Nanosponge: An overview
Published on: Mar 3, 2016
Transcripts - Nanosponge
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
It is mixed in solution with cross-linkers to form the
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
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.
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
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 300o
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.
It provides improved elegance, stability and
The drug is protected from degradation.
It is non-mutagenic.
Improve aqueous solubility of lipophilic drugs.
In this technology provide entrapment of active
contents and side effects are less.
It can be used to mask unpleasant flavors and to
convert liquid substances to solids.
Nanosponge particles are soluble in water and
encapsulation can be done within the nanosponge.
To increased the speed to reduced the size of
Nanosponges can significantly reduce the irritation of
drugs without reducing their efficacy.
To improving patient compliance by prolonging dosing
Easy scale-up for commercial production.
It depends upon only loading capacities.
It includes only small molecules, not large molecules.
Dose dumping may take place.
May retard the release
Polymers : Hyper cross linked polystyrenes, ethyl cellulose, 2-
hydroxy proply β – cyclodextrins, poly valerol actone,
Eudragit RS 100, acrylic polymers
Cross linkers : Carbonyl diimidazoles, Carboxylic acid di
anhydrides, Di aryl carbonates, Dichloromethane, Di
isocyanates, Di phenyl Carbonate, Epichloridine, Gluteraldehyde,
Pyro mellitic anhydride, 2,2-bis (acrylamido)Acetic acid.
Co Polymers :Poly(valerolactoneallylvalerol actone),
Poly(valerol actone-allylvalerol actone oxepanedione),Ethyl
Cellulose, Poly vinyl alcohol.
active ingredient is added to vehicles in the entrapped form
since nanosponges have an open structure the active substance
is free to move in or out from the particles into the vehicle until
the equilibrium is reached.
Once the product is applied on the skin, the active substance
that is already in vehicle which will become unsaturated,
therefore disturbing the equilibrium.
This will start flow of active from nanosponges particle into
vehicle from it, to skin until vehicle is either dried or absorbed.
Even after that nanosponges particle retained on the surface
of stratum corneum will continue to gradually release active
substance to skin providing as a targeted site and prolonged
release over time.
1.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.
2.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.
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.
4.Method of preparation :
The method of loading the drug into the nanosponge can
affect Drug/Nanosponge complexation.
5.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.
1. Solvent method
2. Hyper Cross- Linked β- Cyclodextrins
3. Emulsion Solvent Diffusion Method
4. Ultrasound-Assisted synthesis
Hyper Cross- Linked β- Cyclodextrins
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.
Emulsion Solvent Diffusion Method
• 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.
Loading Of Drug Into NanospongesLoading Of Drug Into Nanosponges
(undissolved) drug by
Then obtain the solid
crystals of nanosponges
1. Particle Size Determination
2. Loading Efficiency
3. Entrapment efficiency
4. Saturation state interaction
6. Zeta potential
7. SEM and TEM
8. Fourier transform-infrared spectroscopy (FTIR)
9. Powder X-ray diffraction (P-XRD)
10. Thermo gravimetric analysis (TGA)
12. Solubility studies
13. Swelling and water uptake
14. Drug release kinetics
1.Particle Size Determination :
Particle size can be determined by laser light diffractometry or Zeta seizer.
2.Loading Efficiency :
The loading efficiency (%) of Nanosponge can be determined by,
Actual drug content
Loading Efficiency = ---------------------------------- X 100
Theoretical drug content
To calculate the entrapment efficiency, weigh accurately
quantity of nanosponges into a suitable solvent in a volumetric
flask was shaken for 1 min. using vortex mixer. The volume was
made up to 10 ml with solvent. Then the solution was filtered
and diluted with the concentration of drugs was determined by
The yield of nano particles can be determined by calculating
initial weight of nanosponges as,
4.Saturation state interaction:
UV spectroscopy is used to carry out the saturated solution interaction
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.
Percent porosity is given by equation
Bulk volume – True volume
% Porosity (E) = ------------------------------------------ x 100
6.Zeta potential :
Zeta potential of any system under investigation is a measure of the
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
8.Fourier transform-infrared spectroscopy (FTIR) :
It serves as a major tool to determine the presence of functional
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
10.Thermo gravimetric analysis (TGA):
These studies are carried out to understand the melting point,
thermo stability and crystalline behaviour of the particle.
To determine the viscoelastic properties of nanosponges.
Viscoelastic properties of sponges is modified to produce bead
lets which are softer and firmer when needed for final
formulation. When cross linking got increased and tends to
slowdown rate of release. Resiliency are studied according to
requirement by releasing function of cross-linking with time.
14.Drug release kinetics:14.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 hr.
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
1. Targeted drug delivery:
These nanosponges circulate in the body until they encounter
the surface of a tumor cell, these nanosponges adhere to the
surface and begin releasing the drug in a controllable and
predictable manner. The controlled-release rate of
nanoparticle drug delivery system used a targeting peptide that
recognize daradiation –induced cell surface receptor. This
targeting agent combined a recombinant peptide with a
paclitaxel encapsulating nanoparticle that specifically targeted
to irradiated tumours, there by increasing apoptosis and
tumour-growth delay. Nanosponges loaded with an anticancer
drug, the delivery system is 3 to 5 times more effective than
direct injection at reducing tumour growth.
2. Oral drug delivery:
In oral administration, the complexes may be dispersed in a matrix
of excipients, diluents, lubricants and anti caking agents suitable for
the preparation of capsules or tablets. Acetyl salicylic acid(ASA), a
non steroidal anti-inflammatory drug mainly belonging toBCS class
III drugs, was formulated the preparation of nanosponges for oral
3.Topical drug delivery
Nanosponges formulation can be used in gels or creams for topical
application. Resveratrol-loaded nanosponges were seen to
enhancement of drug permeation in in-vitro studies on porcine
skin. The ability of nanosponges to increase the uptake of the guest
molecule by the skin can be attributed to the capacity to increase
solubility at the surface of the skin.
4. Solubility enhancement:
One of the greatest limits to the development of various
pharmaceuticals is the low water solubility of many drugs. About
40% of new marketed drugs are poorly soluble in water, which
hinders their clinical application. Nanosponges formulation can
improve the solubility of drug molecules with very poor solubility in
water. The drugs can be molecularly dispersed within the
nanosponge structure and then released as molecules, avoiding the
dissolution step. Consequently, the apparent solubility of the drug
can be increased. Drugs like Itraconazole, Tamoxifen, Paclitaxel and
ketoconazole are difficult to formulate due to their poor water
solubility can be easily formulated as nanosponges by enhancing
their solubility and attaining therapeutic efficacy.
5. In cancer treatment
In corporating the anticancer drug in the nanosponge allows the
use of hydrophobic drugs that do not dissolve readily in water. And
currently, these drugs must be mixed with adjuvant reagents,
which potentially can be reduce the efficacy of the drug or cause
side effect. The drug used for the animal studies was paclitaxel, the
active ingredient in the anticancer therapy Taxol. The researchers
recorded the response of two different tumour types-slow-growing
human breast cancer and fast-acting mouse glioma-to single
injections. In both cases, they found that the delivery through nano
sponges increased the death of cancer cells and delayed tumour
growth compared with other chemotherapy approaches.
6. In carrier for biocatalysts and release of enzymes,
proteins, vaccines and antibodies:
It includes the process applied in industry which correlate with
operational condition. There action which are not specific give rise
to low yields, require high temperature sand pressures which
consume large amount of energy and cooling water in down-
stream process. This is the drawbacks can be removed by using
enzymes as biocatalysts as this operate under high reaction speed,
7. Nanosponges as chemical sensors
The nanosponges which are the type of “metaloxides” act as a
chemical sensors, which is used in highly sensitive detection of
hydrogen using nanosponge titania because the chemical sensors.
Nanosponge structure initially have no point of contact so there is
less hindrance to electron transport and it results in higher 3D
interconnect nanosponges titania which is sensitive toH2 gas
Trade name Market
Dexamethasone Dermal Glymesason Japan
Iodine Topical Mena-gargle Japan
Alprostadil I.V Prostavastin Europe,
Piroxicam Oral Brexin Europe
Temoxifen Oral - -
Nanosponges is a tissue targeting site and drug release rate in
controlled and predictable manner. They are also capable of
carrying both lipophilic and hydrophilic molecules, due to their
small particle size and spherical shape.
The Nanosponges can be incorporated into the form of gel,
lotion, cream, ointment, liquid, powder and tablet form for oral
This technology offers loading of ingredients and it reduces the
side effects, increases elegance, improved stability and
increases the formulation flexibility.
In Nanosponges mainly consist of enhancement the rate of
solubilization of poorly water soluble drugs.
Nanosponge is an emerging technology for topical drug delivery.