title: Supercritical anti-solvent technique assisted synthesis of thymoquinone liposomes for radioprotection: Formulation optimization, in-vitro and in-vivo studies.
abstract: The aim of this study was to develop Thymoquinone (TQ) loaded PEGylated liposomes using supercritical anti-solvent (SAS) process for enhanced blood circulation, and greater radioprotection. The SAS process of PEGylated liposomes synthesis was optimized by Box-Behnken design. Spherical liposomes with a particle size of 195.6±5.56nm and entrapment efficiency (%EE) of 89.4±3.69% were obtained. Optimized SAS process parameters; temperature, pressure and solution flow rate were 35°C, 140bar and 0.18mL/min, respectively, while 7.5mmol phospholipid, 0.75mmol of cholesterol, and 1mmol TQ were optimized formulation ingredients. Incorporation of MPEG-2000-DSPE (5% w/w) provided the PEGylated liposomes (FV-17B; particle size=231.3±6.74nm, %EE=91.9±3.45%, maximum TQ release >70% in 24h). Pharmacokinetics of FV-17B in mice demonstrated distinctly superior systemic circulation time for TQ in plasma. Effectiveness of radioprotection by FV-17B in mice model was demonstrated by non-significant body weight change, normal vital blood components (WBCs, RBCs, and Platelets), micronuclei and spleen index and increased survival probability in post irradiation animal group as compared to controls (plain TQ and marketed formulation). Altogether, the results anticipated that the SAS process could serve as a single step environmental friendly technique for the development of stable long circulating TQ loaded liposomes for effective radioprotection.
authors.affiliation: Nanomedicine Research Lab, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India. Electronic address: iqbal_ahmad2@yahoo.co.in.
authors.forename: Iqbal
authors.initials: I
authors.lastname: Ahmad
authors.affiliation: Nanomedicine Research Lab, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India; Centre de Biophysique Moléculaire (CBM)-CNRS UPR4301, Rue Charles Sadron, 45071 Orléans Cedex 2, France. Electronic address: sohailakhtermph@gmail.com.
authors.forename: Sohail
authors.initials: S
authors.lastname: Akhter
authors.affiliation: Nanomedicine Research Lab, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Anwar
authors.affiliation: Nanomedicine Research Lab, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India.
authors.forename: Sobiya
authors.initials: S
authors.lastname: Zafar
authors.affiliation: Division of CBRN Defence, Institute of Nuclear Medicine and Allied Sciences, DRDO, New Delhi, India.
authors.forename: Rakesh Kumar
authors.initials: RK
authors.lastname: Sharma
authors.affiliation: Nanomedicine Research Lab, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India.
authors.forename: Asgar
authors.initials: A
authors.lastname: Ali
authors.affiliation: Nanomedicine Research Lab, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India. Electronic address: farhanja_2000@yahoo.com.
authors.forename: Farhan Jalees
authors.initials: FJ
authors.lastname: Ahmad
mesh_terms: D000818:Animals; D016227:Benzoquinones / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D001772:Blood Cell Count; D001835:Body Weight / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D065546:Drug Liberation; D005720:Gamma Rays / Q000009:adverse effects*; D008081:Liposomes; D008297:Male; D051379:Mice; D015162:Micronucleus Tests; D010714:Phosphatidylethanolamines / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D013154:Spleen / Q000187:drug effects / Q000473:pathology
chemical_list: D016227:Benzoquinones; D008081:Liposomes; C099730:N-carbamylmethoxypoly(ethylene glycol)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine; D010714:Phosphatidylethanolamines; D011837:Radiation-Protective Agents; D011092:Polyethylene Glycols; C003466:thymoquinone
keywords: In-vivo; PEGylated liposomes; Pharmacokinetics; Radioprotection; Supercritical anti-solvent process; Thymoquinone