The document discusses nanosponges as a novel drug delivery system. Nanosponges are porous polymeric nanoparticles that can encapsulate drugs and release them in a controlled manner. They are synthesized using polymers and crosslinkers. Nanosponges have advantages like improved drug stability and bioavailability. Characterization techniques like particle size analysis, SEM, and drug release kinetics are used to evaluate nanosponges. Nanosponges find applications in solubility enhancement, topical products, and as carriers for enzymes, vaccines and antibodies.

1. Presented by,
Rasika.Walunj
M.Pharm (QAT)
Modern College Of Pharmacy (For Ladies)
Moshi Pune 412105

2. Content
1. Aim and objective
2. Introduction
3. What is Nanosponges ?
4. Advantages
5. Disadvantages
6. Chemical used for the synthesis of
Nanosponges
7. Method of preparation
8. Evaluations of Nano sponges

3. Aim : To review and study Nanosponge as a
novel& targeted drug delivery system
Objective
To discuss Nanosponges with their...
Advantages & disadvantages,
Factors influencing there formation,
Method of preparation,
Characterization, and
Applications.

4. 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.

5. What is Nanosponges…??

6. 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

7. 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.

8. 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

9. Disadvantages
Nanosponges include only small molecules.
Depend only upon loading capacities
Dose dumping may take place.
May retard the release

10. Chemical used for the synthesis of
Nanosponges
• Polymers
1. 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

11. Chemical used for the synthesis of
Nanosponges
• Cross linkers :
1. Diphenyl Carbonate, Diarylcarbonates,
Carbonyldiimidazole,Epichloridine
Glutarldehyde, Carboxylic
2. Acid dianhydride, Acetic acid and
Dichloromethane.

12. Method of preparation
1. Nanosponges prepared from hyper-cross
linked β-cyclodextrins
2. Emulsion solvent diffusion method
3. Quasi-emulsion solvent diffusion
4. Ultrasound assisted synthesis

13. 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

14. 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

15. 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.

16. 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.

17. 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.

18. Evaluation of Nanosponges
2) 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=
Actual drug content in nanosponge
Theoretical drug content
× 100
4) Production yield :
Production yield=
Practical mass of nanosponge
Theoretical mass(drug+polymer)
× 100

19. Evaluation of Nanosponges
5) 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.

20. Evaluation of Nanosponges
8) 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

21. Evaluation of Nanosponges
11) Swelling and water uptake :
• % Swelling =
Marking of cylinder at aspecified time point
Initial marking before soaking
× 100
• % Water uptake=
Mass of hydrogel after 72 hrs
hrsInitial mass of dry polymer
× 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.

22. 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

23. 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.

24. Application
6)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.

25. 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.