RAJIV GANDHIUNIVERSITY OF HEALTH SCIENCES

BENGALURU, KARNATAKA

S J M COLLEGE OF PHARMACY

CHITRADURGA-577502

A PROTOCOL FOR THE PROJECT WORK ENTITLED

FORMULATION CHARACTERIZATION AND EVALUATION OF NANOPARTICLES OF ANTI-TUMOUR DRUG

By,

N.RAGHAVENDRA NAVEEN

M. Pharm Part–I

Department of Pharmaceutics

S J M College of Pharmacy

Chitradurga–577 502

RAJIV GANDHIUNIVERSITY OF HEALTH SCIENCES,

BENGALURU, KARNATAKA.

ANNEXURE- II

PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION

1 / Name of the candidate and address
(in block letters) / N.RAGHAVENDRA NAVEEN
Department Of Pharmaceutics S J M College Of Pharmacy
S J M I T Campus
Chitradurga -577502
2 / Name of the Institution / S J M College Of Pharmacy
S J M I T Campus
Chitradurga-577502
3 / Course of study and subject / Master Of Pharmacy In Pharmaceutics.
4 / Date of admission to course / JULY 29th2011
5 / Title of topic / FORMULATION CHARACTERIZATION AND EVALUATION OF NANOPARTICLES OF ANTI-TUMOUR DRUG
6
7 / BRIEF RESUME OF THE INTENDED WORK
6.1. Need for the study
Poorly soluble drugs are a general problem in pharmaceutical drug formulationand it is expected to increase because approximately 40% or more of the new chemical entities being generated through drug discovery programmes are poorly water-soluble. Typical problems associated with poorly soluble drugs are a too low bioavailability and/or erratic absorption. Hence for the drugs with poor solubility and bioavailability can be improvised by the application of nanotechnology. Size reduction process increases the surface area of drug particles and improves the dissolution rate. 1.
Nanoparticles are defined as colloidal dispersions or solid particles with a size in the range of 10-1000nm. Nanotechnology is a multidisciplinary scientific undertaking, involves creation and utilization of materials, devices, or systems on the nanometer scale. Nanoparticles represent a promising drug delivery system of controlled and targeted release. 2-4. On the other hand, polymeric nanoparticles offer some specific advantages over liposomes. For instance, they help to increase the stability of drugs/proteins and possess useful controlled release properties 5, 6.
Cancer is a term used for diseases in which abnormal cells divide without control and are able to invade other tissues. Cancer is not just one disease but many diseases.
Treatment of cancer includes chemotherapy, radiation therapy, gene therapy, photodynamic therapy, biologic therapy, surgical removal of tumor cells, etc. The main problem with anti-cancer drugs is that they not only affect the cancerous cells but also affect the normal cells. These happen due to non-specific targeting to cancerous cells and hence other normal cells get affected.
Targeted delivery of nanoparticles can significantly improve the therapeutic efficacy and safety of drugs.Attempt will be made to target and deliver an anti-cancer drug to cancerous cells so as to minimize dose required for the therapy, adverse effects and also dosing frequency. This will be achieved by formulating polymeric nanoparticles which contains an anticancer drug.
Nanoparticles have been used to successfully smuggle a powerful cancer drug into tumor cells - leaving healthy cells unharmed - is one of the first therapeutic uses for nanotechnology in living animals. A critical advantage in treating cancer with nanoparticles is largely through the inherent leaky vasculature present serving cancerous tissues. The defective vascular architecture, created due to rapid vascularization necessary to serve fast-growing cancers, coupled with poor lymphatic drainage allows an enhanced permeation and retention effect.7
Nanosystems with different compositions and biological properties have been extensively investigated for drug and gene delivery applications. Several anticancer drugs, including paclitaxel, doxorubicin, 5-fluorouracil, and dexamethasone, have been successfully formulated using Nanomaterials1.
6.2. Review of the study
Krishna R.S.M et al.,8 Studied on nanoparticles as a novel drug delivery system that includes the goal of controlled drug delivery as well as site-specific delivery concluded that nanotechnology opens up new vistas of research in the development of novel colloidal drug delivery systems.
Mary J.N et al.,9 Observed on development and evaluation of nanoparticles of mitomycin–c to investigate the preparation of nanoparticles as a potential drug carrier in the treatment of cancer concluded that optimization of the nanoparticles is a complex process, which requires consideration of large number of factors and their interaction with each other.
Chang et al.,10studied the preparation and preliminary characterization of concentric multi-walled chitosan microspheres. Their study revealed that the formulation of chitosan as concentric multi-walled microspheres does not induce high 5-FU loading ratios (≈ 3 %). In addition, the release of the drug from the particles (270 – 370 μm) was very fast (≈ 80 % after 80 min).
Yan et al.,11 also observed good antitumor activity against Sarcoma 180 solid tumor and mild toxicity in 5-FU-loaded N-succinylchitosan nanoparticles prepared by an emulsification solvent diffusion method (average diameter ≈ 250 nm and, loading capacity and highest extent of release: 19 %, and 61 % at 24 h., respectively).
Chitosan particles had been successfully assayed in vivo with very promising tumor inhibition rates. Zhang et al.,12 prepared 5-FU-loaded chitosan-polyaspartic acid nanoparticles of ≈ 200 nm by ionic gelation of chitosan and obtained a loading efficiency of ≈ 40 %. These nanoparticles developed a sustained release during 6 days and the observed tumor inhibition rate was much higher than the anticancer drug alone.
Bhawanaet al.,13developed a method for the preparation of nanoparticles of curcumin with a view to improve its aqueous-phase solubility and examine the effect on its antimicrobial properties. Nanoparticles of curcumin (nanocurcumin) were prepared by a process based on a wet-milling technique and were found to have a narrow particle size distribution in the range of 2−40 nm and mechanism of antibacterial action of curcumin nanoparticles was investigated by transmission electron micrograph (TEM) analysis, which revealed that these particles entered inside the bacterial cell by completely breaking the cell wall,leading to cell death.
M.Sivabalan et al.,14formulated and evaluated nanoparticles of 5-fluorouracil by using polymers like chitosan and eudarit for cancer therapy using polymers like Chitosan, in different concentrations. The physical characteristics , drug loading, drug release pattern were studied.
Krishna A.Sailaja et al.,15 prepared carbapol coated nanoparticles by emulsion polymerization techinique. Morphology of nanoparticles was observed by using SEM ( Scanning electron microscope), physical status of carbapol nanoparticles was determined by using an X-ray diffractomer.
Rajat Sharma et al.,16 Formulated and evaluated Paclitaxel loaded PSA-PEG nanoparticlesby nanoprecipitation method The influence of different experimental parameters on the particles size, entrapment efficiency, percent drug released etc was evaluated.
Adlin jinni nesalin j et al.,17formulated evaluated nanoparticles containing Flutamide, which were formulated using chitosan polymer by ionic gelation technique. Nanoparticles of different core: coat ratio were formulated and analyzed for total drug content, loading efficiency, particle size and in vitro drug release studies.
S. Debnathi et al.,18 done Studies on the Preparation and Evaluation of Chitosan Nanoparticles containing Cytarabine.These nanoparticles prepared by ionotropic gelation were characterized by SEM and evaluated for In vitro Drug Releasekinetics of Drug Release.
6.3 Objective of the study
The objectives of the present investigation are
  • To design suitable formulation of nanoparticles for anti-cancer drug.
  • To characterize formulated nanoparticles for particle size, morphology.
  • Evaluation of developed nanoparticles like Drug loading efficiency, In-vitro drug release, In-vitro release kinetics, Drug – polymer interaction studies, Stability studies for selected batch.
MATERIALS AND METHODS
7.1Source of data
  • National and International journals.
  • CD ROM
  • Internet browsing
  • Helinet
  • From available literature.
  • From library based books.
  • Method of collection of data (including sampling procedure, if any)
Step 1:
Formulation of nanoparticles forselectedanti-cancer drugby any one of suitable following methods.
  1. Solvent emulsification method.
  2. Solvent evaporation method.
  3. Co precipitation method.
  4. Nano encapsulation method etc
  5. Ionic gelation method.
Step 3:
Formulations will be subjected to characterize parameters such
  1. Particle size,
  2. Morphology,
Step 4:
Formulations will be subjected to evaluation parameters such
  1. Drug loading efficiency.
  2. In-vitro drug release.
  3. In-vitro release kinetics.
  4. Drug – polymer interaction studies.
  5. Stability studies for selected batch.
  6. Does the study require any investigation or inventions to be conducted on patients or other human or animals? If so, please describe briefly.
No.
7.4Has ethical clearance been obtained from your institution in case of 7.3?
Not applicable.
LIST OF REFERENCES
  1. R Ravichandran. Nanotechnology-Based Drug Delivery Systems. Nanobiotechnol. 2009; 5:17–33.
  2. Langer R. Biomaterials in drug delivery and tissue engineering: one laboratory's experience. Acc Chem Res 2000; 33: 94-101.
  3. Bhadra D, Bhadra S, Jain P, Jain NK. Pegnology: a review of PEG-ylated systems. Pharmazie 2002; 57: 5-29.
  4. Kommareddy S, Tiwari SB, Amiji MM. Long-circulating polymeric nanovectors for tumor-selective gene delivery. Technol Cancer Res Treat 2005; 4: 615-25.
  5. Vila A, Sanchez A, Tobio M, Calvo P, Alonso MJ. Design of biodegradable particles for protein delivery. J Control Release 2002; 78: 15-24.
  6. Mu L, Feng SS. A novel controlled release formulation for the anticancer drug paclitaxel (Taxol(R)): PLGA nanoparticles containing vitamin E TPGS. J Control Release 2003; 86: 33-48
  7. Bill Denny (Cancer Research Laboratory) and Heather Wansbrough and based on: Denny, William A.; New Directions in Cancer Chemotherapy; Chemistry in New Zealand 1995. Denny, William A.; The Design and Development of Anticancer Drugs; Chemical Processes in New Zealand, edition one, volume twoXII-Biotech-J-Cancer Drugs-1& 2.
  8. Krishna,R.S.M.,Shivakumar,H.G.,Gowda,D.V. and Banerjee,S.,2006. Nanoparticles: A Novel Colloidal Drug Delivery System,Indian Journal of Pharmaceutical Education and Research,40(1),15-21.
  9. Mary,J.N.,Palani,S.,Sharma,PK. and Gupta,MK., 2006. Development and Evaluation of Nanoparticles of Mitomycin-C,Journal of Pharmaceutical Research,5(2),53-56.
  10. Chang SJ, Niu GC, Kuo SM, Chen SF. Preparation and preliminary characterization of concentric multi-walled chitosan microspheres. J Biomed Mater Res A 2007 Jun 1;81(3):554-66.
  11. Yan C, Chen D, Gu J, Qin J. Nanoparticles of 5-fluorouracil (5-FU) loaded N-succinyl (Suc-Chi) for cancer chemotherapy: preparation, characterization – in vivo drug release and antitumour activity. J Pharm Pharmacol 2006 Sep;58(9):1177-81.
  12. Zhang DY, Shen XZ, Wang JY, Dong L, Zheng YL, Wu LL. Preparation of chitosan-polyaspartic acid-5-fluorouracil nanoparticles and its anti-carcinoma effect on tumor growth in nude mice. World J Gastroenterol 2008 Jan 14;14(22):3554-62.
  13. Bhawana, Rupesh Kumar Basniwal, Harpreet Singh Buttar, V. K. Jain, and Nidhi Jain. Curcumin Nanoparticles: Preparation, Characterization, and Antimicrobial Study. J. Agric. Food Chem 2011;59;2056–2061.
  14. M.Sivabalan, Anto shering, Phaneendhar Reddy, vasudevaiah, Anup Jose and G Nigila: Formulation and evaluation of nanoparticles of 5-fluorouracil loaded chitosan and eudarit for cancer therapy International journal comprehensive pharmacy, Volume 2, Issue 1, Article 07, September-October 2011.
  15. Krishna A.Sailaja, P.Amareshwar and M.Dakshayani : Preparation of carbapol coated nanoparticles by emulsion polymerization techinique: International journal of pharmaceutical sciences review and research, Volume 2, Issue 7,2011; 1786-1789
  16. Rajat Sharma, Mohd Yasir, Sanjay Bhaskar and Mohd Asif :Formulation and evaluation of Paclitaxel loaded PSA-PEG nanoparticlesby nanoprecipitation method: Journal of Applied Pharmaceutical Science 01 (05); 2011: 96-98
  17. Adlin jino nesalin j, Gowthamarajan K and Somashekhara C.N.formulation and evaluation of nanoparticles containing Flutamide using chitosan polymer by ionic gelation technique. International Journal of ChemTech ResearchVol.1, No.4, pp 1331-1334, Oct-Dec 2009:
  18. S. Debnathi, D. Datta, M.N. Babu, R.S. Kumar, V. Senthildone Studies on the Preparation and Evaluation of Chitosan Nanoparticles containing Cytarabine. International Journal of Pharmaceutical Sciences and Nanotechnology Volume 3-Issue 2-July - September 2010: 957-964

9. / SIGNATURE OF CANDIDATE / (Mr. N.RAGHAVENDRA NAVEEN)
10. / REMARK OF THE GUIDE:
The proposed work of the candidate is original and has not been submitted to this University / any other University for the award of Degree. It is intended to train the candidate for gaining basic knowledge of planning, organization and experimentation to present this research work in form of dissertation systematically.
11. / NAME AND DESIGNATION OF
11.1 GUIDE / Mr.T.S.NAGARAJA M.Pharm.
H O D., Asst. Proffesor.
Dept. Of Pharmaceutics
S J M College Of Pharmacy
S J M I T Campus
Chitradurga.
11.2 SIGNATURE
11.3 CO-GUIDE
11.4 SIGNATURE
11.5 HEAD OF THE DEPARTMENT / Mr.T.S.NAGARAJA M.Pharm.
H O D., Asst. Proffesor.
Dept. Of Pharmaceutics
S J M College Of Pharmacy
S J M I T Campus
Chitradurga.
11.6 SIGNATURE
12. / 12.1 REMARK OF THE CHAIRMAN AND PRINCIPAL
The above mentioned information is correct and I recommend the same for approval.
12.2 SIGNATURE / Dr.BHARATHI D.R. M. Pharm.PhD.
Professor and Principal
S J M College Of Pharmacy
S J M I T Campus
Chitradurga.