DESIGN AND EVALUATION OF FUNCTIONALISED SILVER NANOPARTICLES AS TOPICAL GEL

M.PHARM DISSERTATION PROTOCOL

SUBMITTED TO THE

RAJIVGANDHIUNIVERSITY OF HEALTH SCIENCES,

BANGALORE, KARNATAKA.

By

SWAMY SAHITI

Under the Guidance of

BASAWARAJ BENDEGUMBLE

M.Pharm.,(Ph.D)

DEPARTMENT OFPHARMACEUTICAL TECHNOLOGY

H.K.E.S’s Matoshree Taradevi Rampure Institute of Pharmaceutical Sciences

GULBARGA-585105

2011-2012

RAJIVGANDHIUNIVERSITY OF HEALTH SCIENCES, KARNATAKA

BANGALORE

ANNEXURE-II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1. / Name of the candidate
(in block letters) / SWAMYSAHITI
Permanent Address / SWAMY SAHITI
D/O S. ACHUTA RAO
C/O B. VISHWANADHAM
H.NO. 2-1-288
Opp. POTTI SRIRAMULU STATUE
KHAMMAM
ANDHRA PRADESH
2. / Name of the Institution / HKES’s, Matoshree Taradevi Rampure Institute of Pharmaceutical Sciences, SEDAM ROAD,
GULBARGA-585105
3. / Course of study and subjects / M.PHARM
(PHARMACEUTICAL TECHNOLOGY)
4. / Date of admission to the course / 18-12-2011
5. / Title of the Topic / DESIGN AND EVALUATION OF FUNCTIONALISED SILVER NANOPARTICLES AS TOPICAL GEL
6. /

Brief Resume of the Intended work

6.1 /

Need for the study:

Nanotechnology is the engineering of functional systems at the molecular scale of dimension between 1.0 and 100 nm. This technology is expected to open some new aspects to fight and prevent life threatening lethal diseases. The pace of new, novel discoveries in pharmaceutical and allied fields endeavour in recent years have opened some exciting and challenging time for pharmacists [1].
Since long, different forms of the silver is used in antimicrobial formulations. Way back to the history a German doctor, Crede, applied low concentration of aqueous sliver nitrate solution against blindness in infants. Very popular formulation, silver sulfadiazine topically used as antimicrobial agent to treat different wound and associated infections.
This era witnessed the highest morbidity and mortality in burn wound infections. Burn wounds spontaneously, abnormally disturb the internal defence mechanism of the host and thereby the host skin membranes will invite many toxic, resistant microorganisms leading to sepsis. High vulnerability in invasive pathogens leads to repeated lethal infections if not taken care with respect to complete skin.Dose-dumping and overuse of conventional antibiotics resulted in multidrug-resistant nosocomial pathogens like pseudomonas, epidermidis, mirabilis infections.
The topical antibacterial formulation especially as gel aimed to control the surface microbial proliferation in burn wound care. In this regard we have architected our protocol proposal by designing and evaluating silver nanoparticles (AgNP) as topical gel preparation for wound healing and comparative study is done with respect to commercial preparation.The other regular studies of the gel formulations with respect to irritability, spreadability, viscosity, stability etc[2].
The importance of bactericidal nanomaterial study is because of the increase in new resistant strains of bacteria against most potent antibiotics. This has promoted research in the well-known activity of silver ions and silver based compounds including silver nanoparticles. Especially with silver nanoparticles(AgNP) the toxicity can be marginally reduced after functionalization which is an important parameter while preparing formulation for wound healing. e.g., argyria and delayed wound healing.

6.2

/

Review of Literature:

  • The literature survey was carried out by referring various scientific journals, the facility of internet and helinet. Some of the published reports related to proposed topic are summarized in the following sections.
  • Pople P.V, Singh K.K. They have reported that solid lipid nanoparticles are highly effective, non-irritant carrier for cosmetic and topical preparations SLN also have the potential to localize the drug at the site specific delivery of drug to the skin [3].
  • Tian J, Wong K.K.Y et al. They have studied the new therapeutic modality of silver nanoparticles for the treatment of burn wounds. The results have given an insight action of silver and they have provided a novel therapeutic direction for the treatment of wounds in clinical practice [4].
  • Mishra M, Kumar H, Tripathi K. Studied that silver nanoparticles is novel nanosized and highly crystalline antibacterial agent. The review is an attempt to illustrate the molecular signalling of the apoptosis involved in delayed wound healing and the role of silver nanoparticles in earlier healing. They can be beneficial in delayed diabetic wound healing as diabetic wounds are affected by many secondary infections and also help in early wound healing with minimal scars in diabetic patients [5].
  • Singh M, Singh S, Prasad S et al. They have given the importance of bactericidal nanomaterial study is because of the increase in new resistant strains of bacteria against the most potent antibiotics. This has promoted research in the well-known activity of silver ions and silver based compounds including AgNP[6].
  • Gajbhiye M, kesharwani J et al. Reported the extracellular biosynthesis of silver nanoparticles using a common fungus Alternaria alternata. Fluconazole in combination with AgNP showed the maximum inhibition against C. albicans, followed by P. glomerata and Trichoderma sp and no significant enhancement of activity was found against P. herbarum and F. Semitectum[7].
  • Guzman M, Godet S et al.They have clearly demonstrated that the colloidal silver nanoparticles inhibited the growth and multiplication of the tested bacteria, including highly multi-resistant bacteria such as methicillin resistant Staphylococcus aureus etc such high antibacterial activity were observed at very low total concentration of silver less than 6.74 mcg/ml[8].
  • Mahltig B, Haufe H et al. Have studied about silver nanoparticles embedded in sio2 powder is determined against the bacteria Escherichia coli and Bacillus subtilis and the fact that sio2 microsphere powder exhibits a good dispersibility and such materials have an immense potential to be used as an antimicrobial additive in process like master batch or fiber production[9].
  • Saleem M.A, Bala S. They have concluded that solid dispersion complex incorporated gel shows highest permeation when compared to that of the plain drug gels[10].
  • Darroudi M, Ahmad MB. Synthesized AgNP by UV irradiation of aqueous solutions containing AgNO3 and gelatine as a silver source and stabilizer, respectively. When the irradiation time was increased, the mean size of particles constantly decreased as a result of photo induced AgNP fragmentation. The study reveals that the UV irradiation mediated method is a green chemistry and promising route for the synthesis of stable silver nanoparticles[11].
  • Mallikarjuna K, Narasimha G et al .They have developed silver nanoparticles using leaf broth of Ocimum sanctum and concluded that they have potential applications in the biochemical field and this simple procedure has several advantages for medical and pharmaceutical applications[12].
  • Neubert R.H.H. The primary goal of his studies is to develop new nanocarriers and to overcome this protective and effective barrier’s like stratum cornium(sc) for that reason development of new nanocarriers such as micro-emulsions, vesicular (liposomes) and nanoparticular nanocarriers have been developed and investigated. The ultimate aim is to understand the interactions between stratum corneum lipid membrane and different dermal and transdermal nanocarriers[13].
  • Prow T.W et al.Studied about how the skin provides a natural physical barrier against particle penetration, but there are many opportunities to deliver therapeutic nanoparticles especially in diseased skin[14].

6.3 /

Objectives of the study:

  • Since centuries silver is famous for its antibacterial, anti-inflammatory and wound healing effects.
  • It also quite established that the different forms of the silver including AgNP are proved to be very effective antibacterial and wound healing materials.
  • Looking on to the efficacy and safety profiles of functionalised silver nanoparticles we have planned to design and develop AgNP using ‘green-clean’ chemistry techniques and characterize using newer spectroscopic and microscopic techniques.
  • Optimize them for making highly biocompatible ones and further formulated as in clear gel form. The biologically designed and developed AgNP will be characterized by UV-Vis absorption spectroscopy, FT-IR and SEM, TEM and AFM techniques.
  • In the proposed research, we are aiming to prepare functionalizedAgNPin gel formulation for topical drug delivery these AgNP are biosynthesised using different plant extracts.
  • The work is further extended for studying the therapeutic efficacy of silver nanoparticles as anti-bacterial agent in topical drug delivery system and comparative studies will be done with respect to marketed preparations.
  • The formulated gel will be evaluated for various parameters like their size, shape, viscosity, pH, sterility, drug content uniformity and In-vitro drug release studies. AgNP are prepared using green synthesis method and formulated with the gelling systems prepared with Carbopols and other polymers.

7 / Materials and Methods:
7.1 /

Source of data:

  • Internet
  • Helinet facility of our affiliating universityRGUHS Bangalore.
  • International pharmaceutical journals.
  • National pharmaceutical journals.

7.2 / Materials:
  • Drug- Silver nanoparticles
  • Polymers- Carbopol (934p, 971p, 940P& 974p), and others.
  • Viscolysers- Hydroxy propyl methyl cellulose( HPMC), Chitosan, Methyl cellulose( MC), Sodium carboxy methyl cellulose(Sod. CMC) etc.
  • Preservatives- Benzalkonium chloride, Methyl paraben and propyl paraben.
  • Surfactants/emulsifier- Triethanolamine
  • Humectants- Glycerine, Glycerol, propylene glycol
  • Other chemicals- Silver nitrate, Silver sulphadiazine, Ciprofloxin, Reducing agents etc.

Equipments :
  • UV-visible spectrophotometer (shimadhu 1700).
  • Digital pH- meter (Elico LI 122).
  • Brook field viscometer.
  • Diffusion test apparatus.
  • Magnetic stirrer (Remi Equipment, Mumbai).
  • Single pan electronic balance.
  • Hot air oven.
  • Thermostatic hot plate with magnetic stirrer.
  • Zeta potential analyzer.
  • Microwave
Advanced microscopic techniques like:
  • AFM- Atomic force microscopy.
  • TEM- Transmission electron microscopy.
  • FESEM-Field emission scanning electron microscopy.
  • SEM- Scanning electron microscopy

7.3 / Method:
The AgNP is synthesized by treating the aqueous10-3N AgNO3solutions reduced with aqueous sandal wood extract similar to procedures as reported in our earlier research papers.
Evaluation of silver nanoparticles embedded gel :
The silver nanoparticles embedded gel system will be evaluated for:
  • pH
  • Viscosity
  • Drug content uniformity
  • Size, Shape and Entrapment efficiency
  • In vitro release study
  • Test for sterility and
  • In vitro antimicrobial activity,
  • Drug leakage on storage and stability.
  • Wound healing studies
  • Skin irritation
  • Spreadability

7.4 /

Does the study require any investigation or intervention to be conducted on patients or other humans or animals? If so please describe briefly

…………………… Applied ……………………

7.5 /

Has ethical clearance have been obtained from your institution in case of 7.3?

………………………Yes …………………………

8. /

List of References:

  1. Bhowmik D, Chiranjib, et al. Role of Nanotechnology In Novel Drug Delivery System. Journal of Pharmaceutical Sciences and Technology 2009; 1(1): 20-35.
  2. Rai R.V, Bai J.A (2011), nanoparticles and their potential applications as antimicrobials. A Mendez Vilas, Science against microbial pathogens: communicating current reaserch and technological advances. Formatex. P.197-209.
  3. Pople P.V, Singh K.K. Development and Evaluation of Topical Formulation Containing Solid Lipid Nanoparticles of Vitamin A. AAPS PharmSciTech 2006; 7(4), 1-7.
  4. Tian J, Wong K.K.Y, Tam P.K.H, et al. Topical Delivery of Silver Nanoparticles Promotes Wound Healing. ChemMedChem 2007; 2: 129-36.
  5. Mishra M, Kumar H, Tripathi K. Diabetic Deladed Wound Healing And The Role Of Silver Nanoparticles. Digest Journal of Nanomaterial and Biostructures 2008; 3(2): 49-54.
  6. Singh M, Singh S, Prasad S, Gambhir I.S. Nanotechnology In Medicine And Antibacterial Effect Of Silver Nanoparticles. Digest Journal of Nanomaterials and Biostructures 2008; 3(3): 115-22.
  7. Gajbhiye M, Rai M, et al. Fungus-medicated synthesis of silver nanoparticles and their activity against pathogenic fungi in combination with fluconazole. Nanomedicine: NBM 2009; 5: 382-86.
  8. Guzman M.G, Dille J, Godet S. Synthesis of silver nanoparticles by chemical reduction method and their antibacterial activity. International Journal of Chemicals and Biological Engineering 2009; 2(3), 104-111.
  9. Mahltig B, Haufe H, Muschter K, Fischer A, Kim Y.H, Gutmann E, et al. Silver nanoparticles in SiO2 Microspheres-Preparation by Spray Drying and Use as Antimicrobial Agents. Acta Chim. Slov. 2010; 57: 451-57.
  1. Saleem M.A, Bala S. Formulation And Evaluation Of Meloxicam Solid Dispersion Incorporated Topical Gels. International Journal of Pharma and Bio Sciences 2010; 1(3), 1-9.
  2. Darroudi M, Ahmad M.B, et al. Fabrication and Charecterization of Gelatin Stabilized Silver Nanoparticles under UV-Light. Int. J. Mol. Sci. 2011; 12: 6346-56.
  3. Mallikarjuna K, Raju B.D.P, Narasimha G, Praveen B, et al. Green Synthesis Of Silver Nanoparticles Using Ocimum Leaf Extrct And Their Charecterization. Design Journal of Nanomaterials and Biostructures 2011; 6(1): 181-86.
  4. Neubert R.H.H. Potentials of new nanocarriers for dermal and transdermal drug delivery. European Journal of Pharmaceutics and Biopharmaceutic 2011; 77: 1-2.
  5. Prow T.W, Grice J.E, Lin L.L, Roberts M.S, et al. Nanoparticles And Microparticles For Skin Drug Delivery. Advanced Drug Delivery Reviews 2011; 63: 470-91.
  6. Biosynthesis of Polyshaped Gold Nanoparticles from guava leaf extractPublished in Nanobiotechnology, Springer,2009, 5, 1-4, 34-41. IF: 4.9
  7. Biosynthesis of Irregular Gold Nanoparticles from dried clove buds.Colloids and surfaces B: Biointerfaces,Elsevier, 79, 1(1) 2010, Pages 235-240. IF: 3.00
  8. Biosynthesis of silver nanoparticles using guava leaf extract.Journal of Nanoparticle Research, Springer, doi: 10.1007/s11051-010-9956-8O.3.3
  9. Anti-cancer studies of noble metal nanoparticles synthesized using different plant extracts,cancer nanotechnology, Springer doi:10.1007/s12645-011-0014-8 IF: Awaited
  10. Preparation andcharacterization ofpolypyrrole silvernano-composites viaInterfacial Polymerization.International Journal of Polymeric Materials, Taylor & Francis Group. 59:531–543, 2010. doi: 10.1080/ 00914031003760642. IF:0.5

9. / Signatures of candidate / [Ms. SWAMY SAHITI]
10. / Remarks of Guide / The worked proposed is novel one, we can formulate more efficacious delivery system. The proposed was neither published nor reported anywhere, so recommended for registration.
11. / Name and designation of
(in block letters)
11.1 Guide / BASAWARAJ BENDEGUMBLE
M. Pharm.,(Ph.D)
LECTURER
DEPT.OF PHARMACEUTICAL TECHNOLOGY
H.K.E.S’s MATOSHREE TARADEVI RAMPURE INSTITUTE OF PHARMACEUTICAL SCIENCES, GULBARGA-585105.
11.2 Signature
11.3 Co-guide / Dr. RAGHUNANDAN DESHPANDEM.Pharm., Ph.D
PROFESSOR
DEPT.OF PHARMACEUTICAL TECHNOLOGY
H.K.E.S’s MATOSHREE TARADEVI RAMPURE INSTITUTE OF PHARMACEUTICAL SCIENCES,
GULBARGA-585105.
11.4 Signature
11.5 Head of the Department / Dr.K.PURUSHOTAM RAO
M. Pharm., Ph.D
PROFESSOR INCHARGE AND H.O.D
DEPT.OF PHARMACEUTICAL TECHNOLOGY
H.K.E.S’s MATOSHREE TARADEVI RAMPURE INSTITUTE OF PHARMACEUTICAL SCIENCES,GULBARGA-585105.
11.6 Signature
12 / 12.1 Remarks of chairman and Principal
12.2 Signature

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