title: Lecithin-gold hybrid nanocarriers as efficient and pH selective vehicles for oral delivery of diacerein-In-vitro and in-vivo study.
abstract: We report the synthesis and evaluation of lecithin-gold hybrid nanocarriers for the oral delivery of drugs with improved pharmacokinetics, Au-drug interactive bioactivity and controlled drug releasing behavior at physiological pH inside human body. For this purpose, diacerein, a hydrophobic anti-arthritic drug, was loaded in lecithin NPs (LD NPs), which were further coated by Au NPs either by in-situ production of Au NPs on LD NPs or by employing pre-synthesized Au NPs. All LDAu NPs were found to release drug selectively at the physiological pH of 7.4 and showed 2.5 times increase in the oral bioavailability of diacerein. Pharmacological efficacy was significantly improved i.e., greater than the additive effect of diacerein and Au NPs alone. LDAu NPs started suppressing inflammation at first phase, whereas LD NPs showed activity in the second phase of inflammation. These results indicate the interaction of Au NPs with prostaglandins and histaminic mediators of first phase of carrageenan induced inflammation. Acute toxicity study showed no hepatic damage but the renal toxicity parameters were close to the upper safety limits. Toxicity parameters were dependent on surface engineering of LDAu NPs. Apart from enhancing the oral bioavailability of hydrophobic drugs and improving their anti-inflammatory activity, these hybrid nanocarriers may have potential applications in gold-based photothermal therapy and the tracing of inflammation at atherosclerotic and arthritic site.
authors.affiliation: Department of Chemistry, SBA School of Science & Engineering (SBASSE), Lahore University of Management Sciences (LUMS), DHA, Lahore Cantt. 54792 Lahore, Pakistan; Faculty of Pharmacy, Bahauddin Zakariya University, Bosan Road, Multan 60000, Pakistan.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Javed
authors.affiliation: Department of Chemistry, SBA School of Science & Engineering (SBASSE), Lahore University of Management Sciences (LUMS), DHA, Lahore Cantt. 54792 Lahore, Pakistan.
authors.forename: Syed Zajif
authors.initials: SZ
authors.lastname: Hussain
authors.affiliation: Faculty of Pharmacy, Bahauddin Zakariya University, Bosan Road, Multan 60000, Pakistan.
authors.forename: Atif
authors.initials: A
authors.lastname: Shahzad
authors.affiliation: Department of Chemistry, SBA School of Science & Engineering (SBASSE), Lahore University of Management Sciences (LUMS), DHA, Lahore Cantt. 54792 Lahore, Pakistan.
authors.forename: Jahanzeb Muhammad
authors.initials: JM
authors.lastname: Khan
authors.affiliation: Department of Chemistry, SBA School of Science & Engineering (SBASSE), Lahore University of Management Sciences (LUMS), DHA, Lahore Cantt. 54792 Lahore, Pakistan.
authors.forename: Habib
authors.initials: H
authors.lastname: Ur-Rehman
authors.affiliation: Department of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan.
authors.forename: Mubashar
authors.initials: M
authors.lastname: Rehman
authors.affiliation: Drug Delivery System Excellence Center, Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand.
authors.forename: Faisal
authors.initials: F
authors.lastname: Usman
authors.affiliation: Faculty of Pharmacy, Bahauddin Zakariya University, Bosan Road, Multan 60000, Pakistan.
authors.forename: Muhammad Tahir
authors.initials: MT
authors.lastname: Razi
authors.affiliation: H.E.J Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan.
authors.forename: Muhammad Raza
authors.initials: MR
authors.lastname: Shah
authors.affiliation: Department of Chemistry, SBA School of Science & Engineering (SBASSE), Lahore University of Management Sciences (LUMS), DHA, Lahore Cantt. 54792 Lahore, Pakistan. Electronic address: ihussain@lums.edu.pk.
authors.forename: Irshad
authors.initials: I
authors.lastname: Hussain
mesh_terms: D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D000880:Anthraquinones / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D019540:Area Under Curve; D001682:Biological Availability; D003102:Colloids / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D065546:Drug Liberation; D004487:Edema / Q000517:prevention & control; D005121:Extremities / Q000473:pathology; D006046:Gold / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D054709:Lecithins / Q000737:chemistry*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008657:Metabolic Clearance Rate; D053768:Metal Nanoparticles / Q000737:chemistry*; D011817:Rabbits; D051381:Rats
chemical_list: D000880:Anthraquinones; D000893:Anti-Inflammatory Agents; D003102:Colloids; D004337:Drug Carriers; D054709:Lecithins; C025292:diacerein; D006046:Gold
keywords: Arthritis; Diacerein; Nanocarriers; Oral delivery; Pharmacokinetics