title: Development and performance evaluation of novel nanoparticles of a grafted copolymer loaded with curcumin.
abstract: Inflammatory bowel disease (IBD) is an inflammatory condition with mucosal ulceration, edema and hemorrhage of gastrointestinal tract. Curcumin has been shown to mitigate colitis in animal models. However, its usefulness is reduced due to poor pharmacokinetic behavior and low oral bioavailability. To address this, novel pH-sensitive hydrolyzed polyacrylamide-grafted-xanthan gum (PAAm-g-XG) nanoparticles (NPs) loaded with curcumin were prepared for colonic delivery. Optimized nanoparticles (CN20) were spherical, with an average size of 425 nm. A negligible amount of curcumin (≈8%) was released from CN20 NPs in pH 1.2 and 4.5 solutions. When the pH was increased to 7.2, curcumin release was comparatively faster than that observed with pH 1.2 and 4.5 collectively. In pH 6.8 solution, excellent release of curcumin was observed. Highest curcumin release was observed when rat caecal contents were incorporated in pH 6.8 solution, indicating microflora-dependent drug release property of NPs. In acetic acid-induced IBD in rats, curcumin NPs reduced myeloperoxidase and nitrite levels, prevented weight loss and attenuated colonic inflammation. Curcumin was better absorbed systemically in nanoparticulate form with increased Cmax (∼3 fold) and AUC (∼2.5 fold) than when delivered as free curcumin. We demonstrate successful development of grafted co-polymeric NPs containing drug suitable for colon targeting.
authors: Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, 576104 Karnataka, India. Electronic address: ss.mutalik@manipal.edu.
authors: Srinivas
authors: S
authors: Mutalik
authors: Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, 576104 Karnataka, India.
authors: Neelam A
authors: NA
authors: Suthar
authors: Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, 576104 Karnataka, India.
authors: Renuka S
authors: RS
authors: Managuli
authors: Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, 576104 Karnataka, India.
authors: Pallavi K
authors: PK
authors: Shetty
authors: Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, 576104 Karnataka, India.
authors: Kiran
authors: K
authors: Avadhani
authors: Department of Clinical Embyology, Kasturba Medical College, Manipal University, Manipal, 576104 Karnataka, India.
authors: Guruprasad
authors: G
authors: Kalthur
authors: Department of Pharmaceutical Technology, BLDE College of Pharmacy, BLDE University Campus, Bijapur, Karnataka, India.
authors: Raghavendra V
authors: RV
authors: Kulkarni
authors: University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, QLD 4102, Australia.
authors: Ranjeny
authors: R
authors: Thomas
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000737:chemistry; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002712:Chlorides / Q000737:chemistry; D002522:Chlorocebus aethiops; D003106:Colon / Q000033:anatomy & histology / Q000187:drug effects; D003474:Curcumin / Q000737:chemistry* / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics; D004339:Drug Compounding; D065546:Drug Liberation; D045325:HCT116 Cells; D006801:Humans; D006868:Hydrolysis; D008297:Male; D053758:Nanoparticles / Q000737:chemistry* / Q000378:metabolism; D036103:Nanotechnology; D009573:Nitrites / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010316:Particle Size; D009195:Peroxidase / Q000378:metabolism; D011135:Polysaccharides, Bacterial / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D014709:Vero Cells; D014867:Water / Q000737:chemistry; D000099166:Polyacrylamides
chemical_list: D000180:Acrylic Resins; D000077410:Aluminum Chloride; D017607:Aluminum Compounds; D002712:Chlorides; D003474:Curcumin; D004337:Drug Carriers; D009573:Nitrites; D009195:Peroxidase; D011135:Polysaccharides, Bacterial; D014867:Water; D000099166:Polyacrylamides; C002563:xanthan gum
keywords: Curcumin; Grafted copolymer; Inflammatory bowel disease; Nanoparticles; Polyacrylamide; Xanthan gum