Nanosponge: Targeted Drug Delivery System

Presented by, Rasika.WalunjM.Pharm (QAT)

Modern College Of Pharmacy (For Ladies) Moshi Pune 412105

Content

1. Aim and objective 2. Introduction 3. What is Nanosponges ? 4. Advantages 5. Disadvantages6. Chemical used for the synthesis of Nanosponges7. Method of preparation8. Evaluations of Nano sponges

Aim : To review and study Nanosponge as a novel& targeted drug delivery system

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

Introduction 1. Effective targeted drug delivery systems have been a dream for long

time. 2. The invention of Nano sponges has become a significant step towards

overcoming these problems. 3. These small sponges can circulate around the body until they encounter

the target site and stick on the surface and began to release the drug in a controlled and predictable manner which is more effective for a particular given dosage.

4. Owing to their small size and porous nature they can bind poorly-soluble drugs within their matrix and improve their bioavailability.

5. They can be crafted for targeting drugs to specific site, prevent drug and protein degradation and prolong the drug release in a controlled manner.

6. This presentation attempts to elaborate the interesting features of Nano sponges, preparation, Characterization, applications and recent updates of Nano sponges in drug delivery.

What is Nanosponges…??

What is Nanosponge..??

1. Nanosponges are tiny sponges with a size of about a virus with an average diameter below 1μm.

2. The sponge acts as a three-dimensional network or scaffold, which consist of the backbone known as long-length polyester.

3. Filling them with a “drug” and attaching special chemical “linker” this tiny sponges circulating around body until they encounter a targeted site.

4. The Nanosponges are solid in nature and can be formulated as oral, parenteral, topical or inhalational dosage forms.

5. Nanosponge is a novel and emerging technology which play a vital role in targeting drug delivery in a controlled manner

Advantages This technology provide entrapment of active contents and

side effects are less. It provides improved stability, elegance and formulation

flexibility. It is non-mutagenic. Non-irritating, non-toxic. It provide extended release condition which is continuous

action up to 12hr. Drug is protected from degradation. Therapeutic provide onset of action. Formulations are cost effective.

Advantages It can be used to mask unpleasant flavours 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 encapsulation can be done within the Nanosponge, by the addition of chemical called an adjuvant reagent.

Particles can be made smaller or larger by varying the proportion of cross-linker to polymer.

Easy scale-up for commercial production. The drug profiles can be vary from fast, medium to slow release

in case of dosing therapy. Predictable release. Biodegradable

Disadvantages

Nanosponges include only small molecules.Depend only upon loading capacitiesDose dumping may take place. May retard the release

Chemical used for the synthesis of Nanosponges

• Polymers1. Hyper cross linked Polystyrenes,

Cyclodextrines and its derivatives like Methyl β- Cyclodextrin.

2. Alkyloxycarbonyl Cyclodextrins, 2-Hydroxy Propyl β- Cyclodextrins and copolymers like Poly( valerolactone-allylvalerolactone and Ethyl cellulose & PVA

Chemical used for the synthesis of Nanosponges

• Cross linkers :1. Diphenyl Carbonate, Diarylcarbonates,

Carbonyldiimidazole,Epichloridine Glutarldehyde, Carboxylic

2. Acid dianhydride, Acetic acid and Dichloromethane.

Method of preparation

1. Nanosponges prepared from hyper-cross linked β-cyclodextrins

2. Emulsion solvent diffusion method3. Quasi-emulsion solvent diffusion4. Ultrasound assisted synthesis

1. Nanosponges prepared from hyper-cross linked β-cyclodextrin

1. In this method, the cross linker is melted along with CDs. All ingredients are finely homogenized and placed in a 250 ml flask heated at 100 °C and the reaction is carried out for 5 hrs. under magnetic stirring.

2. The reaction mixture is allowed to cool and the obtained product is broken down followed by repeated washing with suitable solvents to remove unreacted excipients and by products .

3. The reaction is carried out at temperatures ranging from 10 °C to the reflux temperature of the solvent, for 1 to 48 hrs.

4. Preferred cross linkers for this reaction are the carbonyl compounds diphenyl carbonate , dimethyl carbonate or carbonyl di imidazole

5. The product is obtained by adding the cooled solution to a large excess of bidistilled water. Recovery of the product is done by filtration under vacuum and the product is further purified by prolonged Soxhlet extraction

2.Emulsion solvent diffusion method

1. Nanosponges prepared by using different proportion of ethyl cellulose and polyvinyl alcohol.

2. The dispersed phase containing ethyl cellulose and drug was dissolved in 20ml dichloromethane and slowly added to a definite amount of polyvinyl alcohol in 150ml of aqueous continuous phase.

3. The reaction mixture was stirred at 1000rpm for 2 hrs. 4. The Nanosponges formed were collected by filtration and

dried in oven at 400 c for 24 hrs.5. The dried Nanosponges were stored in vacuum desiccators to

ensure the removal of residual solvent

3.Quasi-emulsion solvent diffusion

1. The Nanosponges prepared using the polymer in different amounts.

2. The inner phase is prepared using eudragitrs 100 and added to a suitable solvent.

3. Drug used provided with a solution and dissolved under ultra sonication at 35ºc .

4. This inner phase added into external phase containing PVA act as emulsifying agent.

5. The mixture is stirred at 1000-2000 rpm for 3hr at room temperature and dried in an air-heated oven at 40ºc for 12hr.

4. Ultrasound assisted synthesis

1. Nanosponges are obtained by reacting polymer with cross linkers without adding or without using solvent and sonication is maintained.

2. The size obtained by this technique will be spherical and uniform. The polymer is mix with a cross linkers in a balanced ratio in a flask.

3. The flask is placed in a molar ratio in an ultrasound bath field with water and temperature maintained at 90ºc. the mixture is sonicated for 5hr.

4. Then the mixture is kept to cool and product is break roughly then the product is washed with water to remove non-reacted polymer and subsequently purified by soxhlet extraction with ethanol.

5. The product is dried under vacuum at 25ºc until its further use is utilized.

Evaluation of Nanosponges

1) Particle size determination: Particle size analysis of loaded and unloaded Nano sponges

performed by laser light diffractometry or Malvern zeta seizer.

Cumulative graph is maintained or ploted as particle size against time to study effect of particle size on drug release.

Particles size greater then 30m impart gritty feeling and particles of sizes between 10 and 25 m preferred and used in final optical formulation.

Evaluation of Nanosponges2) Morphology and surface topography:For preparation of Nano sponges in terms of morphology they are coated with gold-palladium under an atmosphere of orgon at room temperature and surface structure studied by scanning electron microscopy.3) Determination of loading efficiency:Loading efficiency= × 1004) Production yield :Production yield= × 100

Evaluation of Nanosponges5) Dissolution tests:• Dissolution profile of Nanosponges are studied using dissolution

apparatus USP having a modified basket consist of 5ml stainless steel mesh with a speed of rotation around 150 rpm.

• Proper dissolution medium is selected and solubility of active contents are considered to ensure sink conditions. Proper analytical method are used for the sample form dissolution medium.

6) Zeta potential • Zeta potential of any system under investigation is a measure of

the surface charge.7) 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.

Evaluation of Nanosponges8) Fourier transform-infrared spectroscopy:• It serves as a major tool to determine the presence of functional

groups.9) Powder X-ray diffraction (P-XRD) :• 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.

10) Thermo gravimetric analysis (TGA):• These studies are carried out to understand the melting point,

thermo stability and crystalline behaviour of the particle

Evaluation of Nanosponges11) Swelling and water uptake :• % Swelling = × 100

• % Water uptake= × 100 12) Drug release kinetics (In vitro diffusion model) :• 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. The amount of drug in the medium is determined by a suitable analytical method and drug release is calculated to determine the release pattern.

Application 1) Nanosponges as chemical sensors: Nanosponges which are the

type of “ metal oxides” act as a chemical sensors which is used in highly sensitive detection of hydrogen using nanosponge titania. Nanosponge structure initially have no point of contact so there is less hinderance to electron transport and it results in higher 3D interconnect nanosponges titania which is sensitive to H2 gas.

2) Oxygen Delivery System :Characterized by using α, β and ϒ cyclodextrins and this are suspended in water and get saturated with water. A silicone form of membrane can also be used for oxygen permeation with the help of nanosponge/ hydrogel system. They can also applied it to hypoxic tissues caused in various type of diseases.

3) Biomedical applications Nanosponge can be used for contaminated water. Nanosponge have been used for the removal of organic impurities in water

Application 4) Nanosponges as a carrier for biocatalysts and release of enzymes, proteins, vaccines and antibodies :It includes the process applied in industry which correlate with operational condition. Reactions which are not specific give rise to low yields and require high temperatures and pressures which consume large amount of energy and cooling water in down-stream process. This are the drawbacks can be removed by using enzymes as biocatalysts as this operate under high reaction speed, mild condition.5) Solubility enhancement:β-cyclodextrin based nanosponges of itraconazole have enhance solubility of poorly soluble drug. The solubility increased by 50 folds compared to ternary dispersion system. Eg- copolyvidonum.

Application6)Topical agents Nanosponge delivery system is a unique technology for the controlled release of topical agents of prolonged drug release and retention of drug form on skin. 7) Antiviral application:• Nanosponges used in nasal, pulmonary route of

administration. It provide specificity to deliver antiviral drug on RNA to lungs or nasal route through nanocarriers for targeting virus which may cause infection to RTI such as influenza virus, rhinovirus.

• Drugs used as nanocarrriers are- Zidovudine, Saquinavir.

Conclusion 1. From the above study it is concluded that

nanosponges include lipophilic or hydrophilic drugs and release drug at target site in controlled manner.

2. Polymer and cross-linker ratio can be balanced and release rate can be modified.

3. Nanosponges permit the insoluble drugs and prevent the physiochemical degradation of active contents and controlled release.

4. Their small size and spherical shaped had provided nanosponges to develop as different dosage forms like parenteral, aerosol, topical, tablets and capsules.