Development and evaluation of bio-nanoparticles as novel drug carriers for the delivery of Donepezil

Document Type: Reasearch Paper

Authors

1 Research Scholar, Uttarakhand Technical University, Dehradun, India

2 DIT University, Faculty of Pharmacy, Mussoorie Diversion Road, Dehradun, India

3 3Department of Pharmacognosy, Kumaun University, Bhimtal, India

Abstract

The purpose of the present study was to formulate and evaluate donepezil loaded bio-nanoparticles for effective treatment of Alzheimer’s disease. For the preparation of bio-nanoparticles biomaterial was isolated from fruits of Carica papaya by an economic method. The biomaterial recovered from the concentrate was subjected for various physicochemical properties like color, solubility, color changing point and chemical test. Bio-nanoparticles were prepared by modified nanoprecipitation method in different batches with variable drug/biomaterial ratio. Prepared batches were subjected for various evaluation studies like particle size, zeta potential, scanning electron microscopic studies, transmission electronmicroscopy, surface entrapment, in-vitro diffusion, differential scanning calorimetry and stability. Particle size and zeta potential result revealed that all nanoformulation were within range of 1.808 to 995.1 with slight negative in charge. Scanning electron microscopy and transmission electronmicroscopy report indicate that formulations were spherical in shape with less or no aggregation. Less surface entrapment leads to better drug entrapped inside nanomatrix. Bio-nanoformulations were capable of releasing the drug in a slow sustained manner.  From the present investigation, it may be concluded that biomaterial isolated from fruits of Carica papaya used in the preparation of bio-nanoparticle act as an efficient carriers for deliver donepezil at a controlled rate and may significantly improve the ability to cross blood-brain barrier.

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[1] Berchtold N. C., Cotman C. W., (1998), Evolution in the conceptualization of dementia and Alzheimer's disease: Greco-Roman period to the 1960s. Neurobiol. Aging. 19: 173–89.

[2] Bachman D. L., Wolf P. A., Linn R., Knoefel J. E., Cobb J., Belanger A., (1992), Prevalence of dementia and probable senile dementia of the Alzheimer type in the Framingham Study. Neurology. 42: 115-119.

[3] Liesi E., Hebert L. E., Scherr P. A.,  Beckett L. A., Marilyn S., (1995), Age-specific incidence of Alzheimer’s disease in a community population. JAMA. 273: 1354-1359.

[4] Bachman D. L., Wolf P. A., Linn R. T., Knoefel J. E., Cobb J. L., Belanger A. J., (1993), Incidence of dementia and probable Alzheimer's disease in a general population: the Framingham Study. Neurology. 143: 515–519.

[5] Ernst R. L., Hay J. W., (1994), The US economic and social costs of Alzheimer’s disease revisited. Am. J. Public. Health.  84: 1261-1264.

[6] Pardridge W. M., (1999), Non-invasive drug delivery to the human brain using endogenous blood–brain barrier transport systems. Pharm. Sci. Technol. Today. 2: 49-59.

[7] Partridge W. M., (2009), Alzheimer’s disease drug development and the problem of the blood-brain barrier. Alzheimer’s and Dement.5: 427-432.

[8] Mori N., Kurokouchi A., Osonoe K., Saitoh H., Ariga K., Suzuki K., Iwata Y., (1995),  Liposome entrapped phenytoin locally suppresses amygdaloid epileptogenic focus created by db-CAMP/EDTA in rats. Brain Res.703: 184-190.

[9] Shuting K., Feng Y., Ying W., Yilin S., Nan Y., Ling Y., (2010), The blood-brain barrier penetration and distribution of PEGylated fluorescein-doped magnetic silica nanoparticles in rat brain. Biochem. Biophys. Res.394: 871-876.

[10] Zara G. P., Cavalli R., Bargoni A., Fundaro A., Vighitto D., Gasco M. R., (2002), Intravenous administration to rabbits of non-stealth and stealth doxorubicin loaded solid lipid nanoparticles at increasing concentration of stealth agent: pharmacokinetics and distribution of doxorubicin in brain and in other tissues. J. Drug Target.10: 327-335.

[11] Tian X. H., Lin X. N., Wei F., Feng W., Huang Z. C., Wang P., (2011), Enhanced brain targeting of temozolomide in polysorbate-80 coated polybutylcyanoacrylate nanoparticles. Int. J. Nanomedicine.6: 445-452.

[12] Lefèvre G., Pommier F., Sedek G., Allison M., Huang H. L. A., Beate K., Ho Y. Y., Silke A. D., (2008), Transdermal patch versus rivastigmine oral solution in healthy elderly subjects. J. Clin. Pharmacol.  48: 246-252.

[13] Joshi S. A., Chavhan S. S., Sawant K. K., (2010), Rivastigmine-loaded PLGA and PBCA nanoparticles: Preparation, optimization, characterization, in vitro and pharmacodynamic studies. Eur. J. Pharm. Biopharm.76: 189-199.

[14] Donga Y., Wai K. N., Shen S., Kim S., Tan R. B. H., (2009), Preparation and characterization of spironolactone nanoparticles by antisolvent precipitation. Int. J. Pharm.  244-249.

[15] Tamilselvan N., Raghavan C. V., Balakumar K., Karthik S., (2014), Brain targeted delivery of rivastigmine polymeric nanoprticles through oral administration to treat Alzheimer’s disease. Int. J. Res. Pharmaceut. Nano Sci. 3: 536-551.

[16] Lamprecht A., Yamamoto H., Takeuchi H., Kawashima Y., (2005), Observations in simultaneous microencapsulation of 5-fluorouracil and leucovorin for combined pH-dependent release. Eur. J. Pharm. Biopharm. 59: 367-371.

[17] Zheng W., Zhao L., (2010), Preparation and the in Vitro Evaluation of Nanoemulsion System for the Transdermal Delivery of Granisetron Hydrochloride. Chem. Pharm. Bull. 58: 1015-1019.

[18] Dandagi P., Patel P., Patil P., Mastiholimath V., Gadad A., (2011),  Development and characterization of a particulate drug delivery systemfor etoposide.  Indian J. Novel Drug Delivery.  3: 43–51.

[19] Allemann E., Gurny R., Deolker E., (1993), Drug loaded nanoparticles: preparation methods and drug targeting issues. Eur. J. Pharm. Biopharm. 39: 173-179.

[20] Banerjee T., Mitra S., Singh A. K., Sharma R. K., Maitra A., (2002), Preparation and biodistribution of ultrafine chitosan nanoparticles. Int. J. Pharm. 243: 93-105.

[21] Baumgartner S., Vrecer  F., Zoroko B., (2000), Optimization of floating matrix tablets and evaluation of their gastric residence time. Int. J. Pharm. 195: 125-135.