Nanovehicular Intracellular Delivery Systems

Abstract

This article provides an overview of principles and barriers relevant to intracellular drug and gene transport, accumulation and retention (collectively called as drug delivery) by means of nanovehicles (NV). The aim is to deliver a cargo to a particular intracellular site, if possible, to exert a local action. Some of the principles discussed in this article apply to noncolloidal drugs that are not permeable to the plasma membrane or to the blood–brain barrier. NV are defined as a wide range of nanosized particles leading to colloidal objects which are capable of entering cells and tissues and delivering a cargo intracelullarly. Different localization and targeting means are discussed. Limited discussion on pharmacokinetics and pharmacodynamics is also presented. NVs are contrasted to micro-delivery and current nanotechnologies which are already in commercial use. Newer developments in NV technologies are outlined and future applications are stressed. We also briefly review the existing modeling tools and approaches to quantitatively describe the behavior of targeted NV within the vascular and tumor compartments, an area of particular importance. While we list “elementary” phenomena related to different level of complexity of delivery to cancer, we also stress importance of multi-scale modeling and bottom-up systems biology approach.

Slow‐Release Formulation of Cowpea Mosaic Virus for In Situ Vaccine Delivery to Treat Ovarian Cancer

“…Even at the highest salt concentration measured however, CPMV‐G4 aggregates would still be too large to passively diffuse across blood vessels to enter systemic circulation from the intraperitoneal space (size limit < 100 nm) and would require disassembly or lymphatic drainage for eventual clearance 30. Further, the slow time course of disassembly of the aggregates at physiological salt concentrations (Figure 1C), makes this assembly a promising candidate for continued presence in the IP space with slow release over time.…”

PLGA-Based Nanoparticles as Cancer Drug Delivery Systems

“…Depending on the molecular weight copolymer ratio, the degradation time can vary since several months to and several years. (Vert et al, 1994;Prokop and Davidson, 2008;Danhier et al, 2012). Lactic acid is more hydrophobic than glycolic acid and, thus, lactide-rich PLGA copolymers are less hydrophilic, absorb less water, and consequently, degrade more gradually (Park, 1994;Schliecker et al, 2003;Dinarvand et al, 2011).…”

Controlled release and intracellular protein delivery from mesoporous silica nanoparticles

“…SBA-15 materials are characterized by larger pore sizes (5-30 nm), allowing them to accommodate and deliver large, therapeutic molecules [32]. However, the particle sizes of SBA-15 are generally in the range of 800 nm to 2 µm, and small particle size (<200 nm) is required for efficient cellular uptake [11,12]. These large particle sizes lead to some limitations of SBA-15, namely, large molecular diffusion and adsorption capacity.…”

“…Once it escapes, it travels through the cytoplasm where the proteins are released from the vehicle to interact with its specific target [3,4,[6][7][8][9][10][11]. One type of inorganic nanoparticle that has been successfully applied as a controlled-release drug delivery system for intracellular protein delivery is mesoporous silica nanoparticle (MSN) materials [4,12].…”