title: Effects of Formulation Variables on the Particle Size and Drug Encapsulation of Imatinib-Loaded Solid Lipid Nanoparticles.
abstract: Imatinib (IMT), an anticancer agent, inhibits receptor tyrosine kinases and is characterized by poor aqueous solubility, extensive first-pass metabolism, and rapid clearance. The aims of the current study are to prepare imatinib-loaded solid lipid nanoparticles (IMT-SLN) and study the effects of associated formulation variables on particle size and drug encapsulation on IMT-SLN using an experimental design. IMT-SLN was optimized by use of a "combo" approach involving Plackett-Burman design (PBD) and Box-Behnken design (BBD). PBD screening resulted in the determination of organic-to-aqueous phase ratio (O/A), drug-to-lipid ratio (D/L), and amount of Tween® 20 (Tw20) as three significant variables for particle size (S z), drug loading (DL), and encapsulation efficiency (EE) of IMT-SLN, which were used for optimization by BBD, yielding an optimized criteria of O/A = 0.04, D/L = 0.03, and Tw20 = 2.50% w/v. The optimized IMT-SLN exhibited monodispersed particles with a size range of 69.0 ± 0.9 nm, ζ-potential of -24.2 ± 1.2 mV, and DL and EE of 2.9 ± 0.1 and 97.6 ± 0.1% w/w, respectively. Results of in vitro release study showed a sustained release pattern, presumably by diffusion and erosion, with a higher release rate at pH 5.0, compared to pH 7.4. In conclusion, use of the combo experimental design approach enabled clear understanding of the effects of various formulation variables on IMT-SLN and aided in the preparation of a system which exhibited desirable physicochemical and release characteristics.
authors: College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyeongsan, 712-749, South Korea.
authors: Biki
authors: B
authors: Gupta
authors: College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyeongsan, 712-749, South Korea.
authors: Bijay Kumar
authors: BK
authors: Poudel
authors: College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyeongsan, 712-749, South Korea.
authors: Shiva
authors: S
authors: Pathak
authors: College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyeongsan, 712-749, South Korea.
authors: Jin Wook
authors: JW
authors: Tak
authors: College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyeongsan, 712-749, South Korea.
authors: Hee Hyun
authors: HH
authors: Lee
authors: College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyeongsan, 712-749, South Korea.
authors: Jee-Heon
authors: JH
authors: Jeong
authors: College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, 55, Hanyangdaehak-ro, Sangnok-gu, Ansan, 426-791, South Korea.
authors: Han-Gon
authors: HG
authors: Choi
authors: College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyeongsan, 712-749, South Korea. csyong@yu.ac.kr.
authors: Chul Soon
authors: CS
authors: Yong
authors: College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyeongsan, 712-749, South Korea. jongohkim@yu.ac.kr.
authors: Jong Oh
authors: JO
authors: Kim
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004339:Drug Compounding / Q000379:methods*; D000068877:Imatinib Mesylate / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D008055:Lipids / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D053758:Nanoparticles / Q000737:chemistry* / Q000378:metabolism; D010316:Particle Size; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D008055:Lipids; D000068877:Imatinib Mesylate
keywords: Box-Behnken design; Plackett-Burman design; imatinib; response surface methodology; solid lipid nanoparticle