Nanocarrier‐Mediated Cytosolic Delivery of Biopharmaceuticals

Abstract

Biopharmaceuticals have emerged to play a vital role in disease treatment and have shown promise in the rapidly expanding pharmaceutical market due to their high specificity and potency. However, the delivery of these biologics is hindered by various physiological barriers, owing primarily to the poor cell membrane permeability, low stability, and increased size of biologic agents. Since many biological drugs are intended to function by interacting with intracellular targets, their delivery to intracellular targets is of high relevance. In this review, the authors summarize and discuss the use of nanocarriers for intracellular delivery of biopharmaceuticals via endosomal escape and, especially, the routes of direct cytosolic delivery by means including the caveolae‐mediated pathway, contact release, intermembrane transfer, membrane fusion, direct translocation, and membrane disruption. Strategies with high potential for translation are highlighted. Finally, the authors conclude with the clinical translation of promising carriers and future perspectives.

Intracellular codelivery of anti-inflammatory drug and anti-miR 155 to treat inflammatory disease

“…However, baicalein is a poorly water-soluble drug, with a molecular weight of 270 g/mol and water-solubility of less than 0.076 mg/mL 16 . On the other hand, anti-miR 155 is a macromolecular drug characterized by high molecular weight, instability and poor membrane penetration 17 , making their codelivery challenging. Furthermore, degradation by the endo-lysosomes is a critical obstacle for intracellular delivery of nucleic acid.…”

Deliver Anti-inflammatory Drug Baicalein to Macrophages by Using a Crystallization Strategy

“…To react to the surrounding situations, macrophages tend to alter their polarization, implying that the polarization may be changed once the drug's simulation disappears (He W. et al, 2019 ). As is well-known, most of drug delivery systems (DDS) release their drugs rapidly in cells after uptake due to the decomposition by the endo-lysosomes (He et al, 2020 ), always discounting the inflammatory activity of drugs. Previous reports indicated that the drug crystals in cells could keep their integrity up to 7–10 h (Lu et al, 2017 ; Qi et al, 2019 ).…”

“…However, its use is always limited due to low solubility in water (Zhang et al, 2009 ). Nanotechnology, such as liposomes, nanoemulsions, polymeric micelles, and nanocrystals, is potent to enhance the solubilization of poorly water-soluble active compounds, along with over 65 products approved for clinical use (Anselmo and Mitragotri, 2016 ; He H. et al, 2019 ; He et al, 2020 ; Yu et al, 2020 ). Of them, nanocrystal technology prepared by formulating drug particles into nanosized particles by top-down or bottom-up approaches is one of the most promising means to solve the solubility (Lu et al, 2019 ), owing to its advantages including its high drug loading, enhanced dissolution rate and saturation solubility, reproducibility of oral absorption, improved dose-bioavailability proportionality, and increased patient compliance (He et al, 2013 , 2016 ; Lv et al, 2018 ; Zhou et al, 2018 ; Zhao et al, 2019 ).…”

Short oligoalanine helical peptides for supramolecular nanopore assembly and protein cytosolic delivery

“…melittin), 65 synthetic (e.g. TP10, Pep-1), 6,63,66 and recent rational strategies, 67,68 the supramolecular control over the folding and assembly of small peptides with low cationic/amphiphilic character has not been sufficiently explored. The work described here introduces the selective non-lytic membrane perturbation from a peptide molecule shorter than a membrane leaflet.…”