NANOSPONGES: A NEW ERA OF VERSATILE DRUG DELIVERY SYSTEM
Neha Rahi, Kapil Kumar
Department of Pharmaceutics, Global Institute of Pharmaceutical Education and Research, Jaspur Road, Kashipur, US Nagar, Uttarakhand, India.
*Corresponding Author’s Email: neharahi1245@gmail.com
DOI: http://doi.org/10.22270/ujpr.v2i3.RW4
Nanotechnology is a multi disciplinary science which is getting considerable attention in development of new chemical entities, diagnosis and treatment of several ailments. Nanomedicine technology has developed many drug delivering systems like nanoparticles, nanoemulsions, nanosuspensions, nanosponges etc., which are associated with many advantages including improved bioavailability. Nanosponges are tiny sponges having size of about a virus and can be filled with variety of drugs. This sponge can circulate around the body until interact with specific target site and stick on surface and start releasing drug in a controlled manner.
Nanosponge play vital role in targeting drug delivery in a controlled manner. Both lipophilic and hydrophilic drugs are incorporated in nanosponges. The outer surface is typically porous, allowing controlled release of drug. Important characteristic of these sponges is their solubility in aqueous form and suitable for the drugs with poor solubility. This review is focusing on the preparation methods, applications of nanosponges in the field of drug delivery.
Keywords: Nanosponges, nano delivery, targeted site.
INTRODUCTION
The drug delivery technology has certainly a new interest for drugs by providing them new life through their therapeutic targets. Targeting drug delivery is the major problem which is being faced by the researchers. Target oriented drug improvements in therapeutic efficacy, reduction in side effects and optimized dosing regimen, shall be the leading trends in the area of therapeutics1. Targeted drug delivery implies for selective and effective localization of pharmacologically active moiety at preidentified (preselected) target in therapeutic concentration, while restricting its access to non-target normal cellular linings and thus minimizing toxic effects and maximizing therapeutic index of the drug2. They provide excellent topical delivery of drugs3. These embraces nanotechnology which is applied to pharmacy as nano materials, diagnosing and focusing right place in the body and controlling release of the drug4. Nanosponges is about the size of virus which has been backed by naturally degradable polyster. These tiny sponges can circulate around the body they encounter the specific target site and stick on the surface and began to release the drug in a controlled and predictable manner. Owing to their small size and porous nature they can bind poorly- soluble drugs within the matrix and improve their bioavailability. These are solid in nature and it can be formulated as oral, parenteral, topical or inhalational dosage forms. For oral administration, nanosponges may be dispersed in a matrix of excipients, diluents, lubricants and anti-caking agents which is suitable for the preparation of tablets or capsules.
Figure 1: Structure of Nanosponge
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 hydrogel5.
Advantages
Disadvantages:
1) Nanosponges include only small molecules9.
2) Depend only upon loading capacities.
Table 1: Chemicals used for the synthesis of nanosponges
|
Polymers
|
Hyper cross linked Polystyrenes, Cyclodextrines and its derivatives like Methyl β-Cyclodextrin, Alkyloxycarbonyl Cyclodextrins, 2-Hydroxy Propyl β-Cyclodextrins and Copolymers like Poly(valerolactone-allylvalerolactone) and Poly(valerolactone allylvalerolactoneoxepanedione), Ethyl Cellulose and PVA |
|
Crosslinkers |
Diphenyl Carbonate, Diarylcarbonates, Diisocyanates, Pyromellitic anhydride, Carbonyldiimidazoles, Epichloridrine, Glutarldehyde, Carboxylic acid dianhydrides, 2,2- bis(acrylamido) Acetic acid and Dichloromethane |
|
Apolar solvents |
Ethanol, Dimethylacetamide, Dimethyl formamide |
SYNTHESIS OF NANOSPONGES
It is one of the important criteria for the formation of product obtained activity in β-cyclodextrin, titanium oxide.
The solvent required is mixed with the polymer mainly in a polar aprotic solvent, for example dimethyl formide, dimethyl sulfoxide then add this mixture to cross linker in a exceed quantity, the ratio for cross linker/ molar ratio is preferred as 4 to 16. The reaction is proceeded with a solvent reflux temperature and time ranging from 1 to 48 hr. The cross linkers which may preffered are dimethyl carbonate and carbonyl di-imidazole10. The reaction is completed and solution is allow to cool at room temperature then product is added to excess of bi-distilled water and product is recovered by filtration under vaccum and simultaneously purify by prolonged soxhlet extraction with ethanol. Finally product is dried under vaccum and grinded in a mechanical mill to obtain homogeneous powder11.
Nanosponges are obtained by reacting polymer with cross linkers without adding or without using solvent and sonification is maintained. The polymer is mix with a cross linkers in a balanced ratio in a flask. The flask is placed in a molar ratio in an ultrasound bath field with water and temperature maintained at 90 ºC, the mixture is sonicated for 5 hrs12. 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. The product is dried under vaccum at 25ºC until its further use is utilized13.
Nanosponges obtained should be pretreated to maintain mean particle size blow 500nm. Nanosponges are suspended in water and were sonicated to avoid presence of aggregates and particles and got centrifuged to obtain colloidal fraction, then supernatant is separated and dried sample by freezing by drying14. Further proceeding start with preparing aqueous suspension of nanosponges and excess amount of drug is dispensed for maintaining suspension under constant stirring for specific time period for complexation is over the undissolved drug (uncomplexed condition) is separated from complexed drug with the process of centrifugation. This process helps in evolving solid crystals of nanosponges by solvent evaporation or freeze drying. Para-crystalline nanosponges revealed different loading capacities when compared to crystalline nanosponges poorly crystalline nanosponges had act drug loading as a mechanical mixture rather than inclusion complex15.
FACTORS INFLUENCE NANOSPONGE FORMATION
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 size16.
Drug molecules to be complexed with nanosponges should have certain characteristics mentioned below17-
Temperature changes can affect drug/nanosponge complexation. In general, increasing in the temperature decreases the magnitude of the apparent stability constant of the drug/ nanosponge complex may be due to a result
of possible reduction of drug/ nanosponge interaction forces, such as Van-der Waal forces and hydrophobic forces with rise of temperature18.
PHYSICOCHEMICAL CHARACTERIZATION OF NANOSPONGE
Free-flowing powders with fine aesthetic attributes will possible to obtain by controlling the size of particles during polymerization. Particle size analysis of loaded and unloaded nanosponges will performed by laser light diffractometry or Malvern Zeta sizer. Particles larger than 30 m can impart gritty feeling and hence particles of sizes between 10 and 25 m are preferred to use in final topical formulation19.
The prepared nanosponge loading efficiency is determined by subtracting the un-entrapped drug from the total amount of drug. The drug entrapment efficiency will be determined by separating un-entrapped drug estimated by any suitable method of analysis20. The method used for separation of un-entrapped drug by gel filtration, dialysis and ultra centrifugation21.
Porosity study is performed to check the extent of nanochannels and nanocavities formed. Porosity of nanosponges is assessed with a helium pycnometer, since helium gas is able to penetrate inter- and intra-particular channels of materials. The true volume of material isdetermined by the helium displacement method. Owing to their porous nature, nanosponges exhibit higher porosity compared to the parent polymer used to fabricate the system22.
For swellable polymers like polyamidoamine nanosponges, water uptake can be determined by soaking the prepared nanosponges in aqueous solvent23. Swelling and water uptake can be calculated using equations:
Resiliency of sponges can be modified to produce beadlets that is softer or firmer according to the needs of the final formulation. Increased crosslinking tends to slow down the rate of release. Hence resiliency of sponges will be studied and optimized as per the requirement by considering the release as a function of cross-linking with time24.
Zeta potential is a measure of surface charge. The surface charge of nanosponges can be determined by using Zeta sizer25.
Dissolution profile of Nanosponge can be studied by use of the dissolution apparatus usp XXIII with a modified basket consisted of 5m stainless steel mesh. Speed of the rotation is 150 rpm. The dissolution medium is selected while considering solubility of actives to ensure sink conditions. Samples from the dissolution medium can be analyzed by a suitable analytical method studied by use of the dissolution apparatus USP xxiii with a modified basket consisted of 5m stainless steel mesh. Speed of the
rotation is 150 rpm. The dissolution medium is selected while considering solubility of actives to ensure sink conditions. Samples from the dissolution medium can be analyzed by a suitable analytical method26.
The diffusion studies of the prepared nanosponge can be carrying out in Franz diffusion cell for studying the dissolution release of nanosponge through a cellophane membrane. Nanosponge sample (0.5g) can taken in cellophane membrane and the diffusion studies were carried out at 37±1°C using 250 ml of phosphate buffer (pH 7.4) as the dissolution medium. 5ml of each sample can withdrawn periodically at 1, 2, 3, 4, 5, 6, 7 and 8 hrs and each sample will replaced with equal volume of fresh dissolution medium27.
APPLICATIONS OF NANOSPONGES
Because of their nonporous structure, nanosponges can advantageously carry water insoluble drugs (Biopharmaceutical Classification System class-II drugs). These complexes can be used to increase the dissolution rate, solubility and stability of drugs, to mask unpleasant flavors and to convert liquid substances to solids28.
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 intially 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 gas29.
In oral application it forms the nanosponge system consist of pores which increase the rate of solubilization of poorly water soluble drugs which get entrapped the drug in pores. The surface area is increased due to nanosize form and increase rate of solubilization30.
β-cyclodextrin based nanosponges of itraconazole have enhance solubility of poorly soluble drug. The solubility increased by 50 folds compared to ternary dispersion system e.g. - copolyvidonum30.
It includes the process applied in industry which correlates 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 condition31.
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, Saquinavir32.
Targeting drug to specific site avoiding the obstacle created by immune system. Different cancer cells had been treated by nanosponges like breast cancer or fast acting glioma type with help of single dose of injections33.
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 system34.
CONCLUSION
Nanosponges are tiny mesh-like structures that may revolutionise the treatment of many diseases and this technology is five times more effective at delivering drugs for cancer than conventional methods. Because of their small size and spherical shape nanosponges can be developed as different dosage forms like parenteral, aerosol, topical, tablets and capsules. Nanosponge are nano sized colloidal carrier so they easily penetrate through skin. 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. The nanosponges have the ability to incorporate many drugs and release them in a controlled and predictable manner at the target site. Topical nanosponge can be more patient compliant and provide sufficient patient benefits by reducing repeated doses and side effects. Nanosponge can be effectively incorporated into topical drug delivery system for retention of dosage form on skin. Hence present study concludes that nanosponges may play an important role for the treatment of different diseases.
REFERENCES