title: Development and optimization of polymeric self-emulsifying nanocapsules for localized drug delivery: design of experiment approach.
abstract: The purpose of the present study was to formulate polymeric self-emulsifying curcumin nanocapsules with high encapsulation efficiency, good emulsification ability, and optimal globule size for localized targeting in the colon. Formulations were prepared using modified quasiemulsion solvent diffusion method. Concentration of formulation variables, namely, X1 (oil), X2 (polymeric emulsifier), and X3 (adsorbent), was optimized by design of experiments using Box-Behnken design, for its impact on mean globule size (Y1) and encapsulation efficiency (Y2) of the formulation. Polymeric nanocapsules with an average diameter of 100-180 nm and an encapsulation efficiency of 64.85±0.12% were obtained. In vitro studies revealed that formulations released the drug after 5 h lag time corresponding to the time to reach the colonic region. Pronounced localized action was inferred from the plasma concentration profile (C max 200 ng/mL) that depicts limited systemic absorption. Roentgenography study confirms the localized presence of carrier (0-2 h in upper GIT; 2-4 h in small intestine; and 4-24 h in the lower intestine). Optimized formulation showed significantly higher cytotoxicity (IC50 value 20.32 μM) in HT 29 colonic cancer cell line. The present study demonstrates systematic development of polymeric self-emulsifying nanocapsule formulation of curcumin for localized targeting in colon.
authors.affiliation: MM College of Pharmacy, MM University, Mullana, Ambala 133207, India.
authors.forename: Jyoti
authors.initials: J
authors.lastname: Wadhwa
authors.affiliation: MM College of Pharmacy, MM University, Mullana, Ambala 133207, India.
authors.forename: Abhay
authors.initials: A
authors.lastname: Asthana
authors.affiliation: MM College of Pharmacy, MM University, Mullana, Ambala 133207, India.
authors.forename: Sumeet
authors.initials: S
authors.lastname: Gupta
authors.affiliation: MM College of Pharmacy, MM University, Mullana, Ambala 133207, India.
authors.forename: Gyati
authors.initials: G
authors.lastname: Shilkari Asthana
authors.affiliation: Government College of Pharmacy, Rohru, Shimla 171207, India.
authors.forename: Ranjit
authors.initials: R
authors.lastname: Singh
mesh_terms: D000818:Animals; D002152:Calorimetry, Differential Scanning; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003474:Curcumin / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D045703:Emulsifying Agents / Q000737:chemistry*; D041981:Gastrointestinal Tract / Q000000981:diagnostic imaging / Q000187:drug effects; D006168:Guinea Pigs; D019073:HT29 Cells; D006801:Humans; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D053769:Nanocapsules / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D011859:Radiography; D012044:Regression Analysis; D012995:Solubility; D014961:X-Ray Diffraction
chemical_list: D045703:Emulsifying Agents; D053769:Nanocapsules; D011108:Polymers; C048331:hydroxypropylmethylcellulose acetate succinate; D008747:Methylcellulose; D003474:Curcumin