Nanosponges: Novel Targeted Drug Delivery System

A Presentation on Nanosponges

1. PRESENTED BY: PRATHMESH SHIRSEKAR GUIDED BY: MR. NITIN KOLHE (ASSISTANT PROFESSOR) LSHGCT’s GAHLOT INSTITUTE OF PHARMACY NANOSPONGES: Novel Targeted Drug D elivery S ystem 1

2. CONTENT Introduction Advantages Factors influencing formation of nanosponges Method of preparation Evaluation Application Conclusion Reference 2

3. DEFINATION 3 Nanosponge are tiny sponges with a size about a virus (205nm – 1µm) which consist of cavities that can be filled with wide variety of drugs. The sponge act as a three-dimensional network or scaffold, which consist of the backbone known as long-length polyester. It is mixed in solution with cross-linkers to form polymer.

4. INTRODUCTION 4 Nanosponge is a novel and emerging technology which play a vital role in targeting drug delivery in a controlled manner. Nanosponge are a new class of materials and made of microscopic particles with a few nanometers wide cavities in which a large variety of substances can be encapsulated. These particles are capable of carrying both lipophilic and hydrophilic substances and of improving the solubility of poorly water soluble molecule.

5. 5 Nanoscale materials are small enough to be effective in attaching or passing through a cell membrane. The polyester is biodegradable, so it breaks down gradually in the body and releases its drug payload in a predictable fashion. These tiny sponges can circulate in the body until they encounter a 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 upto 300°C.

6. ADVANTAGES 6 Nanosponge formulations are stable over range of pH 1-11. Compatible with most vehicles and ingredients. These are self sterilizing as their average pore size is 0.25µm where bacteria cannot penetrate. Improve patient compliance by prolonged dosing interval. Improves aqueous solubility of the lipophilic drug. Prevents degradation of the drug. Predictable release and non-toxic. Easy scale-up for commercial production.

7. MATERIALS USED FOR NANOSPONGES 7 Polymers: Hyper cross linked polystyrenes, ethyl cellulose, 2-hydroxypropyl β-cyclodextrins, polyvalerolactone, Eudragit RS100, acrylic polymers. Cross-linkers: Carbonyldiimidazoles, Carboxylic acid dianhyrides,Diarylcarbonates,Dichloromethane,Diisocyanates,Diphenylcarbonate,Epichloridine,Gluteraldehyde,pyromellitic anhydride, 2,2-bis(acrylamido)acetic acid. Co-Polymer: Poly (valerolactone allylvalerolactone), Poly(valerolactone allylvalerolactone oxepanedione), Ethyl Cellulose, Poly vinyl alcohol

8. FACTORS INFLUENCING NANOSPONGES 8 Polymer: Type of polymer used can influence the formation as well as performance of nanosponges. Characteristics of drug: Molecular weight between 100-400Da. Molecule consists of less than five condensed rings. Solubility less than 10mg/ml. Melting point below 250°C. Temperature Method of preparation Degree of substitution: The complexation ability of nanosponge can be altered by the substituent on the parent molecule.

9. HYPER CROSS-LINKED β CYCLODEXTRINS 9 The crosslinker is melted along with CD, all the ingredients are finely homogenized and placed in a 250ml flask heated at 100°C and the reaction is carried out for 5hrs with magnetic stirring. 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 the product. The reaction is carried out at temperature ranging from 10°C to the reflux temperature of the solvent for 1 to 48hrs.

10. 10 Preferred cross linkers for this reaction are the carbonyl compounds diphenyl carbonate, dimethyl carbonate or carbonyl diimidazole. The product is obtained by adding the cooled solution to a large excess of D.W. Recovery of the product is done by filtration under vacuum and the product is further purified by prolonged Soxhlet extraction.

11. EMULSION SOLVENT DIFFUSION METHOD 11 Nanosponges are prepared by using different proportion of ethyl cellulose and polyvinyl alcohol. 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. The reaction mixture was stirred at 1000rpm for 2hrs. The nanosponge formed were collected by filtration and dried in oven at 40°C for 24hrs and stored in vacuum.

12. ULTRASOUND-ASSISTED SYNTHESIS 12 Nanosponges are obtained by reacting polymer with cross linkers without using solvent and sonication is maintained. The size obtained by this method will be spherical and uniform. The polymer is mix with the a cross linker 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°C, the mixture is sonicated at 5hr.

13. 13 Then the mixture is kept 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 vacuum at 25°C until its further use is utilized.

14. MECHANISM OF NANOSPONGES 14 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 substances from nanosponge particle into vehicle from it, to skin until vehicle is either dried or absorbed.

15. 15 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.

16. LOADING OF DRUG INTO NANOSPONGES 16

17. EVALUATION OF NANOSPONGES 17 Particle size Loading efficiency Entrapment efficiency Saturation state interaction Porosity Fourier transform infrared spectroscopy Powder X-ray diffraction Thermo gravimetric analysis (TGA) Solubility studies

18. APPLICATIONS 18 Nanosponges as chemical sensor: Nanosponges which are type of metal oxide act as chemical sensor 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 nanosponge titania which sensitive to H 2 gas. Biomedical applications: Nanosponge can be used for contaminated water. Nanosponge have been used to remove organic impurities from the water.

19. 19 Oxygen delivery system: Characterized by using α , β and γ 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 help of nanosponge. They can also applied it to hypoxic tissues caused various types of disease. 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. E.g.. Copolyvidonum.

20. 20 Nanosponges as a carrier for biocatalyst and release of enzymes, proteins, vaccines and antibodies: It includes the process applied in the industry which corelate with operational condition. Reactions which are not specific give rise to low yields and require high temperature and pressure which consume large amount of energy and cooling water in down stream process. This drawbacks can be removed by using enzyme as biocatalyst, as this operates under high reaction speed, mild condition.

21. 21 Topical agents: Nanosponge delivery system is a unique technology for controlled release of topical agents of prolonged drug release and retention of drug form on skin. Antiviral application: Nanosponge used in nasal, pulmonary route of administration. It provides 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. Drug used as nanocarriers are Zidovudine, Saquinavir.

22. MARKETED PREPARATION 22 Other patented drug used in nanosponge preparation are Temoxifen, Paclitaxel, Camptothecin, Econazole nitrate. DRUG ADMINISTRATION ROUTE TRADE NAME MARKET DEXAMETHASONE DERMAL GLYMESASON JAPAN IODINE TOPICAL MENA-GARGLE JAPAN ALPROSTADIL I.V PROSTAVASTIN EUROPE, USA PIROXICAM ORAL BREXIN EUROPE

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24. CONCLUSION 24 From the above study we conclude that, the nanosponge include lipophilic and hydrophilic drugs and release the drug at target site in controlled manner. Nanosponge permit the insoluble drug and prevent the physiochemical degradation of active content and controlled release. Thus nanosponge is boon to the targeted drug delivery system.

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