Vesicular Biologically Active Compounds in Combating Mitochondrial Oxidative Damage in Cellular Diseases
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
Vesicular Biologically Active Compounds in Combating
Mitochondrial Oxidative Damage in Cellular Diseases
|
|
| Creator |
Biswas (Ghosh), Swarupa
|
|
| Subject |
Cell Biology & Physiology
Drug Development/Diagnostics & Biotechnology |
|
| Description |
Mitochondrion, the powerhouse of the cell is an important cell survival regulator. Pathophysiological conditions like cerebral ischemia-reperfusion, aging associated neurodegeneration, cancer, heavy metal toxicity comes with varied symptoms but mitochondrial damage remains a common consequence. Uses of biologically active compounds of natural origin aimed at treating dysfunctioning mitochondria in different cellular disorders remain a challenge due to various limitations.
The present research work was designed to elucidate, optimise and evaluate the efficacy of vesiculated drug formulations containing biologically active compounds against mitochondrial oxidative damage in brain and/or liver and its possible protection mechanism in rat model.
CDP-choline, a neuroprotectant was encapsulated in mannose residue conjugated liposome to facilitate specific binding of liposomes to mannose receptors in brain cells. Mannosylated liposomal CDP-choline (diameter < 100nm) protected brain cells from cerebral ischemia-reperfusion (CI-R) induced oxidative damage in young and aged rats by protecting mitochondrial membrane integrity and preventing cytochrome c release to the cytosol.
Oral pretreatment of Ginkgolide b polymeric nanocapsules (NGB) could efficiently control CI-R induced cerebral edema and hippocampal neuronal loss in young and aged rat brain. NGB being able to cross blood brain barrier, ensured a sustained presence of the drug at brain cells. NGB guarded dysfunctioning of mitochondria due to CI-R, downregulated iNOS expression and DNA fragmentation in neuronal cells.
Quercetin a polyphenolic antioxidant was incorporated in polymeric nanocapsules tagged with mitochondria specific lipophilic-cation triphenylphosphonium. Selective delivery of quercetin to brain mitochondria preserved the hippocampal neurons from CI-R induced degeneration, prevented mitochondrial dysfunction.
Coencapsulation of Quercetin with an arsenic chelator meso 2, 3-dimercaptosuccinicacid in polymeric nanocapsules facilitated their simultaneous delivery. Coencapsulation showed synergistic effect in the management of toxicity due to chronic arsenic accumulation and ROS mediated hepatic and neuronal mitochondrial dysfunction and p53 activation in rats.
Chemical carcinogen diethylnitrosamine administration was found to be the key factor in controlling mitochondrial redox status, inflammation, cell proliferation and neoangiogenesis in rat liver. Efficient “cargo unloading” at hepatic mitochondria by nanocapsulated GB could prevent diethylnitrosamine induced mitochondrial dysfunction associated inflammation and neoangiogenesis.
Thus vesicular drug targeting with naturally occurring compounds appear as a promising means of addressing mitochondrial diseases.
|
|
| Date |
2012
|
|
| Type |
Thesis
NonPeerReviewed |
|
| Format |
application/pdf
|
|
| Identifier |
http://www.eprints.iicb.res.in/1867/2/final_thesis.pdf
Biswas (Ghosh), Swarupa (2012) Vesicular Biologically Active Compounds in Combating Mitochondrial Oxidative Damage in Cellular Diseases. PhD thesis, Calcutta University. |
|
| Relation |
http://www.eprints.iicb.res.in/1867/
|
|