A Tri-Stimuli Responsive (Maghemite/PLGA)/Chitosan Nanostructure with Promising Applications in Lung Cancer

Abstract

A (core/shell)/shell nanostructure (production performance ≈ 50%, mean diameter ≈ 330 nm) was built using maghemite, PLGA, and chitosan. An extensive characterization proved the complete inclusion of the maghemite nuclei into the PLGA matrix (by nanoprecipitation solvent evaporation) and the disposition of the chitosan shell onto the nanocomposite (by coacervation). Short-term stability and the adequate magnetism of the nanocomposites were demonstrated by size and electrokinetic determinations, and by defining the first magnetization curve and the responsiveness of the colloid to a permanent magnet, respectively. Safety of the nanoparticles was postulated when considering the results from blood compatibility studies, and toxicity assays against human colonic CCD-18 fibroblasts and colon carcinoma T-84 cells. Cisplatin incorporation to the PLGA matrix generated appropriate loading values (≈15%), and a dual pH- and heat (hyperthermia)-responsive drug release behaviour (≈4.7-fold faster release at pH 5.0 and 45 °C compared to pH 7.4 and 37 °C). The half maximal inhibitory concentration of the cisplatin-loaded nanoparticles against human lung adenocarcinoma A-549 cells was ≈1.6-fold less than that of the free chemotherapeutic. Such a biocompatible and tri-stimuli responsive (maghemite/PLGA)/chitosan nanostructure may found a promising use for the effective treatment of lung cancer.

Recent Advances in the Surface Functionalization of PLGA-Based Nanomedicines

“…Therefore, CS-coated PLGA nanosystems can increase biocompatibility, protect from opsonization and improve retention and cellular uptake [ 98 , 99 ]. Additionally, CS coating has been used as a strategy to achieve sustained and pH-responsive drug release from PLGA nanostructures [ 100 , 101 , 102 ].…”

Chitosan‐based nanoscale systems for doxorubicin delivery: Exploring biomedical application in cancer therapy

“…Furthermore, it can be used in treatment of infectious diseases such as COVID‐19 that is inflicting nowadays. 55 , 56 , 57 , 58 , 59 , 60 The CS‐based nanostructures have demonstrated great efficacy in prolonged delivery of drugs 61 , 62 that is of utmost importance in cancer therapy. Due to CS's positive charge, it can easily form complexes with negatively charged nucleic acids.…”

“…Notably, CS‐based nano‐scale delivery systems for pulmonary delivery are of importance in treatment of related cancers such as lung tumor. Furthermore, it can be used in treatment of infectious diseases such as COVID‐19 that is inflicting nowadays 55–60 . The CS‐based nanostructures have demonstrated great efficacy in prolonged delivery of drugs 61,62 that is of utmost importance in cancer therapy.…”

Pilot-scale co-precipitation synthesis of a novel active ingredient made of ultrasmall iron (oxyhydr)oxide nanoparticles for the treatment of hyperphosphatemia

“…16 Thus, the synthesis procedures following the co-precipitation route are typically described in research studies with small volumes of up to 1 L and a small amount of product. 11,[17][18][19][20] The largest reported co-precipitation process syntheses are in the range up to 1.2 L total volume and 5.4 g L −1 of product. 21,22 To our knowledge, no study has reported a transfer from the laboratory to larger scales and the challenges associated with the scale-up yet.…”

“…16 Thus, the synthesis procedures following the co-precipitation route are typically described in research studies with small volumes of up to 1 L and a small amount of product. 11,17–20 The largest reported co-precipitation process syntheses are in the range up to 1.2 L total volume and 5.4 g L −1 of product. 21,22…”