TY - JOUR
T1 - Stimuli-Responsive Nanocapsules for the Spatiotemporal Release of Melatonin
T2 - Protection against Gastric Inflammation
AU - Pramanik, Sumit Kumar
AU - Pal, Uttam
AU - Choudhary, Preety
AU - Singh, Harwinder
AU - Reiter, Russel J.
AU - Ethirajan, Anitha
AU - Swarnakar, Snehasikta
AU - Das, Amitava
N1 - Funding Information:
Financial support from the SERB grants (EMR/2016/001850 and JCB/2017/000004) and DBT (India) grant (BT/PR22251/NNT/28/1274/2017) is acknowledged by A.D. Financial support from SERB (PDF/2015/000745) and BOF is acknowledged by S.K.P.
Publisher Copyright:
© 2019 American Chemical Society.
PY - 2019/12/16
Y1 - 2019/12/16
N2 - Melatonin is a secretory product of the pineal gland that regulates circadian rhythm. It is also well-known for its anti-inflammatory and antioxidant properties against the damaging influences of reactive oxygen species. To improve its therapeutic efficacy, a new formulation with melatonin loaded in a stimuli-responsive polymeric nanocapsule has been prepared following an inverse mini-emulsion technique. The colloidal stability of the melatonin-loaded nanocapsules (MNCs) is studied using dynamic light scattering, while the morphology of these MNCs is characterized using various electron microscopies. These MNCs have an inner diameter of 80-120 nm with a cell wall thickness of 29 ± 11 nm. The emission band maximum for melatonin appears at 350 nm following excitation at 305 nm (quantum yield, φ350 = 0.13). The self-quenching nature of the entrapped melatonin molecules inside the nanocapsules attributes to a lower φ350 value for the MNCs. The controlled release of melatonin from MNCs in an in vitro condition is achieved by inducing a rupture of the polymeric backbone through maintaining a certain media pH (∼2.0-4.0) as an external stimulus, and this accounts for a significant enhancement in its characteristic luminescence. The H,K-ATPase, an integral membrane protein, maintains this specific pH range in the interior of the gastrointestinal tract. This methodology is adopted for developing an efficient drug delivery process in the gastric environment. A significant improvement in the AGS cell survival under oxidative stress conditions is observed during preincubation with MNCs compared to free melatonin. In a murine model of the stress-induced gastric ulcer, MNCs outperformed free melatonin in terms of drug efficacy. The value for the gastric ulcer index is reduced from ∼30 to ∼15 by free melatonin and from ∼30 to ∼8 by MNCs treatments, respectively. Such formulation could be a step forward for developing more efficient melatonin-based gastroprotective supplements.
AB - Melatonin is a secretory product of the pineal gland that regulates circadian rhythm. It is also well-known for its anti-inflammatory and antioxidant properties against the damaging influences of reactive oxygen species. To improve its therapeutic efficacy, a new formulation with melatonin loaded in a stimuli-responsive polymeric nanocapsule has been prepared following an inverse mini-emulsion technique. The colloidal stability of the melatonin-loaded nanocapsules (MNCs) is studied using dynamic light scattering, while the morphology of these MNCs is characterized using various electron microscopies. These MNCs have an inner diameter of 80-120 nm with a cell wall thickness of 29 ± 11 nm. The emission band maximum for melatonin appears at 350 nm following excitation at 305 nm (quantum yield, φ350 = 0.13). The self-quenching nature of the entrapped melatonin molecules inside the nanocapsules attributes to a lower φ350 value for the MNCs. The controlled release of melatonin from MNCs in an in vitro condition is achieved by inducing a rupture of the polymeric backbone through maintaining a certain media pH (∼2.0-4.0) as an external stimulus, and this accounts for a significant enhancement in its characteristic luminescence. The H,K-ATPase, an integral membrane protein, maintains this specific pH range in the interior of the gastrointestinal tract. This methodology is adopted for developing an efficient drug delivery process in the gastric environment. A significant improvement in the AGS cell survival under oxidative stress conditions is observed during preincubation with MNCs compared to free melatonin. In a murine model of the stress-induced gastric ulcer, MNCs outperformed free melatonin in terms of drug efficacy. The value for the gastric ulcer index is reduced from ∼30 to ∼15 by free melatonin and from ∼30 to ∼8 by MNCs treatments, respectively. Such formulation could be a step forward for developing more efficient melatonin-based gastroprotective supplements.
KW - animal model
KW - drug release
KW - gastric ulcer
KW - melatonin
KW - nanocapsules
KW - pH-responsive
KW - targeted delivery
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U2 - 10.1021/acsabm.9b00236
DO - 10.1021/acsabm.9b00236
M3 - Article
AN - SCOPUS:85077181622
VL - 2
SP - 5218
EP - 5226
JO - ACS Applied Bio Materials
JF - ACS Applied Bio Materials
SN - 2576-6422
IS - 12
ER -