Injectable Thermosensitive Hydrogel Containing Erlotinib‐Loaded Hollow Mesoporous Silica Nanoparticles as a Localized Drug Delivery System for NSCLC Therapy

Abstract

Erlotinib (ERT), oral administration agents, is one of the most pivotal targeted drugs in the treatment of non-small cell lung cancer (NSCLC); however, its poor solubility, low oral bioavailability, and capricious toxicity limit broader clinical applications. In this paper, a novel injectable matrix is prepared based on hollow mesoporous silica nanoparticles (HMSNs) and thermosensitive poly(d,l-lactide)-poly(ethylene glycol)-poly(d,l-lactide) (PDLLA-PEG-PDLLA, PLEL) hydrogel to encapsulate and localize the sustained release of ERT for improved efficacy against NSCLC. The test-tube-inversion method shows that this ERT-loaded hydrogel composite (ERT@HMSNs/gel) presents as an injectable flowing solution under room temperature and transfers into a physically crosslinked non-flowing gel structure at physiological temperature.The ERT@HMSNs/gel composite shows a much longer intratumoral and peritumoral drug retention by in vivo imaging study. Notably, this injectable drug delivery system (DDS) provides an impressive balance between antitumor efficacy and systemic safety in a mice xenograft model. The novel ERT loaded HMSNs/gel system may be a promising candidate for the in situ treatment of NSCLC. Moreover, this study provides a prospective platform for the design and fabrication of a nano-scaled delivery system for localized anticancer therapies.

pH/Thermo-Responsive Grafted Alginate-Based SiO2 Hybrid Nanocarrier/Hydrogel Drug Delivery Systems

“…Nanocarriers loaded with payloads encapsulated within an injectable hydrogel constitute another strategy to design controlled sustainable DDS [ 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 ]. One of the benefits of this strategy is that the nanocarriers are retained in the targeting point and release the therapeutics sustainably, due to the very high viscosity exhibited within the hydrogel environment.…”

Nanotechnology-based drug delivery systems in orthopedics

“…Compared to traditional drugs, nanotechnology-based drug delivery systems have several advantages, including high surface area-to-volume ratio for efficient drug loading, improved targeting due to their small size allowing them to overcome biological barriers, enhanced drug solubility and physical stability in biological media, ease of surface functionalization to sense, image, diagnose and deliver pharmaceuticals by the conjugation of biological targeting moieties, controlled dissolution rates/drug bioavailability, reduced adverse side effects, and size similarity to interact with, and modulate biological component. [20][21][22] Various nanotechnology-based drug delivery vehicles, including polymeric nanoparticles, lipid nanoparticles, dendrimers, quantum dots, carbon nanotubes, and metallic nanoparticles have brought great advancements in the field of drug delivery, as well as the entire medical field. [23][24][25][26][27] These delivery strategies have been applied for the treatment of bone-related diseases for increasing treatment efficiency and specificity of conventional clinical therapies.…”

m6A demethylase FTO induces NELL2 expression by inhibiting E2F1 m6A modification leading to metastasis of non-small cell lung cancer

“… 1 Among lung cancer subtypes, non-small cell lung cancer (NSCLC) accounts for more than 80 percent of all lung malignancy. 2 E2F transcription factor-1 (E2F1) is a key transcriptional factor that has been highlighted for participating in a series of biological processes including cell proliferation and apoptosis, 3 oxidative metabolism, 4 and cellular senescence. 5 Notably, recent studies have pointed out the involvement of E2F1 activation in hepatocarcinogenesis, the progression of hepatocellular carcinoma, and also the brain metastasis of lung adenocarcinoma.…”