nanotechnology in tuberculosis

Potential of Nanotechnology as a delivery platform against

Tuberculosis

Guided by:Dr. K.N. Gujar M.Pharm, Ph.D

Co-guided by: DR. M.S. GAMBHIRE

M. Pharm, Ph.D

Presented by:Mr. Aniket A. Vaidya

M. Pharm 1st sem.Pharmaceutics

Roll no. 522

Sinhgad College Of Pharmacy, Vadgaon (BK), Pune-41

A seminar on

Date of seminar: 29 OCT. 2015

1 Aniket A. Vaidya

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Introduction:Tuberculosis is an airborne disease caused by the bacterium Mycobacterium tuberculosis (M. tuberculosis) .mycobacterial species : (M. bovis, M. africanum, M. microti, M. caprae, M. pinnipedii, M. canetti and M. mungi) together comprise what is known as the M. tuberculosis complex. M. tuberculosis organisms are also called tubercle bacilli.

Jung Kwon Oha et al , The development of microgels/nanogels for drug delivery applications, Progress In Polymer Science 33 (2008) 448–477

Mycobacterium tuberculosis

Types of Tuberculosis

Ganga Srinivas et al.” Polymer Based Microgels/Nanogels: Development and Application In Drug Delivery” Am. J. PharmTech Res. 2014; 4(1) ISSN: 2249-3387

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Symptoms and Sings of Tuberculosis

Ganga Srinivas et al.” Polymer Based Microgels/Nanogels: Development and Application In Drug Delivery” American Journal of Pharma Tech .Research. 2014; 4(1) ISSN: 2249-3387

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Pathogenesis of TB

Jung Kwon Oha et al , The development of microgels/nanogels for drug delivery applications, Prog. Polym. Sci. 33 (2008) 448–477

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NANOTECHNOLOGY

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Nanotechnology is the study of extremely small structures, having size of 0.1 to 100 nm

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Routes and mechanisms of particle transport across epithelia

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Nanoparticle transport

Jung Kwon Oha, Ray Drumright et al , “The development of microgels/nanogels for drug delivery applications”, Progress in Polymer Science. 33 (2008) 448–477.

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Objective

Jung Kwon Oha, Ray Drumright et al , “The development of microgels/nanogels for drug delivery applications”, Progress in Polymer Science. 33 (2008) 448–477.

Fig:Reverse micellar method for the preparation of nanogels.

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Jung Kwon Oha, Ray Drumright et al , “The development of microgels/nanogels for drug delivery applications”, Progress in Polymer Science. 33 (2008) 448–477.

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Encapsulation of ATDs into multifunctional polymeric nanoparticles.

Encapsulation of all four drugs

Sanjida Sharmin et al, “ An Overview of Nanogel Drug Delivery System”. Journal of Applied pharmaceutical science vol.3 september 2013.

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PLGA Nanocapsule

Encapsulation of pre-formed drug-loaded micelle-like containers

Pharmaceutical consideration

1. Drug loading:

a. Post formation loadingb . In situ loading

2. Covalent conjugation3. Self assembly

Ganga Srinivas et al.” Polymer Based Microgels/Nanogels: Development and Application In Drug Delivery” American Journal of Pharma Tech .Research. 2014; 4(1) ISSN: 2249-3387

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PROPERTIES

• Biocompatibility and degradability

• Swelling property

• Higher drug loading capacity

• Particle size

• Solubility

• Electromobility

• Colloidal stability

• Others

Sanjida Sharmin et al, “ An Overview of Nanogel Drug Delivery System”. Journal of Applied pharmaceutical science vol.3 september 2013.

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CASE STUDY : 1

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MaterialsChitosanPolylacticacidDichloromethanePolyethylene

glycolGelatinPoly(ethylene

oxide)Phosphate buffer

salineRifampicin

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Methods

Preparation of CS-PLA nanoparticles

Preparation of Rifampicin loaded CS-PLA nanoparticles

Method of preparation

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Aq. Solution of drug + polymer solution

w/o emulsion poured into 10ml of 1% acetic acid solution contain 60mg of CS & 200mg of PEO

Add water , nanoparticles ppt then cooled at 10oC

Mixture sonicate for 60 min Form emulsion

Nanoparticles evaoporated by rotary evaporator

Then the above mentioned procedure was followed and added PEG and gelatin.

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The prepared nanoparticles were named as

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chitosan–polylactic acid encapsulated rifampicin (CS–PLA–RIF),

chitosan–polylactic acid–polyethyleneglycol encapsulated rifampicin (CS–PLA–RIF–PEG)

and chitosan–polylactic acid–polyethylene glycol–gelatin encapsulated rifampicin (CS–PLA–RIF–PEG–G).

Results :

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Fig.The zeta pontential values of CS–PLA–RIF, CS–PLA–RIF–PEG,CS–PLA–RIF–PEG–G with various concentrations.

Particle size and zeta potential of the prepared nanoparticles

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Surface morphology

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Fig. 2. SEM images of rifampicin (a), CS–PLA–RIF (b), CS–PLA–RIF–PEG (c) and CS–PLA–RIF–PEG–G (d).

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FTIR Spectra

Fig. 3. FTIR spectra of CS–PLA–RIF, CS–PLA–RIF–PEG and CS–PLA–RIF–PEG–G (a),and 10–50% of RIF encapsulated CS–PLA–RIF–PEG–G (b).

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In vitro studies

Fig. 4. In vitro analysis of rifampicin prepared nanoparticles.

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Cell inhibition studies

The relative cell viability of RIF, CS–PLA–RIF, CS–PLA–RIF–PEG and CS–PLA–RIF–PEG–G nanoparticles

Conclusions:In this study, the effectiveness of SLN gel for dermal

delivery of MLX was investigated.They seemed appropriate for sustained and controlled

release due to the possible formation of a drug depot in the skin. Thus,

It can be concluded that SLNs offer a better option for the delivery of NSAIDs via skin in order to avoid gastrointestinal side effects which occur after oral administration.

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CASE STUDY : 2

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Materials Poly(lactic-co-glycolic acid) (PLGA)(lactic acid:glycolic acid ratio=75:25) Nanoparticles-containing mannitol (MAN) Rifampicin (RFP) Rat normal alveolar macrophage cells Coumarin 6 Indomycin green (ICG)

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Methods Preparation of RFP-PLGA nanoparticle-containing MAN

microshperes using a four-fluid nozzle spray drier

Preparation of RFP-PLGA microspheres using a

traditional two-fluid spray drier

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Preparation of RFP–PLGA nanoparticles-containing MAN microspheres using a four-fluid nozzle spray drier (model MDL-050)

RFP:PLGA (1:10)

dissolved at 1.67%(w/v) in a 2:1 solution of acetone/methanol

MAN

dissolvedIn water at 16.7% (w/v)

RFP–PLGA:MAN composition ratioof 1:10 (w/w)

29The RFP/MAN micro particles were prepared in the same manner

Spray drying conditions:inlet temperature, 60 °C; supply rate for coumarin–PLGA or MANsolutions, 5 mL/min; spray rate for air, 30 L/min; spray air pressure,0.78 MPa.

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Schematic diagram of the four-fluid nozzle

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Preparation of RFP–PLGA microspheres using a traditional two-fluidspray drier (Pulvis mini-spray GB22)

RFP:PLGA ratio

was 1:10RFP and PLGA were dissolved at 4.4%(w/v) in a 2:1 solution of acetone/methanol

Water was added at 5%v/v in the spray solution

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Spray drying conditions: inlet temperature, 50 °C; supply rate for solution,5mL/min; spray air pressure, 0.29 MPa

Result

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Fig. 1 SEM photographs and images of the RFP/PLGA microspheres, the (RFP/PLGA)/MAN microspheres, and the RFP/PLGA nanoparticles dispersed in MAN.

In-vitro studies

Fig. 2. In vitro uptake percentage of coumarin by alveolar macrophage cells afteradministration of the coumarin/PLGA microspheres and the (coumarin/PLGA)/MANmicrospheres. Dose: 1 μg of coumarin/well. Each point represents the mean±S.D. (n=3).

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Fig. 3. Aerosol performances of RFP/PLGA microspheres and (RFP/PLGA)/MAN microspheres.Each point represents the mean±S.D. (n=3). □, RFP/PLGA microspheres;■, (RFP/PLGA)/MAN microspheres

In-vivo drug release studies

Fig. 5. In vivo uptake of RFP by alveolar macrophages in lungs of rats after administrationof RFP/MAN, RFP/PLGA,and(RFP/PLGA)/MAN microspheres. Dose: 150 μg/kg of RFP.Each point represents the mean±S.E. (n=6).

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Fig 6 In vivo fluorescent images of lungs of rats after administration of ICG/PLGA and (ICG/PLGA)/MAN microspheres

Conclusion

pH responsive chitin-PCL CNGs were developed and a hydrophilic drug,

Dox. was effectively loaded on to the Chitin-PCLCNGs

DTA confirmed the thermal stability of Dox-Chitin-PCL CNGs. swelling

and drug release at acidic pH.

In addition the Dox-Chitin-PCL CNGs shows significant cytotoxic effects

against A549 (lung cancer) cells. These studies prove the potential of

Chitin-PCL CNGs as a promising drug delivery vehicle for lung cancer.

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Conclusion:

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Nanogels are promising and innovative drug delivery system . Nanogels appear to be excellent candidates for brain

delivery .This will be especially important for the targeting of cancer cells.

REFERENCES

1. Jung Kwon Oha, Ray Drumright et al , “The development of microgels/nanogels for drug delivery applications”, Progress in Polymer Science. 33 (2008) 448–477.

2. Sanjida Sharmin et al, “ An Overview of Nanogel Drug Delivery System”. Journal of Applied pharmaceutical science vol.3 september 2013.

3. L.Divya1, V. Ravichandiran et al , “Nanogels – as A Drug Delivery Carrier” , Indo American journal of pharmaceutical research.

4. Reuben T. Chacko, Judy Ventura et al, “Polymer nanogels: A versatile nanoscopic drug delivery platform” , Advanced Drug Delivery Reviews 64 (2012) 836–851.

5. Reuben T. Chacko, Judy Ventura, Jiaming Zhuang, S. Thayumanavan , “Polymer nanogels: A versatile nanoscopic drug delivery platform”, Advanced Drug Delivery Reviews 64 (2012) 836–851.

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6. Dhawal dorwal , “Nanogels as novel versatile pharmaceuticals” , International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 4, Issue 3, 2012

7. Ganga Srinivas, Pooja Ramnathkar, “Polymer Based Microgels/Nanogels: Development and Application In Drug Delivery”, Am. J. PharmTech Res. 2014; 4(1) ISSN: 2249-3387.

8. Farhana Sultana S. Khuranaa, P.M.S. Bedia, N.K. Jainb, “Preparation and evaluation of solid lipid nanoparticles based nanogel for dermal delivery of meloxicam”, Chemistry and Physics of Lipids (2013).

9. T.R. Arunraj, N. Sanoj Rejinold, N. Ashwin Kumar, R. Jayakumar, “ Doxorubicin-chitin-poly (caprolactone) composite nanogel for drug delivery’’ ,International Journal of Biological Macromolecules 62 (2013) 35– 43.

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