International Journal of Nanomedicine (Jul 2023)

Sorafenib-Loaded PLGA Carriers for Enhanced Drug Delivery and Cellular Uptake in Liver Cancer Cells

  • Caputo TM,
  • Cusano AM,
  • Principe S,
  • Cicatiello P,
  • Celetti G,
  • Aliberti A,
  • Micco A,
  • Ruvo M,
  • Tagliamonte M,
  • Ragone C,
  • Minopoli M,
  • Carriero MV,
  • Buonaguro L,
  • Cusano A

Journal volume & issue
Vol. Volume 18
pp. 4121 – 4142

Abstract

Read online

Tania Mariastella Caputo,1,* Angela Maria Cusano,2,* Sofia Principe,1 Paola Cicatiello,1 Giorgia Celetti,1 Anna Aliberti,1 Alberto Micco,2 Menotti Ruvo,3 Maria Tagliamonte,4 Concetta Ragone,4 Michele Minopoli,5 Maria Vincenza Carriero,5 Luigi Buonaguro,4 Andrea Cusano1,2 1Optoelectronics Group, Department of Engineering, University of Sannio, Palazzo Dell’ Aquila Bosco Lucarelli, Benevento, Italy; 2CeRICTscrl Regional Center Information Communication Technology, Palazzo Ex Poste, Benevento, Italy; 3Institute of Biostructure and Bioimaging, National Research Council, Naples, Italy; 4Innovative Immunological Models Unit, Istituto Nazionale Tumori - IRCCS - “Fond G. Pascale”, Naples, Italy; 5Neoplastic Progression Unit, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, Naples, Italy*These authors contributed equally to this workCorrespondence: Andrea Cusano; Anna Aliberti, Palazzo Dell’Aquila Bosco Lucarelli, Corso Garibaldi 107, Benevento, I-82100, Italy, Email [email protected]; [email protected]: Currently, conventional treatments of hepatocellular carcinoma (HCC) are not selective enough for tumor tissue and lead to multidrug resistance and drug toxicity. Although sorafenib (SOR) is the standard first-line systemic therapy approved for the clinical treatment of HCC, its poor aqueous solubility and rapid clearance result in low absorption efficiency and severely limit its use for local treatment.Methods: Herein, we present the synthesis of biodegradable polymeric Poly (D, L-Lactide-co-glycolide) (PLGA) particles loaded with SOR (PS) by emulsion-solvent evaporation process. The particles are carefully characterized focusing on particle size, surface charge, morphology, drug loading content, encapsulation efficiency, in vitro stability, drug release behaviour and tested on HepG2 cells. Additionally, PLGA particles have been coupled on side emitting optical fibers (seOF) integrated in a microfluidic device for light-triggered local release.Results: PS have a size of 248 nm, tunable surface charge and a uniform and spherical shape without aggregation. PS shows encapsulation efficiency of 89.7% and the highest drug loading (8.9%) between the SOR-loaded PLGA formulations. Treating HepG2 cells with PS containing SOR at 7.5 μM their viability is dampened to 40%, 30% and 17% after 48, 129 and 168 hours of incubation, respectively.Conclusion: The high PS stability, their sustained release profile and the rapid cellular uptake corroborate the enhanced cytotoxicity effect on HepG2. With the prospect of developing biomedical tools to control the spatial and temporal release of drugs, we successfully demonstrated the potentiality of seOF for light-triggered local release of the carriers. Our prototypical system paves the way to new devices integrating microfluidics, optical fibers, and advanced carriers capable to deliver minimally invasive locoregional cancer treatments.Graphical Abstract: Keywords: poly(lactic-co-glycolic acid), sorafenib, emulsion solvent evaporation technique, hepatocellular carcinoma, optical fiber, microfluidics

Keywords