Folate-Mediated Targeting and Controlled Release: PLGA-Encapsulated Mesoporous Silica Nanoparticles Delivering Capecitabine to Pancreatic Tumor.

Publisher: ACS Publications Country of Publication: United States NLM ID: 101729147 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2576-6422 (Electronic) Linking ISSN: 25766422 NLM ISO Abbreviation: ACS Appl Bio Mater Subsets: MEDLINE

Original Publication: Washington, DC : ACS Publications, [2018]-

Silicon Dioxide*/chemistry ; Nanoparticles*/chemistry ; Folic Acid*/chemistry ; Polylactic Acid-Polyglycolic Acid Copolymer*/chemistry ; Pancreatic Neoplasms*/drug therapy ; Pancreatic Neoplasms*/pathology ; Pancreatic Neoplasms*/metabolism ; Particle Size* ; Capecitabine*/chemistry ; Capecitabine*/pharmacology ; Drug Screening Assays, Antitumor*; Humans ; Porosity ; Materials Testing ; Cell Proliferation/drug effects ; Biocompatible Materials/chemistry ; Biocompatible Materials/pharmacology ; Biocompatible Materials/chemical synthesis ; Cell Survival/drug effects ; Apoptosis/drug effects ; Delayed-Action Preparations/chemistry ; Drug Liberation ; Cell Line, Tumor ; Drug Carriers/chemistry ; Drug Delivery Systems ; Antimetabolites, Antineoplastic/chemistry ; Antimetabolites, Antineoplastic/pharmacology ; Antimetabolites, Antineoplastic/administration & dosage

The discovery of specifically tailored therapeutic delivery systems has sparked the interest of pharmaceutical researchers considering improved therapeutic effectiveness and fewer adverse effects. The current study concentrates on the design and characterization of PLGA (polylactic-co-glycolic acid) capped mesoporous silica nanoparticles (MSN)-based systems for drug delivery for pH-sensitive controlled drug release in order to achieve a targeted drug release inside the acidic tumor microenvironment. The physicochemical properties of the nanoformulations were analyzed using TEM, zeta potential, AFM, TGA, FTIR, and BET analyses in addition to DLS size. The final formed PLGA-FoA-MSN-CAP and pure MSN had sizes within the therapeutic ranges of 164.5 ± 1.8 and 110.7 ± 2.2, respectively. Morphological characterization (TEM and AFM) and elemental analysis (FTIR and XPS) confirmed the proper capping and tagging of PLGA and folic acid (FoA). The PLGA-coated FoA-MSN exhibited a pH-dependent controlled release of the CAP (capecitabine) drug, showing efficient release at pH 6.8. Furthermore, the in vitro MTT test on PANC1 and MIAPaCa-2 resulted in an IC 50 value of 146.37 μg/ml and 105.90 μg/ml, respectively. Mitochondrial-mediated apoptosis was confirmed from the caspase-3 and annexin V/PI flow cytometry assay, which displayed a cell cycle arrest at the G1 phase. Overall, the results predicted that the designed nanoformulation is a potential therapeutic agent in treating pancreatic cancer.

Keywords: MTT assay; PLGA; capecitabine; mesoporous silica nanoparticles; nanotherapeutics; pH-dependent drug release; pancreatic cancer; tumor microenvironment

7631-86-9 (Silicon Dioxide)
935E97BOY8 (Folic Acid)
1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer)
6804DJ8Z9U (Capecitabine)
0 (Biocompatible Materials)
0 (Delayed-Action Preparations)
0 (Drug Carriers)
0 (Antimetabolites, Antineoplastic)

Date Created: 20240326 Date Completed: 20241216 Latest Revision: 20241216

20250114

10.1021/acsabm.4c00019

38530292