@article {Fatouh20221161,
	title = {Liver targeting of ledipasvir via galactosylated chitosan{\textendash}coated spanlastics: chemical synthesis, statistical optimization, in vitro, and pharmacokinetic evaluation},
	journal = {Drug Delivery and Translational Research},
	volume = {12},
	number = {5},
	year = {2022},
	note = {<p>Cited by: 2</p>
},
	pages = {1161 {\textendash} 1174},
	publisher = {Springer},
	type = {Article},
	abstract = {<p>Introduction: Ledipasvir is an effective direct acting antiviral agent used in the treatment of hepatitis C virus. The high price of ledipasvir was a reason for its limited provision to wide population of HCV patients. Objectives: Our objective is the formulation of liver targeted drug delivery system that can increase the amount of ledipasvir delivered to liver and prolong its liver residence in an attempt to reduce its recommended dose and its costing in the treatment of HCV. Methods: Different ledipasvir-loaded spanlastic formulations were prepared using the ethanol injection method and evaluated with respect to the particle size, zeta potential, polydispersity index, and entrapment efficiency \%. Using Design-Expert {\textregistered} software, the optimum spanlastics formulation was selected; then, it was coated by synthesized galactosylated chitosan. A pharmacokinetic study was carried out to evaluate the ability of the prepared galactosylated chitosan-coated spanlastics formulation to enhance ledipasvir liver bioavailability when it was administrated via the oral route. Results: The pharmacokinetic study revealed that the optimized galactosylated chitosan{\textendash}coated spanlastics exhibited significantly higher liver peak concentration (Cmax) and area under liver concentration versus time curve (AUC0{\textendash}72 h) and significant prolongation in the liver terminal half life (t{\textonehalf}) and mean residence time (MRT) compared to the free ledipasvir dispersion with values of 6270 ng/g, 61,706.3 ng.h/g, 15.85 h, and 24.66 h, respectively. Conclusions: Enhanced liver bioavailability of ledipasvir has been accomplished using the developed galactosylated chitosan{\textendash}coated spanlastics which can be a base for probable reduction in the required dose of ledipasvir in HCV treatment. Graphical abstract: [Figure not available: see fulltext.] {\textcopyright} 2021, Controlled Release Society.</p>
},
	doi = {10.1007/s13346-021-00993-8},
	url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85105892572\&doi=10.1007\%2fs13346-021-00993-8\&partnerID=40\&md5=606ed51101959b0b2b82596eb77787b1},
	author = {Fatouh, Ahmed M. and Ahmed H. Elshafeey and Ahmed Abd Elbary}
}
