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they can be effectively incorporated into topical be heated to 90 C. The mixture was sonicated for5
hydrogel[19,20] h. Then the mixture was allowed to cool and the
productwas broken roughly. After that, the product
was washed with water toremove the non reacted
polymer and subsequently purifiedby prolonged
Soxhlet extraction with ethanol. Theproduct was
dried under vacuum and stored at 25 C [17,22].
Loading of drug into nanosponges:
Nanosponges for drug delivery should have a mean
particle size below 500 nm. The nanosponges were
suspended in water and sonicated to prevent the
presence of aggregates and then centrifuged the
suspension to get the colloidal fraction. The
supernatant was separated and dried the sample by
freeze drying[22]. The aqueous suspension of
nanosponges was dispersed the excess amount of the
drug and the suspension was maintained under
constant stirring for specific period of time required
for complexation. The uncomplexed (undissolved)
drug was separated from complexed drug by
Figure-A: Molecular structure of cyclodextrin centrifugation after complexation. Then solvent
carbonates nanosponges. [7-9]. evaporation or freeze drying is carried out to get the
FORMULATION TECHNIQUES OF solid crystals of nanosponges[18,22]. Crystal
NANOSPONGE structure of nanospongeis very important in
Solvent method: complexation with drug. A study showed that
In this method, suitable solvent was mixed with the paracrystallinenanosponges revealed different
polymer, in particular in a polar aprotic solvent such loading capacities when compared to crystalline
as dimethylformamide, dimethylsulfoxide. This nanosponges. The drug loading is better in
mixture was added to excess amount of the crystalline nanosponges than paracrystalline one.
crosslinker, especially in crosslinker/polymer molar
ratio of 4 to 16. The reaction was carried out at CHARACTERIZATION OF NANOSPONGES
temperature ranging from 10 C to the reflux Particle size:
temperature of the solvent, for time ranging from 1 A scanning electron microscope (Zeiss,
to 48 h. Carbonyl compounds are the preferable Germany)was used to scan the surface morphology
cross linker (dimethylcarbonate and carbonyl of nanosponges. The samples weremounted on
diimidazole)[18].After the reaction is completed, the aluminum stub with adhesive tape and coated
solution was allowedto cool at room temperature. withplatinum/palladium alloy under vacuum. ). The
After that, the product was added tolarge excess of difference in crystallization state of the raw
bidistilled water and the product was recovered by materials and the product observed under electron
filtration under vacuum and subsequently purified microscope indicates the formation of the inclusion
byprolonged Soxhlet extraction with ethanol. The complexes[23,24].
product wasdried under vacuum and grinded in a Particle size analysis
mechanical mill toget homogeneous powder[22]. Particle size of the nanosponge formula-tions was
Ultrasound-assisted synthesis: measured by a laser light scattering particle size
According to this method, nanosponges were gained analyzer [25]. Samples were added in water and
by reactingpolymers with crosslinkers in the absence such suspensions stirred when the particle size
of solvent andunder sonication. Spherical and analysis. Triplicate measurement was done.
uniform size of the nanosponges will be obtained by Zeta potential analysis
this method[17]. The polymer wasmixed and the Zetasizer was used to measured the zeta potential of
crosslinker in aexact molar ratio in a flask. The flask nanosponges(Malvern instruments, UK) at 25C.
which put in an ultrasound bath filled withwater will Before the measurement, nanosponge formulations
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Lim Kuan Ting,: Recent Trends on Nanosponge
werediluted with deionized water. Each the mechanical mixture of the drug and polymer
measurement was carried out in triplicate [26] molecules when the drug compound is in solid
Moisture uptake studies state[29].
Three nanosponge formulations were open to three A diffraction pattern of a physical mixture is
differenthumidity conditions at 23C. Various frequently the total of those of each component,
saturated salt solutionslike calcium carbonate in while the diffraction pattern of complexes is
31% RH desiccator, potassium nitrate in45% RH apparently vary from each constituent and leads to a
desiccator, and ammonium chloride in 79.3% RH new solid phase with various diffractograms.
desiccator were used to construct the controlled Diffraction peaks for a mixture of compounds are
humidity in desiccators . Formulations were responsible for the chemical decomposition and
subjected to these various humidity for 30 days [27]. complex formation[29]. The diffraction patterns and
Encapsulation efficiency the crystalline nature of the drug are altered by the
The calcium content of nanosponge formulations complex formation of drug with nanosponges. The
(F1, F2 andF3) was assayed by Atomic Absorption complex formation leads to the improving of the
Spectrophotometer [25]. Formulations of existing peaks, appearance of a few new peaks and
nanosponges equivalent to 250 mgof calcium changing of certain peaks[29].
carbonate were dissolved in few millilitre of 6 M Thin layer chromatography:
HCIthen diluted with deionized water. The The Rf values of a drug molecule diminish to
concentrations of calciumin these formulations were considerable extent and this available to know the
calculated. complex formation between the drug and
In vitro release study nanosponge[29].
In vitro, dissolution test apparatus (Electrolab, USA) APPLICATIONS OF CYCLODEXTRIN
USP apparatus II was used to perform the releasing NANOSPONGES IN PHARMACEUTICALS
of calcium from nanosponges formulations at 50 Nanosponges prepared from cyclodextrins are used
rpm at 37C. A 100 mg of formulation was placed as drug carriers in pharmaceutical formulations.
500 ml of simulated gastric fluid (pH 1.2) for first2 Molecular encapsulations of the drug and other
h and then it was transferred in 500 ml phosphate modifications with suitable cyclodextrin based
buffer (pH 7.0) and aliquot samples were nanosponges can solve the problems such
withdrawn.at specific time interval. Atomic aspermeability, insolubility, sensitivity, etc., and
absorptionspectrophotometer was used to determine facilitate safe and efficient delivery of drugs [30].
the calcium content in the sample. Nanosponges can carry water insoluble drugs and
Accelerated stability study BCS (Biopharmaceutical Classification System)
The accelerated stability study was carried out based class-II and IV drugs and can be also used to
according to ICHguidelines [28]. Sealed vial of enhance the dissolution rate, solubility and stability
freshly prepared formulation (F3) were placed in of such drugs. Nanoporous structures enable
stability chamber maintained at 25C,60% RH. The entrapment of flavors by adsorption.Therefore,it
formulations subjected to stability tests were helps to mask the unpleasant flavors and also
analyzedfor 3 months period for its physical changes liquid substances to solids. Nanosponges
appearance, size and nature ofdrug with a frequency can adsorb odorous material and hence facilitate its
of 1 month sampling. removal from organic materials, water and other
X-ray diffractiometry and single crystal X-ray products. Nanosponges are solid in nature and can
structure be easily formulated as oral, parenteral, topical or
Inclusion complexation in the solid state can be inhalation dosage forms.Some specific applications
detected by Analysis Powder X-Ray diffractiometry. of CD based nanosponges include the following:
Since the drug molecule is liquid have no diffraction Enhancement of drug stability:
pattern, then the diffraction pattern of a newly b-CD units are conjugated with a polymer, where a
formed substance clearly differs from that of number of b-CD units are bound to the same
uncomplexednanosponge. The complex formation is polymer chain. Several b-CD units improve the
indicated by the difference of diffraction pattern., A stability of the drug complex [31]. Moreover, the
comparison has to be made between the polymer may work together with the b-CD moieties
diffractogram of the assumed complex and that of in stabilizing the complexes. Such studies have been
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Lim Kuan Ting,: Recent Trends on Nanosponge
carried out for proteins and peptides due to their Complexes showed greater effect than that of
insufficient stability, costly production, thedrug alone [36].
immunogenic, allergic potential and also poor Solubility enhancement:
bioavailability and sensitivity towards proteases [32]. The presence of cross-linking and cyclodextrin
Bovine serum albumin (BSA) proteins in solution cavities in the structure enhances the interaction
are unstable, they are stored in lyophilized state. with active molecules. These characteristics allows
Nonetheless, proteins can get be denatured on different substances to be solubilized in the formed
lyophilization and get conformation different from cavities. Inclusion complexation or solid dispersions
the native structure. A major demerit is protein with CDs can enhance drug solubility or rate of
formulation and development is the need to maintain dissolution of poorly water-soluble drugs because of
its native structure during processing and long-term the reduction in drug crystallinity. Most of
storage [33]. hydrophobic functionality in the interior cavity of
Nanosponges as carriers for enzymes, the CD hide by resulting complex while polar
proteins,vaccines and antibodies: hydroxyl groups on the external surface remain
Proteins, peptides, enzymes and derivatives are exposed to the environment; as a result water
helpful in the biomedical and therapeutic fields. soluble complex is formed [37]. Methylated CDs
Proteolytic enzymes are used to treat cancer or type with relatively low molar substitution are the most
I mucopolysaccharidosis, while DNA and powerful solubilizers. CD nanosponges can further
oligonucleotides are used in gene therapy. enhance drug dissolution even when there is no
Administration of these molecules presents different complexation and act as release enhancers [35].
limitations [34]. There are some concerns with CDs also enhance the permeability of hydrophobic
enzyme, vaccine and antibody stability. Proteins and drugs by improving drug solubilityand dissolution.
other macromolecules can be delivered across a Therefore, it makes them free at the surface of the
biological barrier, targeting them towards the site by biological barrier, wherefrom they partition into the
adsorbing or encapsulating them in membrane without disturbing the lipid layers of the
cyclodextrinnanosponges. barrier. Comparison of improved aqueous solubility
Modifying drug release: of lipophilic drugs was made with the hydrophilic
Often administration is the major demerit of most of drug doxorubicin after the drugs were loaded into
the commercially available delivery systems. nanosponges. This action could be ascribed to the
Nevertheless, a drug loaded in the nanosponge larger number of lipophilic sites free for the
structure can be hold and released slowly over complexation of lipophilic drugs in comparison with
time.The rate of drug release of hydrophilic CD NS the hydrophilic sites on the cyclodextrin cage [36].
can be changed, which can be used for enhancement CONCLUSION
of drug absorption across biological barriers, act as a The nanospongesare able to release the drug in a
potent drug carrier in immediate release controlled manner to the targeted site. They have the
formulations. It may act as sustained release carriers ability of carrying both non-polar and polar
for water-soluble drugs, including peptide and molecules. Due to their small particle size and
protein drugs [35]. spherical shape these can be developed as different
Anticancer drug therapy: dosage forms like oral, parenteral and topical
They may provide protection for the drug during its preparations. Nanosponges technology offers variety
passage through the stomach. This drug is released entrapment of ingredients and as a result lowered
slowly at pH 1.1, whereas release is faster if pH is side effects, enhanced stability, improved elegance
raised to 7.4. and enhanced formulation flexibility. Hence,
Effective delivery carriers: nanosponges technology bring site specific drug
For instances, Cyclodextrinnanosponges have been delivery and prolongs dosage time intervals and thus
used as antitumor drugs such as paclitaxel, patient compliance. Nanosponge formulation could
camptothecin and tamoxifen which present be the best solution for solving various nano related
bioavailability problems due to their solubility in issues in the pharmaceutical industry.
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