Regulation of particle morphology of pH-dependent poly(epsilon-caprolactone)-poly(gamma-glutamic acid) micellar nanoparticles to combat breast cancer cells.
The advantage of polymeric drug carriers lies in the uptake of the polymer nanoparticles by cancer cells before they release the drug, thereby reducing its toxic effects on healthy cells. A poly(gamma-glutamic acid)-b-poly(epsilon-caprolactone)-b-poly(gamma-glutamic acid) block copolymer was synthesized to encapsulate the anti-cancer drug doxorubicin in the treatment of wild type human breast cancer cells (MCF-7/WT). This pH-controllable carrier is negatively-charged in the presence of healthy tissues leading to lower cellular uptake. On the other hand, it becomes more hydrophobic in the acidic environment of cancer tissues, increasing its cellular uptake through the lipid bilayer. The block copolymer was characterized using Fourier transform infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, differential scanning calorimetry and dynamic light scattering. The micelles formed at a critical concentration range of 62-130 microg/mL depending on the composition of poly(gamma-glutamic acid) and poly(epsilon-caprolactone) chains. The nano-sized micelles were found to have pH-dependent sizes in the range of 90-200 nm. The role of poly(gamma-glutamic acid) was to increase the hydrophilicity and decrease the particle size of the copolymer. The structures of micelles that were more compact and less anionic showed better stability in plasma. It was found that the drug loading content and drug loading efficiency were 12.14% and 97.22% respectively. The copolymer showed shrinking and aggregation at low pH which led to a slower drug release. These nano-sized micelles showed potential as effective drug delivery carriers for doxorubicin because of its accumulation and slow release inside the MCF-7/WT cells.
Department of Biomedical Engineering and R&D Center for Biomedical Microdevice Technology, Chung Yuan Christian University, Chung Li, Taiwan 32023, ROC.
Ann Shireen
AS
Chan
Chao-Hsuan
CH
Chen
Chun-Ming
CM
Huang
Ming-Fa
MF
Hsieh
D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D004355:Drug Stability; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008823:Micelles; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010316:Particle Size; D011091:Polyesters / Q000008:administration & dosage / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D011099:Polyglutamic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D011817:Rabbits; D017550:Spectroscopy, Fourier Transform Infrared
D004337:Drug Carriers; D008823:Micelles; D011091:Polyesters; C511775:poly(gamma-glutamic acid); C016240:polycaprolactone; D011099:Polyglutamic Acid; D011092:Polyethylene Glycols; D004317:Doxorubicin