Background:Stimuli-responsive drug delivery systems introduced nowadays to enable enhanced drug release upon exogenous stimulus.Research focuses on developing systems for co-administration of drugs to overcome limitat...Background:Stimuli-responsive drug delivery systems introduced nowadays to enable enhanced drug release upon exogenous stimulus.Research focuses on developing systems for co-administration of drugs to overcome limitations of single-drug chemotherapy,such as low response rates,ineffective treatment completion,and drug resistance,leading to aggressive proliferation and recurrence.This research focuses on utilizing the amphiphilic polymer quaternary ammonium palmitoyl glycol chitosan(GCPQ)as a carrier to load hydrophobic curcumin(CUR)and hydrophilic doxorubicin(DOX)to reach the desired target and release the cargo upon exogenous stimuli of ultrasound.Methods:The nanoformulation synthesized using a biocompatible approach,resulting in a stable DOX-CUR-GCPQ nano-formulation upon physicochemical characterization and in vitro analysis using ultrasound.Results:The mean hydrodynamic diameter of DOX-CUR-GCPQ nanomicelles was measured as 95±1.23 nm,PDI 0.32±0.87,zeta potential−35±1.78 mV,and encapsulation efficiency 87.32%±0.3 and 79.42%±0.5 for DOX and CUR respectively.Biocompatibility studies revealed minimal hemolytic activity and biocompatible behavior of the nano-formulation,the co-loaded polymer-based nano-formulation when exposed to Ultrasound at a frequency of 1.5 MHz,for 40 s,on Hep2c cancer cell lines showed a higher release of 89% after 48 h.Moreover,a higher amount of drug internalized within the cells(P<0.0001).Conclusion:The exhibited lower cell viability and IC50(70μg/mL)which demonstrated that ultrasound waves likely facilitated the penetration and uptake of the amphiphilic polymer encapsulating dual drugs into the Hep2c cancer cells,allowing for more efficient delivery of the drugs(DOX and CUR)and broadens the spectrum of anticancer therapy.展开更多
文摘Background:Stimuli-responsive drug delivery systems introduced nowadays to enable enhanced drug release upon exogenous stimulus.Research focuses on developing systems for co-administration of drugs to overcome limitations of single-drug chemotherapy,such as low response rates,ineffective treatment completion,and drug resistance,leading to aggressive proliferation and recurrence.This research focuses on utilizing the amphiphilic polymer quaternary ammonium palmitoyl glycol chitosan(GCPQ)as a carrier to load hydrophobic curcumin(CUR)and hydrophilic doxorubicin(DOX)to reach the desired target and release the cargo upon exogenous stimuli of ultrasound.Methods:The nanoformulation synthesized using a biocompatible approach,resulting in a stable DOX-CUR-GCPQ nano-formulation upon physicochemical characterization and in vitro analysis using ultrasound.Results:The mean hydrodynamic diameter of DOX-CUR-GCPQ nanomicelles was measured as 95±1.23 nm,PDI 0.32±0.87,zeta potential−35±1.78 mV,and encapsulation efficiency 87.32%±0.3 and 79.42%±0.5 for DOX and CUR respectively.Biocompatibility studies revealed minimal hemolytic activity and biocompatible behavior of the nano-formulation,the co-loaded polymer-based nano-formulation when exposed to Ultrasound at a frequency of 1.5 MHz,for 40 s,on Hep2c cancer cell lines showed a higher release of 89% after 48 h.Moreover,a higher amount of drug internalized within the cells(P<0.0001).Conclusion:The exhibited lower cell viability and IC50(70μg/mL)which demonstrated that ultrasound waves likely facilitated the penetration and uptake of the amphiphilic polymer encapsulating dual drugs into the Hep2c cancer cells,allowing for more efficient delivery of the drugs(DOX and CUR)and broadens the spectrum of anticancer therapy.