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BRIEF RESUME OF THE INTENDED WORK
NEED FOR THE STUDY:
The effectiveness of anticancer agents may be hindered by low solubility in water, poor permeability & high efflux from cells. Nanomaterial have been used to enable drug delivery with lower toxicity to healthy cells & enhanced drug delivery to tumour cells.1
Treatment of cancer includes chemotherapy, radiation therapy, gene therapy, photodynamic therapy, biologic therapy, surgical removal of tumour cells, etc. Cancer treatment vary according to the type of cancer and the extent of the tumour.2
Biodegradable polymeric nanoparticles have shown great therapeutic potential as a drug delivery nano carrier. Biodegradable polymers such as poly (D, L-lactic-co-glycolic acid) (PLGA) and poly (caprolactone) (PCL) have been used in several FDA-approved therapeutic products. Their co-polymers with PEG are commonly used to form core shell structured nanoparticles to encapsulate a variety of therapeutic agents.3
Nanoparticles- particle in the size range 1-1000 nm emerging as a class of therapeutic for cancer .The nanoparticle therapeutics can show enhanced efficacy, while Simultaneously reducing side effects, owing to properties such as more targeted localization in tumour and active cellular uptake. The use of nanoparticles has a number of advantages: targeting, decreasing the doses, availability for parenteral administration, maintaining the therapeutic concentration & limiting the toxic effects.4
Tremendous opportunities exist for using nanoparticles as controlled drug delivery systems for cancer treatment. Natural and synthetic polymers including albumin, fibrinogen, alginate, chitosan and collagen have been used for the fabrication of nanoparticles.5
In comparison to other class of drugs, cytotoxic anticancer drugs present unique problems that come primarily from the relative lack of specificity of their systemic bio distribution and the subsequent side effects provoked by the drug attacking both healthy and target cells.
In addition, their unfavourable pharmacokinetics implies the administration of high drug doses and imposes on patients a rigorous schedule for reaching the desired therapeutic effect.6
These unwanted properties exhibited by free drugs can be summarized in the following points:
The hydrophobic character of many drugs promotes their precipitation in aqueous media;
They suffer of poor selectivity for target tissues;
They undergo bio distribution in a large body volume with severe side effects in
sensitive non target tissues;
Their inadvertent extravasation can produce damage in healthy tissues;
Molecular drugs suffer rapid clearance;
Their in vivo degradation implies the necessity of high dose administration;
Susceptibility to induce drug resistance.6,7
Chemotherapy is the most convenient and less-expensive when compared to other modes of treatment. Varieties of anticancer drugs are available in the market and some of them are under clinical trials. The main problem with anti-cancer drugs is that they not only affect the tumour cells but also affect the normal cells. These happen due to non-specific targeting to tumour cells and hence other normal cells get affected.
Recently, drug targeting especially targeting by nanoparticles have been getting much attention by the researchers for treating cancer. A critical advantage in treating cancer with nanoparticles is 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. Targeting the tumour vasculature is a strategy that can allow targeted delivery to a wide range of tumour types.8
Hence considering the importance of treating cancer, an attempt will be made to target and deliver an anti-cancer drug to these cancerous cells so as to minimize adverse effects, dose and dosing frequency, improved therapeutic index, potentially overcoming resistance associated with anticancer drugs in the form of nanoparticles.
Nanoparticles can be prepared from a variety of materials such as proteins, polysaccharides and synthetic polymers. The selection of matrix materials is dependent on many factors including :
(a) Size of nanoparticles required;
(b) Inherent properties of the drug, e.g., aqueous solubility and stability;
(c) Surface characteristics such as charge and permeability;
(d) Degree of biodegradability, biocompatibility and toxicity;
(e) Drug release profile desired; and
(f) Antigenicity of the final product.9
Nano systems with different compositions and biological properties have been extensively investigated for drug and gene delivery applications. Several anticancer drugs, including paclitaxel, doxorubicin, 5-fluorouracil, vinblastine, chlorambucil, flutamide, methotrexate, 6-mercaptopurine, boswellic acid, cisplatin, etoposide etc… have been successfully formulated using nano materials.
REVIEW OF THE STUDY:
Tamizhrasi S et al.,10 have reviewed on the preparation and evaluation of the polymethacrylic acid nanoparticles containing lamivudine in different drug to polymer ratio by Nano-precipitation method and evaluation by SEM and FT-IR has revealed that average particle size was found to be 121-403nm and there was no chemical interaction
between drug and polymer and stability of drug. The in vitro release behaviour from all the drug loaded batches was found to be zero order and provided sustained release over a period of 24 h.
Potnuru S et al.,11 developed formulation and characterization of novel biodegradable nanoparticles of Stavudine by using solvent evaporation method, in-situ Nano emulsion polymer cross linking method. Drug containing nanoparticles were prepared with different drug polymer ratio at ambient temperature and freeze drying of nanoparticles formulation for long term stability, comparatively based upon the method of preparation the in- situ method has produced a good results like drug loading efficiency, in-vitro release.
Umasanker. K et al.,12 formulated and evaluated Cytarabine nanoparticles.
Cytarabine nanoparticles were formulated by ionic gelation method using polymer chitosan in different ratios. Nanoparticle were characterised by determining its particle size, drug entrapment efficiency, drug release and stability studies.
Sivabalan M. et al.,13 formulated and evaluated nanoparticles of 5-fluorouracil by using polymers like chitosan and eudarit for cancer therapy in different concentrations. The physical characteristics, drug loading & drug release patterns were studied.
Erem Bilensoya et al.,14 Intravesical cationic nanoparticles of chitosan and Polycaprolactone for the delivery of Mitomycin C to bladder tumours. Elation For chitosan nanoparticle ionic gelation and nanoprecipitation method is used and characterisation is for various parameters like particle size distribution, zeta potential, DSC and SEM are performed.
Sompur c.k et al.,15 A novel approach for development and characterisation of Etoposide loaded solid lipid nanoparticles by solvent displacement method by using various concentration of SLNS & evaluated for percentage yield, drug loading, percentage entrapment efficiency, particle size, surface morphology, in vitro release rate studies.
Nilesh M. Mahazan et al.,16 Design and development of mesalamine loaded PLGA nanoparticles. Nanoparticles were prepared using spontaneous emulsification solvent diffusion method. NPS were characterised in terms of surface morphology, particle size and distribution, zeta potential, encapsulation efficiency and drug release profile. X-ray diffraction and differential scanning colorimetry were employed to determine any interaction between drug and polymer.
Vinod Ramani et al.,17 Formulation and evaluation of nanoparticles of HMG-CoA reductase inhibitor. The formulations were done by emulsion- solvent evaporation method followed by freeze drying. The formulated nanoparticle were subjected to characterisation studies like particle size analysis, X-ray diffraction studies, differential scanning colorimetry,SEM and UV analysis.
Rajat Sharma et al.,18 Formulated and evaluated Paclitaxel loaded PSA-PEG nanoparticles by nanoprecipitation method The influence of different experimental parameters on the particles size, entrapment efficiency, percent drug released etc. was evaluated.
Saji Uthaman et al.,19 Novel Boswellic acids Nanoparticles induces cell death in
Prostate cancer cells. The nanoparticle prepared by controlled nanoprecipitation method
and were characterised by dynamic light scattering, scanning electron microscopy etc.
and it’s in vitro cytotoxicity is assisted by different human cell lines.
Adlin jino nesalin J et al.,20 formulated and evaluated nanoparticles containing Flutamide, which were formulated using chitosan polymer by ionic gelation technique. Nanoparticles of different core: coat ratio were formulated and were subjected for total drug Content, loading efficiency, particle size and in vitro drug release studies.
Objective of the study:
The objective of the study is to develop nanoparticles for anticancer drug:
To design suitable formulation of nanoparticles for anticancer drug.
Characterization of formulated nanoparticle.
Evaluation of developed nanoparticles.
8.1 MATERIALS AND METHODS:
Source of data
National and International journals.
Official Pharmacopoeia
Internet browsing
Helinet
From available literature
From library based books.
8.2. Materials:
Anticancer drug and polymers will be procured from suitable Pharma grade Manufacturer. Other Reagents are of Analytical grade.
Polymers: hydrophilic polymers such as bovine serum albumin, chitosan, and gelatin. Lecitin, legumin and vicillin. Polysaccharides are alginate, dextran, chitosan and pollulan. Collagen, poly methacrylic acid, eudragit, polyvinyl alcohol, etc. From the above mentioned list and any other suitable polymers will be used.
Method of collection of data.
1) Formulation of nanoparticles for an selected anticancer drug by any one of suitable following method.
Solvent emulsification method.
Solvent evaporation method.
Nano/co precipitation method.
Nano encapsulation method
Ionic gelation method, etc.
2) Selection of suitable drug and polymer for the preparation of nanoparticles.
Preformulation studies.
Evaluation of formulated nanoparticles include:
Drug polymer interaction studies.
Drug loading efficiency.
In vitro drug release studies
Release kinetics
Stability studies for selected batches as per ICH guidelines.
3) Physical Characterization
a. Particle size and surface morphology determination
Scanning electron microscopy.
Does the study require any investigation or inventions to be conducted on
Patients or other human or animals? If so, please describe briefly.
No
8.5 Has ethical clearance been obtained from your institution in case of 7.3?
Not applicable.
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Dinarvand R. Polylactide-co-glycoside nanoparticles for controlled delivery of
Anticancer agents. Int. J. of Nanomedicine 2011; 6:877-95.
http://womenhealth.about.com/cs/cancer/a/diagtreatcancer_3.htm.Accessed on 09/11/2010.
Li Zhang & Liangfang Zhang, lipid –polymer hybrid nanoparticle: synthesis,
Characterisation and applications. 2010;1(1&2):163-173.
Mark E. Davis, Zhuo (Georgia) Chen & Dong M. Shin Nanoparticle therapeutics: an
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12) Umasankar.K and Maheswara Reddy.C2. Formulation and evaluation of Cytarabine
Nanoparticles. Int. J. of Innovative Pharm Res, 2010; 1(2):48-52.
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Nilesh M. Mahazan, Dr. Dinesh M.Sakarkar, Amit S. Manmode. Design and
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Vinod Ramani, Sachin Chauhan, Jibin Joshi, Tejas Ghelani, Gajanan Deshmukh.
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Rajat Sharma, Mohd Yasir, Sanjay Bhaskar and Mohd Asif :Formulation and
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Saji Uthaman, Snima K.S, Annapoorna M, Ravindranath K.C, Shanti V, Nair, Vinoth-
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Adlin jino nesalin j, Gowthamarajan K and Somashekhara C.N. Formulation and
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