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Presented By

Patel Bindiya Ramesh

M.Pharm – (I semister)

(Pharmaceutics)

Under the guidance of

Dr. K. H. Ramteke

(M.Pharm, Ph.D.)

Dept. of Pharmaceutics

PE Society’sModern college of pharmacy (for ladies), Moshi,

Pune.

NANOSPONGEA BOON TO THE TARGETED DRUG DELIVERY SYSTEM

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Aim & objective

What is nano sponge ?

Introduction

Advantages

Disadvantages

Factors influencing the formation of nanosponges

Method of preparation

Evaluation of nanosponges

Literature survey

Application

Conclusion

Referencea

Contents...

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AIM : To review and study nanosponge as a novel & targeted drug delivery system.

To discuss nanosponges with their... Advantages & disadvantages,Factors influencing there formation, Method of preparation, Characterization, and Applications.

OBJECTIVE

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Nanosponges are tiny sponges with a size of about a virus

(250nm – 1μm), which consist of cavities that can be filled with

a wide variety of drugs.

The sponge acts as a three-dimensional network or scaffold, which

consist of the backbone known as long-length polyester.

It is mixed in solution with cross-linkers to form the polymer.

What Is Nano Sponge ???

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Targeting the drug delivery has long been a problem for medical

researchers how to get them to the right place in the body and how

to control the release of the drug to prevent overdose.

The development of new and complex molecules called

Nanosponges has the potential to solve these problems.

Nanosponge is a novel and emerging technology which play a vital

role in targeting drug delivery in a controlled manner.

Nanosponges are a new class of materials and made of microscopic

particles with few nanometres wide cavities in which a large variety

of substances can be encapsulated.

Introduction

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A wide variety of drugs can be loaded into nanosponge for targeting drug

delivery.

These particles are capable of carrying both lipophilic and hydrophilic

substances and of improving the solubility of poorly water soluble

molecule.

Nanosponges are tiny mesh like structures is about the size of a virus

with a backbone of naturally degradable polyester.

They cross link segments of the polyester to form

a spherical shape that has many pockets / cavities where

drug can be stored.

Cont…

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The nanoscale materials are small enough to be effective in attaching to or passing

through cell membranes.

The polyester is biodegradable, so it breaks down gradually in the body & releases

its drug payload in a predictable fashion.

These tiny sponges can circulate around the body until they encounter the specific

target site and stick on the surface and begin to release the drug .

As compared to other nanoparticles, nanosponges are porous, non toxic and

stable at high temperatures up to 300oC.

Cont …

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The nanosponges are solid in nature and can be formulated as oral,

parenteral, topical or inhalational dosage forms.

For oral administration, these may be dispersed in a matrix of excipients,

diluents, lubricants which is suitable for the preparation of tablets or

capsules.

For parenteral administration, these can be simply mixed with sterile

water, saline or other aqueous solutions.

For topical administration, they can be

effectively incorporated into topical

hydro gel.

Cont…

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Targeted site specific drug delivery.

Can be used to mask unpleasant flavours, odour and to convert liquid

substances to solids.

Less harmful side effects (since smaller quantities of the drug have

contact with healthy tissue).

Nanosponge particles are soluble in water, so the hydrophobic drugs can

be encapsulated within the nanosponge, after mixing with a chemical

called an adjuvant reagent.

Particles can be made smaller or larger by varying the proportion of

cross-linker to polymer.

Advantages of Nanosponges

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Biodegradable.

Nanosponge formulations are stable over range of ph 1 to 11.

Nanosponge formulations are stable at the temperature up to 130˚c

These formulations are compatible with most vehicles and ingredients.

These are self sterilizing as their average pore size is 0.25μm where

bacteria cannot penetrate.

These formulations are free flowing and can be cost effective

Improved stability, increased elegance and enhanced formulation flexibility.

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The main disadvantage of these nanosponges is their ability to include

only small molecules.

Dose dumping may take place.

May retard the release.

Materials Used For Preparation Of Nanosponges

DISADVANTAGE

Polymers : Hyper cross linked polystyrenes, ethyl cellulose, 2- hydroxy proply β – cyclodextrins, poly valerolactone, Eudragit RS 100, acrylic polymers

Cross linkers : Dichloromethane, diphenyl carbonate, acrylamido, glutarldehyde, Carboxylic acid dianhydride ,

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Type of polymer : Type of polymer used can influence the formation as well

as the performance of Nanosponges. For complexation, the cavity size of

nanosponge should be suitable to accommodate a drug molecule of particular

size.

Type of drugs : Molecules to be complexed with nanosponges should have

certain characteristics mentioned below

1. Molecular weight between 100 – 400 Da .

2. Drug molecule consists of less than five condensed rings .

3. Solubility in water is less than 10mg/mL .

4. Melting point of the substance is below 250°C.

Factors influencing the formation of nanosponges

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Temperature : Increasing in the temperature decreases the stability of

the drug/nanosponge complex, may be due to a result of possible

reduction of drug/nanosponge interaction forces.

Method of preparation : The method of loading the drug into the

nanosponge can affect Drug/Nanosponge complexation.

Degree of substitution : The complexation ability of the nanosponge

may be greatly affected by type, number and position of the substituent

on the parent molecule.

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1 • Polymer is mixed with a suitable solvent like polar aprotic solvent.

2• This mixture is added to excess quantity of

the cross-linker preferably in cross-linker/polymer molar ratio of 1:4.

3• Action is carried out at temperature

ranging from 10°C to the reflux temperature of the solvent, for time ranging from 1 to 48 hr

4• After completion of the reaction, the solution

is cooled at room temperature and the product is added to large excess of distilled water.

5 • The recovery of the product is done by filtration under vacuum.

METHOD OF PREPARATION

1. Solvent method

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Nanosponges are obtained by reacting cyclodextrin with a cross-

linker such as di isocianates, diaryl carbonates, dimethyl

carbonate, diphenyl carbonate, and carbonyl diimidazoles.

The average diameter of a Nanosponge is below 1 µm but

fractions below 500 nm can be selected.

2. Hyper Cross- Linked β- Cyclodextrins

CYCLODEXTR

IN

CROSS-LINKER

IN SOLVENT

NANOSPONGE

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• In this method, nanosponges can be obtained by reacting polymers

with cross-linkers in the absence of solvent and under sonication.

• The nanosponges obtained by this method will be spherical and

uniform in size.

4. Ultrasound-Assisted synthesis

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Organic internal phase containing drug & polymer in solvent is added to

External phase containing emulsifying agent

Than mixture is stirred at 1000-2000 rpm for 3 hrs at RT

Formed nanosponge were filtered, washed & dried at RT

3. Emulsion Solvent Diffusion Method

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Suspend the nanosponges in

water and sonicate to avoid the

presence of aggregates

then centrifuge the suspension to

obtain the colloidal fraction

Prepare aqueous

suspension of

Nanosponge and

disperse the excess amount of the drug

and maintain

the suspension

under constant

stirring at specific time for

complexation

Nanosponges

Loading Of Drug Into Nanosponges

After complexation, separate the uncomplexed

(undissolved) drug by centrifugation

Then obtain the solid crystals of nanosponges

by

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Author Aim Method used Result

CH.N.V. Raja*, G.

Kiran kumar,

Kotapati anusha

Fabrication And Evaluation Of

Ciprofloxacin Loaded Nanosponges For Sustained Release

Solvent method

Formulated NS loaded with Ciprofloxacin antibiotic resulted in sustained release. Among all batches (F5) is considered as the best entrapped (90.80%) NS with greater % drug release (99.4%).

Roberta Cavalli, Ansari Khalid Akhter, Agnese Bisazza

Nano sponge formulation as oxygen

delivery system

Hyper Cross- Linked β-

Cyclodextrins

NS were able to encapsulate, store & release oxygen for prolonged time. US enhanced release & permeation of oxygen. NS is suitable carrier & act as oxygen reservior.

Literature surveys

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Author Aim Method used Result

E. K. PATEL* and RJ. OSWAL

Nanosponge for delivery of calcium in hyperphosphatemia

Hyper Cross- Linked β- Cyclodextrins

SEM – roughly spherical shape, porous in nature & mean particle size - 400nm. zeta potential is high enough. encapsulation efficiencies – 81 – 95 %

Renuka Sharma , Roderick B. Walker and Kamla Pathak *

Evaluation of the Kinetics and Mechanism of Drug Release from Econazole nitrate Nanosponge Loaded Carbapol Hydrogel

Emulsion solvent method

A sustain release topical DDS of econazole nitrate developed as o NS hydro gel offered solubilising matrix for poorly soluble drug. Served as a local depot for sustain drug release.

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Particle Size Determination : Particle size can be determined by laser light diffractometry or Zeta seizer.

Loading Efficiency : The loading efficiency (%) of Nanosponge can be determined by,

Actual drug content

Loading Efficiency = ---------------------------------- X 100

Theoretical drug content

EVALUATION OF NANOSPONGES

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UV spectroscopy is used to carry out the saturated solution interaction

study.

Increasing concentrations of nanosponge solutions (1– 80 ppm) are added

to fixed concentrations of the drug.

The samples are kept overnight for interaction and finally filtered solutions

are scanned for λmax and absorbance is measured.

Drug loading is interpreted by taking scans of the formulation in the UV

range and analyzing the shift of the absorbance maxima in the spectra

compared to pure drug.

• Saturation state interaction

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Bulk volume – True volume

% Porosity (E) = ------------------------------------------ x 100

Bulk volume

Zeta potential :

Zeta potential of any system under investigation is a measure of the surface charge.

SEM and TEM :

These tools are employed to evaluate the particle shape and size and to get morphological information related to the drug delivery system

Fourier transform-infrared spectroscopy (FTIR) :

It serves as a major tool to determine the presence of functional groups.

Porosity : Percent porosity is given by equation

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Diffraction peaks for a mixture of compounds are useful in

determining chemical decomposition and complex formation.

Complex formation of the drug with nanosponges alters the

diffraction patterns and also changes the crystalline nature of

the drug.

Thermo gravimetric analysis (TGA)

These studies are carried out to understand the melting point, thermo

stability and crystalline behaviour of the particle.

Powder X-ray diffraction (P-XRD)

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Marking of the cylinder at a specified

time point

Percentage of swelling = -----------------------------------------------------x 100

Initial marking before soaking

Mass of the hydro gel after 72 hrs

Percentage of water uptake = -----------------------------------------------x 100

Initial Mass of dry polymer

Swelling and water uptake

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• In vitro release kinetics experiments are performed using a multi-

compartment rotating cell; an aqueous dispersion of nanosponges (1

mL) containing the drug is placed in the donor compartment, while the

receptor compartment, separated by a hydrophilic dialysis membrane,

is filled with phosphate buffer at pH 7.4 or pH 1.2.

• Each experiment is carried out for 24 h.

• At fixed times, the receptor buffer is completely withdrawn and replaced

with fresh buffer. The amount of drug in the medium is determined by a

suitable analytical method and drug release is calculated to determine

the release pattern.

Drug release kineticsIn vitro diffusion model

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Spontaneous.

Carcinogen-induced.

Gems (genetically engineered mouse models).

–transgenic

–knockout

–regulatable transgenic

CELL LINES

HT-29 cell line

MCF-7 cell line

In vivo models

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Spontaneous model

Some strains of laboratory animals are susceptible to spontaneously developing certain types of tumor.

Advantagesmay mimic some types of human diseasescan use to study early disease.can use for prevention.includes elements of progression

DisadvantagesVariability of disease progression.Large animal numbers needed.Long time to develop disease.penetrance (not all animals get disease).

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Marketed preparation

Paclitaxel, camptothecin, tamoxifen, econazole nitrate, peroxidase

Drug Administration route

Trade name Market

Dexamethasone Dermal Glymesason Japan

Iodine Topical Mena-gargle Japan

Alprostadil I.V Prostavastin Europe, Japan, USA

Piroxicam Oral Brexin Europe

Temoxifen Oral - -

Other examples patented drugs used in nanosponge preparation

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Cancer.

Oxygen delivery systems.

As a carrier for biocatalysts and in the delivery

and release of enzymes, proteins, vaccines and antibodies.

Harvesting of rare Cancer Marker from Blood.

Solubility enhancement.

Topical drug delivery system.

Antiviral application.

More effectiveness than direct injection.

APPLICATION

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The nanosponges have the ability to include either lipophilic or

hydrophilic drugs and release them in a controlled and predictable

manner at the target site. By controlling the ratio of polymer to the cross-

linker the particle size and release rate can be modulated. Nanosponges

enable the insoluble drugs and protect the active moieties from

physicochemical degradation and controlled release. Because of their

small size and spherical shape nanosponges can be developed as different

dosage forms like parenteral, aerosol, topical, tablets and capsules.

Thus, the nanosponge drug delivery system is a boon in the area of

targeted and site specific drug delivery system.

CONCLUSION

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REFERENCES

G. Yadav., H. Panchory., Nanosponge: A Boon To The Targeted Drug Delivery System, Journal Of Drug Delivery And Therapeutics; 2013, Volume 3(4), Pg. No. 151-155.

F. Trotta., R. Cavalli., Characterization And Applications Of New Hyper Cross - Linked Cyclodextrin, Composite Interfaces, 2009, Volume 16, Pg. No. 39-48.

G. Jilsha., Vidya Viswanad., Nanosponges: A Novel Approach Of Drug Delivery System; Int. J. Pharm. Sci. Rev. 2013 Res Volume 19 (2), Pg. No.119-123.

C. U. Shah, Cyclodextrin Based Nanosponges For Pharmaceutical Use: A Review; Acta Pharm. 2013, Volume 63, Pg. No. 335-358.

S.P. Vyas, R.K. Khar. Targeted And Controlled Drug Delivery- Novel Carrier Systems. Molecular Basis Of Targeted Drug Delivery. Cbs Publishers And Distributors. New Delhi. 2008: Pg. No. 38- 40.

S. Subramanian, A. Singireddy., Nanosponges: A Novel Class Of Drug Delivery System; J Pharm Pharmaceut Sci: 2012, Volume 15(1), Pg. No. 103-111.

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