9-18]. Several classes of nanocarriers: liposomes, lipid nanoparticles (LNPs), polymeric nanoparticles, polymeric micelles, dendrimers, mesoporous silica nanoparticles, inorganic nanoparticles, nanogels and exosome-like systems are discussed and compared in relation to their structure, loading mechanisms, advantages and limitations [18-21]. Emphasis on passive loading, active/remote loading, microfluidic production, flash nanoprecipitation, protein corona formation, passive/active targeting, stimuli-responsive release, characterization, and medically approved nanomedicines is provided [22-28,51-58]. Lastly, translation bottlenecks such as poor in vivo delivery efficiency, scale-up, sterilization, regulatory requirements, and long-term safety, are critically discussed along with potential solutions including biomimetic design, in silico prediction, artificial intelligence-guided formulation, quality-by-design manufacturing [8,9,24],[27-30],[59,60].