Advances in the delivery of anticancer drugs by nanoparticles and chitosan-based nanoparticles

Abstract

Cancer is the leading cause of death globally, and conventional treatments have limited efficacy with severe side effects. The use of nanotechnology has the potential to reduce the side effects of drugs by creating efficient and controlled anticancer drug delivery systems. Nanoparticles (NPs) used as drug carriers offer several advantages, including enhanced drug protection, biodistribution, selectivity and, pharmacokinetics. Therefore, this review is devoted to various organic (lipid, polymeric) as well as inorganic nanoparticles based on different building units and providing a wide range of potent anticancer drug delivery systems. Within these nanoparticulate systems, chitosan (CS)-based NPs are discussed with particular emphasis due to the unique properties of CS and its derivatives including non-toxicity, biodegradability, mucoadhesivity, and tunable physico-chemical as well as biological properties allowing their alteration to specifically target cancer cells. In the context of streamlining the nanoparticulate drug delivery systems (DDS), innovative nanoplatform-based cancer therapy pathways involving passive and active targeting as well as stimuli-responsive DDS enhancing overall orthogonality of developed NP-DDS towards the target are included. The most up-to-date information on delivering anti-cancer drugs using modern dosage forms based on various nanoparticulate systems and, specifically, CSNPs, are summarised and evaluated concerning their benefits, limitations, and advanced applications.

Keywords: Anticancer drugs; Chitosan; Chitosan derivatives; Lipid and polymeric nanoparticles; Nanoparticulate drug delivery systems; Organic and inorganic nanoparticles.

Graphical abstract

Fig. 1

Groups of anticancer drugs.

Fig. 2

Schematic diagram of intake and release of chitosan-based nanoparticles for drug delivery. Chitosan-based nanomaterials help transport nanomedicines to tumor tissues for a more extended period. The high-affinity ligand on their surface interacts with tumor markers on cell surfaces, triggering endocytosis. The drug is released inside the cells, killing the tumor cells in acidic, high ROS, and high GSH environments (Tian et al., 2023).

Fig. 3

The stimuli-responsive drug delivery systems.

Fig. 4

Types of NPs used in anticancer drug delivery.

Fig. 5

Different kinds of inorganic-based nano-assembled structures.

Fig. 6

Different kinds of lipid-based nanoplatform structures.

Fig. 7

Different kinds of polymeric nanoparticulate structures.

Fig. 8

Chemical structure of chitosan.

Fig. 9

The properties of CS helpful in medicine and pharmacy.

Fig. 10

Different options for chitosan thiolation.

Fig. 11

The structures of N-CM-chitosan (A), O-CM-chitosan (B), N,O-CM-chitosan (C), N,N-CM-chitosan (D).

Fig. 12

The structures of N,N,N-trimethyl ammonium chitosan (A), N-[(2-hydroxy-3-trimethyl ammonium) propyl] chitosan.

Fig. 13

The structure of glycol chitosan.

Fig. 14

The types of CSNPs designed for anticancer drug delivery.

Fig. 15

Photomicrograph of a lung section showing (A) the histological appearance and architecture of alveolar cells with thin interalveolar septa composed of simple squamous epithelial cells in control mice. (B) Mice treated with urethane showed invasion islands of alveolar adenoma in solid structures. The cells were round with stained cytoplasm, loosely defined cell boundaries, and moderately differentiated squamous cell carcinoma was noticed. (C) Animals that were given urethane displayed alveolar adenomas with a solid pattern, which were demarcated from the surrounding parenchyma. The adjacent alveoli showed collapse and compression. A mass of inflammatory cells infiltrated the lung and caused serious damage. (D) Animals that were given urethane and then treated with BBR showed a partial alleviation of lung structure degradation, along with mild aggregations and areas of inflammatory cellular infiltration in the alveolar spaces. (E) After being administered urethane, animals treated with BBR/CSNPs showed significant improvement in lung structure degradation (Mahmoud et al., 2022).

Fig. 16

Schematic illustration of the final mAb functionalized DOX-loaded PEGylated CSNPs (Helmi et al., 2021).

Fig. 17

Histopathological analysis of skin tumors. a. Untreated tumor b. CS@AgNPs (chitosan-coated silver nanoparticles) treated tumor c. NS*CS@AgNPs (nisin-conjugated chitosan-coated silver nanoparticles) treated tumor d. 5-FU/CS@AgNPs (5-fluorouracil-loaded, chitosan-coated silver nanoparticles) treated tumor e. 5-FU/+NS*CS@AgNPs (5-fluorouracil-loaded and nisin-conjugated chitosan-coated silver nanoparticles) treated tumor (Rana et al., 2022).

Fig. 18

The photograph of tumors from the mice (six reproducibles) excised on day 12 (Saline as a control; DOX; DOX + QUE; DOX/PEG@TMCSNPs (doxorubicin-loaded, polyethylene glycol-coated trimethyl ammonium chitosan nanoparticles); DOX + QUE/PEG@TMCSNPs (doxorubicin and quercetin-loaded, polyethylene glycol-coated trimethyl ammonium chitosan nanoparticles)) (Liu et al., 2021).