1. NIOSOMES PRESENTED BY: KALYAN POTHAKAMURI M.Pharmacy (Pharmaceutics) 2 ndsemester

2. PRESENTATION FLOW Introduction Methods of Preparation Factors Affecting NiosomesPreparation Stability of Niosomes Applications of Niosomes.

3. Introduction NIOSOMES 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 . These are very small, and microscopic in size that lies in the nanometric scale. Although structurally similar to liposomes, they offer several advantages over them. Niosomes have recently been shown to greatly increase transdermal drug delivery and also in targeted drug delivery.

4. WHY ? WHY? WHY? Used for a variety of drugs : accommodate hydrophilic, lipophilic as well as amphiphilic moieties. Act as a depot to release the drug slowly and offer a controlled release . Osmotically active and stable. Increase the stability of the entrapped drug. Handling and storage of surfactants do not require any special conditions Enhance the skin penetration of drugs

5. Structure of Niosomes Niosomes are microscopic lamellar structures, which are formed on the admixture of non-ionic surfactant of the alkyl or dialkylpolyglycerol ether class and cholesterol with subsequent hydration in aqueous media. Niosomes may be unilamellar or multilamellar depending on the method used to prepare them. The hydrophilic ends areexposed on the outside and inside of the vesicle, while the hydrophobic chains face each other ` within the bilayer. Hence, the vesicle holds hydrophilic drugs within the space enclosed in the vesicle, while hydrophobic drugs are embedded within the bilayer itself. .

6. Contd…

8. Small Unilamellar Vesicle (SUV) Large Unilamellar Vesicle (LUV) Multilamellar Vesicle (MLV) Typical Size Ranges: SLV: 20-50 nm – MLV:100-1000 nm

9. Niosomes Vs Liposomes In both basic unit of assembly is Amphiphiles, but they phospholipids in liposomes and nonionic surfactants in niosomes. Both can entrap hydrophilic and lipophilic drugs. Both have same physical properties but differ in their chemical composition. Niosomes has higher chemical stability than liposomes. Niosomes made of uncharged single chain surfactant molecules Liposomesmade of neutral or charged double chain phospholipids. .

11. Increase the bioavailability

12. Decrease the clearence

13. Used for targeted drug delivery

14. Properties depends on both composition of bilayer and method of preparation.

16. Peroxidation of unsaturated phospholipids.

17. As liposomes have purified phospholipids they are to be stored and handled at inert(N2) atmospheres where as Niosomes are are made of non ionic surfactants and are easy to handle and store.

18. Phospholipid raw materials are naturally occurring substances and as such require extensive purification thus making them costly.

19. Niosomes : Types 1.Bola-Surfactant containing Niosomes: Niosomes made of alpha,omega-hexadecyl-bis-(1-aza-18-crown-6) (Bola-surfactant)-Span 80-cholesterol (2:3:1 molar ratio) are named as Bola-Surfactant containing Niosomes. 2. Proniosomes: A dry product which may be hydrated immediately before use to yield aqueous Niosome dispersions. These ‘proniosomes’ minimize problems of Niosome physical stability such as aggregation, fusion and leaking, and provide additional convenience in transportation, distribution, storage, and dosing. .

20. Formation of niosomes from proniosomes

21. Factors Affecting NiosomesFormation Hydration Temperature Non-ionic surfactant nature Factors affecting niosomes formation Surfactants and lipid levels Membrane additives Nature of encapsulated drug

22. Contd… Nature of non-ionic surfactant Type of surfactant influences encapsulation efficiency, toxicity, and stability of niosomes SURFACTANT Linked via ether , amide or ester bonds Hydrophobic tail Hydrophilic head Consist of one or two alkyl or perfluroroalkyl groups or in some cases a single steriodal group.

24. Uchegbu et al reported that Span surfactants with HLB values between 4 and 8 were found to be compatible with vesicle formation

25. The water soluble detergent polysorbate 20 (HLB value 16.7) also forms niosomes with cholesterol

28. Film method

29. Sonication

30. Reverse phase evaporation

31. The “Bubble” method

33. A mixture of surfactant and cholesterol (150 μmol) is dissolved in ether (20 ml) and injected into an aqueous phase (4 ml) using a 14- gauge needle syringe

34. Temperature of the system is maintained at 60oC during the process

36. The organic solvent is removed by low pressure/vacuum at room temperature

37. The resultant dry surfactant film is hydrated by agitation at 50-60oC

39. Homogenized using a sonic probe

40. The resultant vesicles are of small unilamellar (SUV) type niosomes

41. The SUV type niosomes are larger than SUV liposomes

43. The mixture is sonicated and subsequently chloroform is evaporated under reduced pressure

44. The surfactant first forms a gel and then hydrates to form niosomal vesicles

46. Contd… Micro fluidization This is a recent technique to prepare small MLVS A microfludizer is used to pump the fluid at a very high pressure (10,000 psi) through a 5 pm screen It is then forced along defined micro channels, which direct two streams of fluid to collide together at right angles, thereby affecting a very efficient transfer of energy The lipids/surfactants can be introduced into the fluidizer The fluid collected can be recycled until spherical vesicles are obtained Uniform and small sized vesicles are obtained

47. Contd… Post-Preparation Processes Downsizing Separation of unentrapped material

48. Contd… Probe sonication Size reduction of niosomes Extrusion through filters High-pressure homogenization Combination of sonication and filtration Microfluidization

49. Dialysis Separation of unentrapped material from niosomes Centrifugation Gel filtration Ultracentrifugation

51. Niosomes prepared by ether injection method have better entrapment efficiency than those prepared by the film or sonication

52. Addition of cholesterol to non-ionic surfactants with single- or dialkyl-chain significantly alters the entrapment efficiency

53. Surfactants of glycerol type lead to reduction in entrapment capacity as the amount of cholesterol increases

55. contd… In-vitro release : A method of in-vitro release rate study includes the use of dialysis tubing. A dialysis sac is washed and soaked in distilled water. The vesicle suspension is pipetted into a bag made up of the tubing and sealed. The bag containing the vesicles is placed in 200 ml of buffer solution in a 250 ml beaker with constant shaking at 25°C or 37°C. At various time intervals, the buffer is analyzed for the drug content by an appropriate assay methodof vesicles during the cycle.

58. Nature of encapsulated drug

59. Storage temperature

60. Detergents

61. Use of membrane spanning lipids

64. Slow penetration of drug through skin is the major drawback of transdermal route of delivery. An increase in the penetration rate has been achieved by transdermal delivery of drug incorporated in niosomes. has studied the topical delivery of erythromycin from various formulations including niosomes or hairless mouse.

65. parenteral Applications

66. Niosomes in sub-micron size are used for parenteral administration

68. First application of niosomes as radiopharmaceuticals demonstrated by Erdogan et al. in 1996.

69. Delivery of peptide drugsOral delivery of 9-desglycinamide, 8-arginine vasopressin entrapped in niosomes increase stability of peptide significantly.

70. Contd… Ophthalmic Drug Delivery Saettone et al. (1996) reported on the biological evaluation of a niosomalCyclopentolate delivery system for opthalmic delivery Polysorbate 20 and cholesterol were used for niosomes formulation Optimum pH for peak permation values was pH 5.5, permeatiom decreased at pH 7.4 But in vivo data showed no such dependent on pH Niosomes> 10 μm are suitable for drug administration to eye

72. Phase I and phase II studies were conducted for Niosomalmethotrexate gel in the treatment of localized psoriasis. These studies suggest that niosomalmethotrexate gel is more efficacious than placebo and marketed methotrexate gel.

73. A research article was published that Acyclovir entrapped niosomes were prepared by Hand shaking and Ether injection methods increases the oral bioavailability

75. References 1. Malhotra M and Jain NK. Niosomes as Drug Carriers. Indian Drugs 31 (3), 1994, 81-86. 2. Handjani-Vila RM., Ribier A, Rondot B and Vanlerberghie G. Dispersions of lamellar phases of non-ionic lipids in cosmetic products. International Journal of Cosmetic Science 1 (5), 1979, 303-314. 3. Baillie AJ, Florence AT, Hume LR, Rogerson A, and Muirhead GT ,The preparation and properties of niosomes-non-ionic surfactant vesicles. J. PharmPharmacol. 37(12), 1985, 863–868.

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