2. Academic Validation
  3. Poly(d,l-lactide- co-glycolide) Nanoparticles Encapsulating Doxorubicin for Improved Treatment in Cholangiocarcinoma and Drug-Resistant Cells

Poly(d,l-lactide- co-glycolide) Nanoparticles Encapsulating Doxorubicin for Improved Treatment in Cholangiocarcinoma and Drug-Resistant Cells

  • ACS Appl Bio Mater. 2025 Jul 21;8(7):6055-6065. doi: 10.1021/acsabm.5c00628.
Pornpattra Rattanaseth 1 2,  Kanlaya Katewongsa 3,  Kitti Intuyod 2 4,  Somchai Pinlaor 2 5,  Raynoo Thanan 1 2,  Chadamas Sakonsinsiri 1 2
Affiliations

Affiliations

  • 1 Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
  • 2 Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand.
  • 3 Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
  • 4 Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
  • 5 Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
PMID: 40533874 DOI: 10.1021/acsabm.5c00628
Abstract

Cholangiocarcinoma (CCA), a malignancy of the bile duct epithelium, represents a significant public health issue in the Greater Mekong Subregion, including Thailand. Its aggressive characteristics and late-stage diagnosis lead to poor prognosis and elevated mortality rates. Chemotherapy faces limitations, including the requirement for high and frequent dosages, low cellular uptake, and side effects. To address these challenges, poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) encapsulating doxorubicin (DOX), a chemotherapeutic drug, were developed via a modified nanoprecipitation technique. PLGA was chosen for its biocompatibility and controlled release properties, while the intrinsic fluorescence of DOX allowed cellular uptake monitoring. Among various formulations, Formulation A4 yielded uniform, smooth and spherical NPs with an average diameter of 341 nm, a surface charge of -23 mV, and a suitable encapsulation efficiency. DOX-PLGA NPs were characterized in terms of hydrodynamic diameter (Dh), morphology, heterogeneity of particle sizes, surface charge and surface functional groups, and encapsulation efficiency (EE). Blank NPs, prepared under identical conditions without DOX, were nonhemolytic and biocompatible. The in vitro release profile of the DOX-PLGA NPs showed a biphasic pattern, characterized by both a burst and sustained release, fitting the Korsmeyer-Peppas model. DOX was released more rapidly in an acidic environment compared to physiological pH. DOX-PLGA NPs exhibited greater cytotoxicity relative to free DOX in both KKU-213A and KKU-055 CCA cells, along with increased cellular uptake. In gemcitabine-resistant KKU-213B cells, DOX-PLGA NPs exhibited significantly enhanced cytotoxic effects. The prepared DOX-PLGA NPs demonstrated favorable physicochemical properties, enhanced drug delivery, and improved Anticancer activity, highlighting their potential as an efficient DDS for CCA treatment.

Keywords

Cholangiocarcinoma; Doxorubicin; Drug delivery; Drug resistance; PLGA; Polymeric nanoparticles.

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