title: Factorial Design Based Multivariate Modeling and Optimization of Tunable Bioresponsive Arginine Grafted Poly(cystaminebis(acrylamide)-diaminohexane) Polymeric Matrix Based Nanocarriers.
abstract: Desired characteristics of nanocarriers are crucial to explore its therapeutic potential. This investigation aimed to develop tunable bioresponsive newly synthesized unique arginine grafted poly(cystaminebis(acrylamide)-diaminohexane) [ABP] polymeric matrix based nanocarriers by using L9 Taguchi factorial design, desirability function, and multivariate method. The selected formulation and process parameters were ABP concentration, acetone concentration, the volume ratio of acetone to ABP solution, and drug concentration. The measured nanocarrier characteristics were particle size, polydispersity index, zeta potential, and percentage drug loading. Experimental validation of nanocarrier characteristics computed from initially developed predictive model showed nonsignificant differences (p > 0.05). The multivariate modeling based optimized cationic nanocarrier formulation of <100 nm loaded with hydrophilic acetaminophen was readapted for a hydrophobic etoposide loading without significant changes (p > 0.05) except for improved loading percentage. This is the first study focusing on ABP polymeric matrix based nanocarrier development. Nanocarrier particle size was stable in PBS 7.4 for 48 h. The increase of zeta potential at lower pH 6.4, compared to the physiological pH, showed possible endosomal escape capability. The glutathione triggered release at the physiological conditions indicated the competence of cytosolic targeting delivery of the loaded drug from bioresponsive nanocarriers. In conclusion, this unique systematic approach provides rational evaluation and prediction of a tunable bioresponsive ABP based matrix nanocarrier, which was built on selected limited number of smart experimentation.
authors.affiliation: Translational Drug and Gene Delivery Research (TransDGDR) Laboratory, Department of Pharmaceutical Sciences, Department of Pharmaceutics and Drug Delivery, Research of Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi , University, Mississippi 38677, United States.|Translational Drug Delivery Research (TransDDR) Laboratory, Department of Pharmaceutical Sciences, The Daniel K. Inouye College of Pharmacy, University of Hawai'i at Hilo , Hilo, Hawaii 96720, United States.
authors.forename: Rongbing
authors.initials: R
authors.lastname: Yang
authors.affiliation: Center for Controlled Chemical Delivery (CCCD), Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah , Salt Lake City, Utah 84112, United States.|School of Dentistry, University of Utah , Salt Lake City, Utah 84112, United States.
authors.forename: Kihoon
authors.initials: K
authors.lastname: Nam
authors.affiliation: Center for Controlled Chemical Delivery (CCCD), Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah , Salt Lake City, Utah 84112, United States.
authors.forename: Sung Wan
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Natural Products and Experimental Therapeutics Program, University of Hawaii Cancer Center , Honolulu, Hawaii 96813, United States.
authors.forename: James
authors.initials: J
authors.lastname: Turkson
authors.affiliation: Department of Mechanical Engineering, University of Hawaii at Manoa , Honolulu, Hawaii 96822, United States.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zou
authors.affiliation: Department of Mechanical Engineering, University of Hawaii at Manoa , Honolulu, Hawaii 96822, United States.
authors.forename: Yi Y
authors.initials: YY
authors.lastname: Zuo
authors.affiliation: College of Pharmacy & Health Sciences, Campbell University , Buies Creek, North Carolina 27506, United States.
authors.forename: Rahul V
authors.initials: RV
authors.lastname: Haware
authors.affiliation: Translational Drug and Gene Delivery Research (TransDGDR) Laboratory, Department of Pharmaceutical Sciences, Department of Pharmaceutics and Drug Delivery, Research of Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi , University, Mississippi 38677, United States.|Translational Drug Delivery Research (TransDDR) Laboratory, Department of Pharmaceutical Sciences, The Daniel K. Inouye College of Pharmacy, University of Hawai'i at Hilo , Hilo, Hawaii 96720, United States.|Natural Products and Experimental Therapeutics Program, University of Hawaii Cancer Center , Honolulu, Hawaii 96813, United States.|Pii Center for Pharmaceutical Technology, Research Institute of Pharmaceutical Sciences, University of Mississippi , University, Mississippi 38677, United States.|National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, University of Mississippi , University, Mississippi 38677, United States.
authors.forename: Mahavir B
authors.initials: MB
authors.lastname: Chougule
mesh_terms: D020106:Acrylamide / Q000737:chemistry*; D001120:Arginine / Q000737:chemistry*; D001572:Benzofurans / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry*; D005047:Etoposide / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*
chemical_list: C493999:6-Aminobutylphthalide; D001572:Benzofurans; D004337:Drug Carriers; D011108:Polymers; D020106:Acrylamide; D005047:Etoposide; D001120:Arginine
keywords: Taguchi factorial design; anticancer drugs; bioresponsive; multiple linear regression; multivariate model; nanocarrier; optimization