Advances in Drug Targeting, Drug Delivery, and Nanotechnology Applications: Therapeutic Significance in Cancer Treatment

Abstract

In the 21st century, thanks to advances in biotechnology and developing pharmaceutical technology, significant progress is being made in effective drug design. Drug targeting aims to ensure that the drug acts only in the pathological area; it is defined as the ability to accumulate selectively and quantitatively in the target tissue or organ, regardless of the chemical structure of the active drug substance and the method of administration. With drug targeting, conventional, biotechnological and gene-derived drugs target the body's organs, tissues, and cells that can be selectively transported to specific regions. These systems serve as drug carriers and regulate the timing of release. Despite having many advantageous features, these systems have limitations in thoroughly treating complex diseases such as cancer. Therefore, combining these systems with nanoparticle technologies is imperative to treat cancer at both local and systemic levels effectively. The nanocarrier-based drug delivery method involves encapsulating target-specific drug molecules into polymeric or vesicular systems. Various drug delivery systems (DDS) were investigated and discussed in this review article. The first part discussed active and passive delivery systems, hydrogels, thermoplastics, microdevices and transdermal-based drug delivery systems. The second part discussed drug carrier systems in nanobiotechnology (carbon nanotubes, nanoparticles, coated, pegylated, solid lipid nanoparticles and smart polymeric nanogels). In the third part, drug targeting advantages were discussed, and finally, market research of commercial drugs used in cancer nanotechnological approaches was included.

Keywords: drug carriers; drug delivery systems; drug targeting; nanotechnology.

Figure 2

(A) 3D bioprinted breast tumor-stroma tumor models Reproduced with permission from [93], Elsevier, 2023. (B) naproxen-loaded thermoplastic polymer drug delivery system with electrospinning method Reproduced with permission from [102], Elsevier, 2016. (C) the antitumor effect of Dox combined with OPE and NR in vivo (xenograft tumor mouse model) Reproduced from [112], Elsevier, 2020. (D) zebrafish xenograft model Reproduced from [113], ACS publication, 2016 (E) schematic illustration of the 3D-printed microcontainers (Eudragit L100 and furosemide) that were appropriate as drug carriers Reproduced with permission from [114], Wiley Online library, 2023. (F) graphical abstract of transdermal patches embedded in nanostructured lipid carriers (NLCs) to improve transdermal delivery of capsaicin Reproduced with permission from [115], Elsevier, 2022. (G) in the in vivo wound model and in vivo persistence and histology images of resveratrol-loaded transdermal biomembrane Reproduced with permission from [116], Elsevier, 2023.

Figure 3

(A) The sonochemical method was used to prepare starch/MWCNT-Gl NCs nanoparticles for drug delivery Reproduced with permission from [166], Elsevier, 2018. (B) Arthritis imaging of HiPco-cy5.5 in the control group and mice with highlighted arthritis and normal joint Reproduced [167], MDPI, 2021. (C) Oleic acid-conjugated chitosan (oleyl-chitosan) is a powerful platform for encapsulating oleic acid-decorated iron oxide nanoparticles (ION) Reproduced with permission from [178], ACS Publications, 2018. (D) Graphical abstract of PEG-coated Zein nanoparticles Reproduced [183], Elsevier, 2021. (E) Graphical abstract of DOX/Zr-UİO-66-PEG-F3 Reproduced with permission from [184], ACS Publications, 2021. (F) DOX-loaded phosphorylcholine-based zwitterionic polymer nanogels’ charge-conversion ability at tumor extracellular pH Reproduced with permission from [201], Elsevier, 2019. (G) Schematic illustration of the poly(phosphorylcholine)-based (HPMPC) nanogel with long blood circulation, blood-brain barrier (BBB) penetration, and hypoxic controlled drug release for glioblastoma drug delivery Reproduced with permission from [202], Elsevier, 2021. (H) Trastuzumab-dendrimer-fluorine drug delivery system’s efficacy can be evaluated in 3D breast cell culture Reproduced from [203], Elsevier, 2021. (I) Bis-MPA dendrimers and related structures Reproduced with permission from [204], Elsevier, 2012.

Figure 5

(A) Cellular and signaling components of the blood–brain barrier (BBB) in activated EphA and EphB receptors and endothelial cell (EC) junctions (TJ) Reproduced from [232], Frontiers, 2018. (B) various crossing mechanisms at the blood brain–barrier Reproduced with permission from [235], Wolters Kluwer, 2004. (C) histology of rats with intracranially implanted 101/8 glioblastoma Reproduced with permission from [244], Wiley Online Library, 2004. (D) graphical abstract of anti-VEGF antibody-derived drugs Reproduced from [245], MDPI, 2023. (E) mechanisms of the action of T-DM1 Reproduced from [243], Frontiers, 2023.

Figure 1

(A) Drug delivery with active targeting on a cancer cell, crosslinking mechanisms. (B) Thermo condensation, (C) Self-assembly, (D) Ionic gelation, (E) Electrostatic interaction, (F) Chemical crosslinking, (G) Various surface-engineered poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) for passive or active tumor targeting. Arg-Gly-Asp (RGD); reticuloendothelial system (RES); transferrin (Tf); vascular endothelial growth factor (VEGF) Reproduced from [71], MDPI, 2019. (H) Graphical abstract of enhanced permeability and retention (EPR) Reproduced from [72], MDPI, 2022.

Figure 4

Schematic representation of surface properties, ligand and receptor targeting, and size characteristics of blood brain barrier penetration. “During the preparation of this manuscript, the author(s) used [Napkin AI, beta-0.10.2] for the purposes of [drawing figure]. The authors have reviewed and edited the output and take full responsibility for the content of this publication”.