Strategies for the enhanced intracellular delivery of nanomaterials

Abstract

The intracellular delivery of nanomaterials and drugs has been attracting increasing research interest, mainly because of their important effects and functions in several organelles. Targeting specific organelles can help treat or decrease the symptoms of diabetes, cancer, infectious, and autoimmune diseases. Tuning biological and chemical properties enables the creation of functionalized nanomaterials with enhanced intracellular uptake, ability to escape premature lysosome degradation, and to reach a specific target. Here, we provide an update of recent advances in the intracellular delivery mechanisms that could help drugs reach their target more efficiently.

<p>Improvements in the Oral Absorption and Anticancer Efficacy of an Oxaliplatin-Loaded Solid Formulation: Pharmacokinetic Properties in Rats and Nonhuman Primates and the Effects of Oral Metronomic Dosing on Colorectal Cancer</p>

“…During this process, ODSF that entered through endocytosis or macropinocytosis can be internalized via formation of early or late endosomes, caveosomes, or macropinosomes; it can then be delivered to lysosomes or cytoplasm, or may exit enterocytes via the endoplasmic reticulum (ER) or ER/Golgi apparatus pathway. 71 – 73 Moreover, effective lysosomal and cytoplasmic escape of ODSF is necessary to achieve optimum intracellular density and oral bioavailability to elicit an adequate pharmacological response. Therefore, to confirm exocytosis and involvement of the ER-to-Golgi apparatus pathway in the intracellular trafficking of ODSF micelles, the effects of brefeldin A, a specific inhibitor of the ER/Golgi secretory pathway, were examined.…”

“…Abbreviations: OP, oxaliplatin; DLM, N α -deoxycholyl-L-lysyl-methylester; OP/DLM, ion-pairing complex between OP and DLM; P188, poloxamer 188; ODSF, solid oral formulation of OP/DLM with P188 and Labrasol; P-gp, P-glycoprotein; EGTA, ethylene glycol-bis-(2-aminoethyl ether)-N,N,N´,N´-tetraacetic acid; P app , apparent permeability of ODSF across a Caco-2 cell monolayer; A to B, transport from apical to basal region; B to A, transport from basal to apical region; Act D, actinomycin D; CFZ, clofazimine; OST α/β , organic solute transporter alpha/beta; MBCD, methyl-β-cyclodextrin; Cys A, cyclosporine A. caveosomes, or macropinosomes; it can then be delivered to lysosomes or cytoplasm, or may exit enterocytes via the endoplasmic reticulum (ER) or ER/Golgi apparatus pathway. [71][72][73] Moreover, effective lysosomal and cytoplasmic escape of ODSF is necessary to achieve optimum intracellular density and oral bioavailability to elicit an adequate pharmacological response. Therefore, to confirm exocytosis and involvement of the ER-to-Golgi apparatus pathway in the intracellular trafficking of ODSF micelles, the effects of brefeldin A, a specific inhibitor of the ER/ Golgi secretory pathway, were examined.…”

Following the Fate of Dye-Containing Liposomes In Vitro

“…There are various means to approach the challenges, from in vitro conditions to more complex in vivo studies. Recently, the intracellular delivery of nanomaterials as well as nanomaterial-associated drugs have attracted increasing attention due to the ever growing interest in subcellular drug targeting [19]. To be able to confirm the intracellular fate of nanoparticles, and optimize their properties to achieve subcellular delivery, we aimed to focus on a rather simple yet often neglected interplay between the nanocarrier and the dye used to follow its fate.…”

Impact of CEA-targeting Nanoparticles for Drug Delivery in Colorectal Cancer

“…Drug nanocarriers are solid and colloidal particles that emerge as safe drug vehicles, designed to generate many fewer toxic side effects and deliver high quantities of cargo to a very specific site of interest (Richards et al, 2017). Nanoparticles can be 1-1000 nm in diameter (Azevedo et al, 2018); however, those less than 200 nm are most suited for intravenous administrations, considering the width of the body's microcapillaries. Their advantages over microparticles (with a diameter .1 mm) are notable; when the diameter of capillaries is 5-6 mm, particles over 5 mm could aggregate and drive an embolism (Singh and Lillard, 2009).…”