Improved oral therapeutic potential of nanoencapsulated cryptdin formulation against Salmonella infection.
An encapsulated system for cryptdin-2 (a Paneth cell antimicrobial peptide) was developed, with a view to help it sustain adverse gut conditions and to ensure its bioavailability on oral administration. The formulation was characterized on the basis of particle size, zeta potential and polydispersity index. Cryptdin-2 loaded nanoparticles of size 105±7 nm, formulated by ionotropic gelation method using chitosan: tripolyphosphate (5:2), revealed 60% drug entrapment efficiency with 65% in vitro release in 4.5 h. Developed system was evaluated for its therapeutic application against Salmonella Typhimurium infection in mice, on the basis of survivability of animals, bacterial load in tissues, histo-architecture and oxidative damage markers. Infected mice when treated with the encapsulated peptide showed 83% survivability and approximately 2 log unit reductions in the bacterial load in the tissues versus 100% mortality observed with the free peptide. The encapsulated cryptdin-2 also achieved a decrease in the level of oxidants, particularly nitrite by 3.25 folds and increased the level of antioxidant catalase by 2 folds when compared to the levels exhibited by the free peptide. The bacteriological and biochemical alterations illustrated by encapsulated peptide co-related well with the histo-architectural studies. The study is a first pre-clinical report on the oral effectiveness of cryptdin-2 by its suitable encapsulation and has potential for future clinical applications.
Department of Microbiology, Panjab University, Chandigarh, India. Electronic address: rishipraveen@yahoo.com.
Praveen
P
Rishi
Department of Microbiology, Panjab University, Chandigarh, India.
Akanksha
A
Bhogal
Department of Microbiology, Panjab University, Chandigarh, India.
Sumeha
S
Arora
Department of Microbiology, Panjab University, Chandigarh, India.
Satish K
SK
Pandey
Department of Biochemistry, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
Indu
I
Verma
University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Indu Pal
IP
Kaur
D000284:Administration, Oral; D000818:Animals; D058491:Bacterial Load / Q000187:drug effects; D048271:Chitosan / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D023082:Defensins; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D065546:Drug Liberation; D007422:Intestines / Q000187:drug effects / Q000382:microbiology; D008099:Liver / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D011122:Polyphosphates / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D011506:Proteins / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D012481:Salmonella Infections, Animal / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D012485:Salmonella typhi / Q000187:drug effects
D023082:Defensins; D004337:Drug Carriers; D011122:Polyphosphates; D011506:Proteins; C107641:cryptdin 2; D048271:Chitosan; C005692:triphosphoric acid
Chitosan; Cryptdin-2; Histological studies; In-vivo; Nanoparticles; Oxidative damage