Preparation and application of Niosomes

NIOSOMES , GENERAL CHARACTERISTICS OF NIOSOME , TYPES OF NIOSOMES , OTHERS TYPES OF NIOSOMES , NIOSOMES VS LIPOSOMES , COMPONENTS OF NIOSOMES , Non-ionic surfactant , Cholesterol , Charge inducing molecule , METHOD OF PREPARATION , preparation of small unilamellar vesicles , Sonication , Micro fluidization , preparation of large unilamellar vesicles , Reverse Phase Evaporation , Ether Injection , preparation of Multilamellar vesicles , Hand shaking method , Trans membrane pH gradient drug uptake process (remote loading) , Miscellaneous method :Multiple membrane extrusion method , The “Bubble” Method , Formation of Niosomes From Proniosomes , SEPARATION OF UNENTRAPPED DRUGS , Gel Filtration , Dialysis , Centrifugation , FACTORS AFFECTING THE PHYSICOCHEMICAL PROPERTIES OF NIOSOMES , Membrane Additives , Temperature of Hydration , PROPERTIES OF DRUGS , AMOUNT AND TYPE OF SURFACTANT
Structure of Surfactants , Resistance to Osmotic Stress , Characterization of niosomes ,Therapeutic applications of Niosomes , For Controlled Release of Drugs , To Improve the Stability and Physical Properties of the Drugs , For Targeting and Retention of Drug in Blood Circulation , Proniosomes , Aspasomes , Vesicles in Water and Oil System (v/w/o) ,Bola - niosomes , Discomes , Deformable niosomes or elastic niosomes , According to the nature of lamellarity ,Small Unilamellar vesicles (SUV) 25 – 500 nm in size.,Large Unilamellar vesicles (LUV) 0.1 – 1μm in size , Multilamellar vesicles (MLV) 1-5 μm in size , According to the size:Small Niosomes (100 nm – 200 nm) , Large Niosomes (800 nm – 900 nm),Big Niosomes (2 μm – 4 μm)

1. NIOSOMES 1 Presented by P.Pavazhaviji M.Pharm I Year (II Sem ) Dept. of Pharmaceutics MTPG & RIHS Puducherry

2. DEFINITION Niosomes are a novel drug delivery system , in which the medication is encapsulated in a vesicle , composed of a bilayer of non – ionic surface active agents and hence the name niosomes . Niosomes also called as nonionic surfactant vesicles or NSV s . Nios = non ionic surfactant Somes = vesicles 2

3. STRUCTURE 3

4. GENERAL CHARACTERISTICS OF NIOSOME Biodegradable Biocompatible N on-toxic Non-immunogenic N on-carcinogenic High resistance to hydrolytic degradation 4

5. According to the nature of lamellarity 1. Small Unilamellar vesicles (SUV) 25 – 500 nm in size. 2 . Large Unilamellar vesicles (LUV) 0.1 – 1 μ m in size 3. Multilamellar vesicles (MLV) 1-5 μ m in size . According to the size 1. Small Niosomes (100 nm – 200 nm) 2. Large Niosomes (800 nm – 900 nm) 3. Big Niosomes (2 μ m – 4 μ m) TYPES OF NIOSOMES 5

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7. OTHERS TYPES OF NIOSOMES Proniosomes Aspasomes Vesicles in Water and Oil System (v/w/o) Bola - niosomes Discomes Deformable niosomes or elastic niosomes 7

8. ADVANTAGES OF NIOSOMES Targeted drug delivery Reduction in dose Decrease in the side effects Both hydrophilic and lipophillic drugs can be encapsulated Enhance the skin permeability of drugs The surfactants used and also the prepared niosomes are biodegradable, biocompatible and non-immunogenic They are osmotically active and stable 8

9. DISADVANTAGES OF NIOSOME F usion, Aggregation, L eaching H ydrolysis Time consuming Requires specialized equipment Inefficient drug loading High production cost 9

10. NIOSOMES VS LIPOSOMES Niosome Liposomes Niosomes are prepared from uncharged single – chain surfactant Liposomes are prepared from double – chain phospholipids Size ranges from 10-100nm Size ranges from 10-3000nm Chemically stable Chemically unstable Less expensive More expensive They do not require special storage and handling They require special storages Less toxic Comparatively more toxic 10

11. COMPONENTS OF NIOSOMES Non-ionic surfactant Cholesterol Charge inducing molecule 11

12. NON-IONIC SURFACTANTS The non-ionic surfactants orient themselves in bilayer lattices where the polar or hydrophilic heads facing hydrophilic region while the non-polar tails facing each other to form a hydrophobic region. 12

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14. CHOLESTEROL Cholesterol is a steroid derivative, which is mainly used for the formulation of niosomes. Although it may not show any role in the formation of bilayer. It makes the membrane rigid , increase the entrapment efficiency . It prevents the vesicle aggregation by the inclusion of molecules that stabilize the system against the formation of aggregates by repulsive steric or electrostatic forces .As a result of this, the niosome becomes less leaky in nature. 14

15. CHARGE INDUCING MOLECULE Some charged molecules are added to niosomes to increase stability of niosomes by electrostatic repulsion which prevents aggregation and coalescence. The negatively charged molecules used are diacetyl phosphate (DCP) and phosphotidic acid. Similarly, stearylamine (STR) and stearyl pyridinium chloride are the well known positively charged molecules used in niosomal preparations. Only 2.5-5 % concentration of charged molecules is tolerable because high concentration can inhibit the niosome formation. 15

16. METHOD OF PREPARATION : preparation of small unilamellar vesicles Sonication Micro fluidization preparation of large unilamellar vesicles Reverse Phase Evaporation Ether Injection preparation of M ultilamellar vesicles Hand shaking method Trans membrane pH gradient drug uptake process (remote loading ) Miscellaneous method : Multiple membrane extrusion method The “Bubble” Method Formation of Niosomes From Proniosomes 16

17. 1) Preparation of small unilamellar vesicles a) Sonication Niosomes sonicated for 3mins at 60°c using titanium probe Drug in buffer + surfactant /cholesterol in 10ml glass vial 17

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19. b) Micro fluidization Two ultra high speed jets inside interaction chamber Impingement of thin layer of liquid in micro channels Niosomes High speed impingment & the energy involved 19

20. 2) preparation of large unilamellar vesicles a) Reverse Phase Evaporation Surfactant + cholesterol (1:1) in organic solvent Drug in aqueous phase Sonicated at 4-5°c Add phosphate buffer saline & sonicate Viscous niosomes suspension diluted with PBS Organic phase is removed at 40°c Under low pressure Heated on a water bath at 60°c for 10 mins Niosomes 20

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22. b) Ether Injection Surfactant is dissolved in diethly ether Then injecting in warm water maintained at 60°c through 14 gauge needle at 0.25 ml/min Ether is vaporized Niosomes 22

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24. 3) preparation of multilamellar vesicles a) Hand shaking method Surfactant + cholesterol + volatile organic solvent Remove organic solvent at room temperature by rotary evaporator Thin layer formed on the wall of flas k Multilamellar niosomes Film can be rehydrated with drug & aqueous phase 24

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26. b) Trans membrane pH gradient drug uptake process (remote loading) Surfactant + cholesterol in chloroform Hydrated with citric acid by vortex mixing freezing & thawing then sonication Addition of aqueous drug solution & vortexed pH raised to 7.0-7.2 by 1M disodium phosphate Multilamellar niosomes Thin film is deposited on the wall of RBF 26

27. 4) MISCELLANEOUS METHOD : a) Multiple membrane extrusion method Surfactant + cholesterol + diacetyl phosphate dissolved in chloroform Niosomes Pass the mixture through a series of 8 polycarbonate membrane Aq. drug solution is added to above mixture Solvent evaporation to form thin film 27

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29. b) The “Bubble” Method 29

30. c) FORMATION OF NIOSOMES FROM PRONIOSOMES Another method of producing niosomes is to coat a water-soluble carrier such as sorbitol with surfactant The result of the coating process is a dry formulation. In which each water-soluble particle is covered with a thin film of dry surfactant. This preparation is termed “ Proniosomes” The N iosomes are formed by the addition of aqueous phase at T > Tm and brief agitation T = Temperature. Tm = mean phase transition temperature 30

31. SEPARATION OF UNENTRAPPED DRUGS The removal of unentrapped solute from the vesicles can be accomplished by various techniques, which include : Gel Filtration The unentrapped drug is removed by gel filtration of niosomal dispersion through a Sephadex-G-50 column and elution with phosphate buffered saline or normal saline . Dialysis : The aqueous niosomal dispersion is dialyzed in a dialysis tubing against phosphate buffer or normal saline or glucose solution Centrifugation : The niosomal suspension is centrifuged and the supernatant is separated. The pellet is washed and then resuspended to obtain a niosomal suspension free from unentrapped drug . 31

32. FACTORS AFFECTING THE PHYSICOCHEMICAL PROPERTIES OF NIOSOMES Membrane Additives: Stability of niosomes can be increased by the number of additives into niosomal formulation along with surfactant and drugs. e.g . Addition of cholesterol in niosomal system increases the rigidity and decreases the drugs permeability through the membrane Temperature of Hydration: Shape and size of niosome is also influenced by the hydration temperature. Assembly of the niosomes vesicles is affected by the temperature change of niosomal system. Temperature change can also induce the vesicle shape transformation 32

33. PROPERTIES OF DRUGS The drug entrapment in niosomes is affected by molecular weight, chemical structure, hydrophilicity, lipophilicity of the drug. Vesicle size may increase due to entrapment of drug. Nature of the drug Leakage from the vesicle Stability Hydrophobic drug Decreased Increased Hydrophilic drug Increased Decreased Macromolecule Decreased Increased 33

34. AMOUNT AND TYPE OF SURFACTANT As the HLB value of surfactants like span 85 (HLB 1.8) to span 20 (HLB 8.6) increased, the mean size of niosomes also increases proportionally. Entrapment efficiency is also affected by phase transition temperature i.e. span 60 having higher TC, provide better entrapment efficiency. Entrapment efficiency of the niosomes is affected by the HLB value for e.g. niosomes have high entrapment efficiency at HLB value 8.6 but HLB value 14 to 17 is not suitable for niosomes formulation 34

35. Structure of Surfactants The geometry of vesicles to be formed from surfactant is affected by its structure, which is related to critical packing parameter (CPP ) where V= hydrophobic group volume Ic = the critical hydrophobic group length a0 = the area of hydrophilic head group spherical micelles formed if CPP<0.5, inverted micelles is formed if CPP>1. 37 35

36. Resistance to Osmotic Stress Diameter of niosomal vesicles was found to be decreased when niosomal suspension is kept in contact with hypertonic salt solution. There is slow release with slight swelling of vesicles, which is due to inhibition eluting fluids from vesicles, followed by faster release, which may be due to decrease in mechanical strength under osmotic stress 36

37. Characterization of niosomes Physical characterization Chemical characterization Biological characterization 37

38. Physical characterization 38

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40. Chemical characterization 40

41. Biological characterization 41

42. Therapeutic applications of Niosomes 1 ) For Controlled Release of Drugs 2 ) To Improve the Stability and Physical Properties of the Drugs 3) For Targeting and Retention of Drug in Blood Circulation 42

43. 1)To Prolong the Release Rate of Drugs 1.1 For Controlled Release The release rate of drugs like withaferin and gliclazide from the niosomes was found slower as compared to other dosage forms 1.2 In Ophthalmic Drug Delivery Experimental results of the water soluble antibiotic gentamicin sulphate showed a substantial change in the release rate. Beside this, the percent entrapment efficiency of gentamicin sulphate was altered when administered as niosomes . Also, as compared to normal drug solution, niosomes of drug show slow release Niosomal formulation containing timolol maleate (0.25%) prepared by chitosan coating exhibited more effect on intra ocular tension with fewer side effects as compared to the marketed formulation. 43

44. 2) To Improve the Stability and Physical Properties of the Drugs 2.1 To Increase Oral Bioavailability : the formulation of niosomes, the oral bioavailability of the acyclovir as well as griseofulvin was increased as compared to the drug alone. 2.2 For Improvement of Stability of Peptide Drugs : Niosomes prepared by the span 60 has high resistance against proteolytic enzyme and exhibit good stability in storage temperature. 44

45. 2.3 To Promote Transdermal Delivery of Drugs Niosomes enhance the uptake of drugs through the skin. Cosmetics : topics use of niosome entrapped antibiotics to treat acne is done . 2.4 To Improve Anti-inflammatory Activity Niosomal formulation of diclofenac sodium prepared with 70% cholesterol showed greater anti-inflammatory effect as compared to the free drug. Similarly , nimesulide and flurbiprofen showed greater activity than the free drug 45

46. 3.For Targeting and Retention of Drug in Blood Circulation 3.1 For Increased Uptake by A431 Cells [a model cell line ( epidermoid carcinoma) used in biomedical research] Chitosan based vesicles incorporating transferrin and glucose as ligand have been reported. These vesicles bind CoA (co-A) to their surface. Chitosan containing vesicles are then taken up by A431 cells and the uptake was found to be enhanced by transferrin . 3.2 For Liver Targeting Methotrexate was reported to be selectively taken up by liver cells after administration as a Niosomes can also be used as a niosomal drug delivery system. 3.3 To Improve the Efficacy of Drugs in Cancer Therapy Most antineoplastic drugs cause severe side effects Niosomes can alter the metabolism , prolong half life of the drug and decreasing the side effects of the drugs . 46

47. 3.4 In Treatment of Localized Psoriasis In the treatment of localized psoriasis, niosomes of methotrexate taking chitosan as polymer have shown promising results 3.5 In Leishmaniasis The leishmaniasis parasite mainly infects liver and spleen cells. The commonly used drugs, antimonials , may damage the body organ like heart, liver, kidney etc. 47

48. 3.6 Carrier for Haemoglobin Niosomes play an important role as a carrier for haemoglobin . The niosomal haemoglobin suspension was found to give superimposable curve on free haemoglobin curve Usefulness of Niosomes in Cosmetics Elastic niosomes showed increased permeation through the skin which will be beneficial for topical anti-aging application . suitable for skin moisturising and tanning products Niosomes were prepared as possible approach to improve the low skin penetration and bioavailability shown by conventional topical vehicle for minoxidil . 48

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50. Marketed products Lancome has come out with a variety of anti-ageing products which are based on niosome formulations. L’Oreal is also conducting research on anti-ageing cosmetic products. 50

51. REFERENCES Sanjay K. Jain and N.K. Jain Controlled and novel drug delivery system Dr. Rakesh S. Patel niosomes as a unique drug delivery system,www.pharmainfo.net Mithal , B. M., A text book of pharmaceutical formulation, 6 th Edn ., vallabh prakashan , 6, 306-307 International journal of pharmaceutical Science and Nanotechnology volume 1,issue 1, April-June 2008 Shailendra Kumar Singh et.al, Niosomes: A Controlled and Novel Drug Delivery System, Biol. Pharm. Bull. 34(7) 945—953(July, 2011) 51

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