Dual-drug-loaded lipid-based formulation for colon cancer therapeutics: in vitro optimization and characterization
Abstract Objective The current investigation aims to fabricate, optimize and characterize dual-drug-loaded liposomes for the management of colon cancer. Significance Lipid-based nanocarriers are versatile nanocarriers that facilitate the loading of both hydrophilic and hydrophobic therapeutic agents. The simultaneous delivery of capecitabine (CAP) and celecoxib (CEL) is anticipated to enhance anticancer efficacy against colon cancer. Methods CAP-CEL-loaded liposomes (CAP-CEL-LIPs) were designed and optimized utilizing Box–Behnken Design (BBD). The optimized LIPs were characterized for particle size, polydispersity index (PDI), entrapment efficiency and morphological studies. In vitro drug release studies were conducted under both acidic and physiological conditions. Hemocompatibility was evaluated using the hemolysis assay and the stability of the LIPs was assessed over a duration of one month. Results The optimized CAP-CEL-LIPs demonstrated a mean particle size of 130 ± 2.36 nm with a PDI of 0.162 ± 0.008, showing the homogeneous particle size distribution. The encapsulation efficiency for CAP and CEL was found to be 64.96 ± 2.81% and 92.23 ± 2.22%, respectively. SEM and TEM images revealed the spherical morphology of the developed LIPs. In vitro drug release investigations revealed a controlled release profile for both drugs under both acidic and physiological conditions. The hemolysis assay showed hemolysis rate of less than 2%, thereby confirming superior blood compatibility. Stability data indicated that LIPs remained stable for one-month. The developed CAP-CEL-LIPs showed significant cytotoxic potential with enhanced cellular uptake and apoptotic activity against colon cancer cells. Conclusion The engineered CAP-CEL-LIPs could be a promising platform for managing colon cancer. GRAPHICAL ABSTRACTFlowchart and graphs illustrating preparation of dual-drug liposomes and their characterization for colon cancer treatment.The figure is organized into two sections. The top section shows the flowchart for preparing dual-drug liposomes with capecitabine and celecoxib, detailing processes using a rotary evaporator, leading to CAP-CEL liposome formation and their anticancer effects following parenteral administration. The bottom section displays characterization graphs, including a 3D plot of design space, particle size distribution with a peak around 100 nm, zeta potential graphs, SEM images showing liposome structure, bar charts for %EE (encapsulation efficiency) and %DL (drug loading), along with cumulative drug release over time, DSC thermograms, and %hemolysis analysis.