Optimization of epirubicin nanoparticles using experimental design for enhanced intravesical drug delivery.
The aim of this study was to develop poly(ethyl-2-cyanoacrylate) (PECA) epirubicin-loaded nanoparticles (EPI-NP). A 2(3) factorial design was adopted with the type of surfactant, surfactant concentration and the pH of the polymerization medium as independent variables. The particle size, entrapment efficacy and polydispersity index of eight formulations were then evaluated. Two optimal EPI-NP formulations, 2% Tween 80 EPI-NP (TW80 EPI-NP) and 0.5% pluronic F68 EPI-NP (F68 EPI-NP) at pH 2.5 were developed. The sizes of TW80 EPI-NP and F68 EPI-NP at maximum intensity were 90 and 220 nm, respectively. Both TW80 EPI-NP and F68 EPI-NP showed potent cytotoxicity against human bladder cancer T24 and RT4 cells, compared with aqueous solutions of epirubicin (EPI-AQ). The penetration and accumulation of EPI-NPs in pig urothelium were studied by tissue concentration-depth profiles and fluorescence microscopy. The cumulative amounts of epirubicin following EPI-AQ, TW80 EPI-NP and F68 EPI-NP treatments were 842.48+/-24.66, 1314.66+/-33.07 and 595.21+/-24.16 microg, respectively. The current study showed the successful development of urothelium adhesive and penetrative PECA EPI-NPs. This has potential for the in vivo application of epirubicin-loaded nanoparticles for intravesical instillation in bladder cancer therapy.
Chang
Li-Ching
LC
Department of Occupational Therapy, I-Shou University, Kaohsiung, Taiwan.
Wu
Shu-Chin
SC
Tsai
Jen-Wei
JW
Yu
Tsan-Jung
TJ
Tsai
Tong-Rong
TR
D000283:Administration, Intravesical; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003487:Cyanoacrylates / Q000737:chemistry; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000379:methods*; D015251:Epirubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D012107:Research Design; D013501:Surface-Active Agents / Q000737:chemistry; D019459:Urothelium / Q000187:drug effects
D000903:Antibiotics, Antineoplastic; D003487:Cyanoacrylates; D004337:Drug Carriers; D013501:Surface-Active Agents; D015251:Epirubicin