Developed Galantamine Therapy for Alzheimer's Disease by Introducing Nano-Drug Delivery Systems
DOI:
https://doi.org/10.12970/2310-8231.2016.04.01.4Keywords:
Alzheimer (Alz), Ceria-doped calcium hydroxyapatite (Ce/Ca-HAp), Carboxymethyl Chitosan/Ceria/hydroxyapatite composite (CMCS/Ce/Ca-HAp), Galantamine, Rat, Histology and Biochemistry.Abstract
The major cause of dementia, a major public health problem, is Alzheimer’s disease (AD). A reliable method for the diagnosis and follow-up of Alzheimer’s disease is needed together with a specific biological marker. Galantamine, an acetylcholinesterase inhibitor for AD therapy has several reported side effects. One approach to reduce dosing amounts, frequency of administration, and adverse side effects while maintaining the drug efficiency, is the development of drug delivery systems using nanoparticles. Presently Galantamine (Gal) coated with either Cerium/ Calcium hydroxyapatite (Ce/Ca-HAp) or carboxymethyl chitosan/ Ceria/ Calcium hydroxapatite (CMCS/Ce/Ca-HAP) was i.p. injected at a dose of 2.5 mg/kg b.wt. for 2 and 4 weeks. 86 female adult albino Wistar rats (189- 200 gm weight) were used. Alzheimer was induced in ovariectomized rats by Aluminium chloride (AlCl3) oral treatment at doses of 17mg/kg b.wt. daily for 2 months. Rats were divided into six groups: Group (1) normal control; Group (2) Galantamine i.p. injected at a dose of 2.5 mg/kg b.wt; Group (3) Alzheimer ; Group (4) Alzheimer’s induced rats treated i.p. with Gal; Group (5) Alzheimer’s induced rats treated with Gal. coated with Ce/Ca-HAp; Group (6) Alzheimer’s induced rats treated with Gal. coated with Gal coated with CMCS/Ce/Ca-HAp for 2 and 4 weeks. In the concurrent study, AD induced histological alterations manifested as amyloid plaque formation of different sizes; congestion with perivascular edema; degenerated neurons with diffused gliosis; loss of pyramidal cells; separation of cortical tissue and formation of fibrous glial scar. Several tests may be cumulatively used for early detection as decreased Ach; Bcl2; Tpl; GSH; SOD; CAT; Cyto P450 and increased Ab; Chol; B-FABP; NO; MDA; GSSH. Treatment with Gal coated by Ce/Ca-HAp imposed highly significant improvement to near to normal levels in both histological and biochemical parameters. Gal coated by CMCS/Ce/Ca-HAp failed to encounter obvious ameliorations. In conclusion, brain markers ( Ach; Bcl-2; Aβ; TPL; Chol; B-FABP; NO; MDA) together with brain antioxidants (GSH; SOD; CAT; CytoP450) may impose progressive laboratory testing method besides well known imaging techniques. Galantamine therapy may impose limited improvements thus drug delivery systems Gal coated by Ce/Ca-HAp may aid to minimize dosing amounts, frequency of administration, and adverse side effects of drug while increasing its therapeutic efficacy.
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