Niosomes as Drug carrier (Novel Drug Delivery system)

Niosomes - Classification,
Composition, Preparation
Methods of Preparation, Separation of unentrapped drugs, Liposomes Vs. Niosomes
Evaluation of niosomes
Applications of Niosomes

1. PRESENTATION Topic- Niosomes Mentor: Dr. Rekha Rao (Assistant Professor) Deptt . Of Pharmaceutical sciences GJUS&T, HISSAR Presented By: Himanshu N aphria M .Pharmacy 2 st Sem(Pharmaceutics) R oll no. 230121220011

2. Table of Content: Novel Drug Delivery system ? Niosomes ? General Characteristics Of Niosome Classification of Niosomes Composition of Niosomes General Steps of Niosome Preparation Methods of Preparation Separation of unentrapped drugs Liposomes Vs. Niosomes Evaluation of niosomes Applications of Niosomes References

3. Novel Drug Delivery system? Novel Drug delivery System ( NDDS ) refers to the approaches, formulations, technologies, and systems for transporting a pharmaceutical compound in the body as needed to safely achieve its desired therapeutic effects . Carriers Of Novel Drug Delivery System? A carrier-based drug delivery system implies that drug molecules will be loaded into vesicular and/or polymeric system. Some examples of these carriers are polymeric micelles, liposomes , Niosomes , dendrimers , and nanoparticles.(NPs) Nanocarriers present a great approach in drug delivery with promising features such as protection of drug from degradation and cleavage, controlled release, and in case of targeted delivery approaches the delivery of drug molecules to the target sites. 1.

4. Niosomes ? Niosomes are one of the promising drug carriers that have a bilayer structure and are formed by self-association of nonionic surfactants and cholesterol in an aqueous phase . They have long shelf life, exhibit high stability, and enable the delivery of drug at target site in a controlled and/or sustained manner. General Characteristics Of Niosome : Biocompatible , biodegradable, non-toxic, non immunogenic and non- carcinogenic. The niosomes are very small, and microscopic in size. Their size lies in the nanometric scale. High resistance to hydrolytic degradation. Niosome can act as carrier for both hydrophilic and lyophilic drug. Fig: 3D representation of N iosome 2.

5. Classification of Niosomes : The niosomes are classified as a function of the number of bilayer (e.g. MLV, SUV) or as a function of size. (e.g. LUV, SUV)The various types of niosomes are described below : i) Multi lamellar vesicles (MLV, Size=>0.05 µm) ii) Large unilamellar vesicles (LUV, Size=>0.10 µm). iii) Small unilamellar vesicles (SUV, Size=0.025-0.05 µm) 3.

6. Composition of Niosomes : Cholesterol and non-ionic surfactants are the two major components used for the preparation of niosomes . Cholesterol provides rigidity and proper shape . The surfactants play a major role in the formation of niosomes . Non-ionic surfactants like span ( span 20, 40, 60, 85, 80), tweens (tween 20, 40, 60, 80) and brij ( brij 30, 35,52,58 52.26) are generally used for the preparation of niosomes . A few other surfactants that are reported to form niosomes are as follows . Ether-linked surfactant Dialkyl chain surfactant Ester linked Sorbitan esters Polysorbates 4

7. General Steps of Niosome Preparation: Hydration of mixture of surfactant/lipid at elevated temperature. Sizing of niosomes . Removal of unentrapped material from vesicles. Common Stages of all Methods of Preparation of Niosomes : Dissolve in organic solvent Drying Dispersion ( hydration) 5.

8. Ether-Injection method : This method is based on slow injection of surfactant:Cholesterol solution in ether through gauge needle into a preheated aqueous phase maintained at 60°C. Vaporization of ether resulting into a formation of ether gradient at ether-water interface which leads to formation of single-layered vesicles . Depending upon the conditions used the diameter of the vesicle range from 50 to 1000 nm . Methods of Preparation: 6.

9. 2. Hand-shaking method : (Thin Film Hydration Technique ) Surfactant and cholesterol are dissolved in a volatile organic solvent (diethyl ether, chloroform or methanol) in a round bottom flask. The organic solvent is removed under vacuum at room temperature using rotary evaporator leaving a thin layer of solid mixture deposited on the wall of the flask. The dried surfactant film can be rehydrated with aqueous phase at temperature slightly above the phase transition temperature of the surfactant used, with gentle agitation. This process forms large multilamellar niosomes . 7.

10. 3. The Bubble Method : It is novel technique for the one step preparation of liposomes and niosomes without the use of organic solvents. The bubbling unit consists of round bottom flask with three necks positioned in water bath to control the temperature. Water-cooled reflux and thermometer are positioned in the first and second neck and nitrogen supply through the third neck. Cholesterol and surfactant are dispersed together in this buffer(pH 7.4 ) at 70°C, the dispersion mixed for 15 second with shear homogenizer and immediately afterwards bubbled at 70°C using nitrogen gas. 8.

11. 4. Reverse Phase Evaporation Technique (REV ): Reverse-phase evaporation technique uses a mixture containing surfactant and cholesterol in a 1:1 ratio, in addition to ether and chloroform. An aqueous phase containing the target drug is added to the mixture followed by sonication at 4-5°C. Sonication is continued after adding a small amount of phosphate-buffered saline to the mixture. The organic solvent is removed at 40°C under a low pressure, and the remaining suspension is diluted with phosphate- buffered saline . After heating the mixture at 60°C for 10 min, the final product of niosomes is obtained.

12. 5 . Multiple membrane extrusion method : I n this method, a mixture of surfactant, cholesterol and diacetyl phosphate is prepared and then solvent is evaporated using rotary vacuum evaporator to leave a thin film. The film is then hydrated with aqueous drug solution and the suspension thus obtained is extruded through the polycarbonate membrane (mean pore size 0.1 mm) and then placed in series up to eight passages to obtain uniform size niosomes . Good method of controlling niosome size. 9.

13. 6 . Sonication : In this method, an aliquot of drug solution in buffer is added to the surfactant/cholesterol mixture in a 10 ml glass vial. The mixture is probe sonicated at 60°C for 3 minutes using a sonicator . The resultant vesicles are of small unilamellar type niosome . 10.

14. Separation of unentrapped drugs: The removal of unentrapped solute from the vesicles can be accomplished by various techniques, which include : 1. 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 . 2. Dialysis : The aqueous niosomal dispersion is dialyzed in a dialysis tubing against phosphate buffer or normal saline or glucose solution. 3. 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. 11.

15. Liposomes Niosomes Vesicles made up of concentric bilayer of phospholipids. Vesicles made up of surfactants with or without incorporation of cholesterol. Size ranges from 10-3000nm. Size ranges from 10-100nm. Comparatively expensive. Inexpensive. Special storage condition are required. No such special requirement. Phospholipids used are unstable. Non-ionic surfactants are stable. Comparatively more toxic. Less toxic. Liposomes Vs. Niosomes 12.

16. Evaluation of niosomes : Vesicle Diameter: Vesicle size can be measured by using optical microscope with a calibrated eyepiece micrometer. The vesicle size of 100 niosomes is measured individually for all batches & its mean value is calculated. Drug Content: Niosomal suspension equivalent to 10mg taken in a volumetric flask of 100ml & volume was made up by phosphate buffer pH 7.4, after that 1ml of this mixture was diluted to 10ml by phosphate buffer 7.4 & the % drug content was calculated or observed at using UV spectrophotometer. Entrapment Efficiency: After preparing Niosomal dispersion, un-entrapped drug is separated by- Dialysis or using Centrifugation. 13.

17. In Vitro Drug Release: It can be determine by membrane diffusion technique. A dialysis sac is washed and soaked in distilled water. The vesicle suspension is pipetted into a bag and sealed. The bag containing the vesicles is placed in 200ml of buffer solution 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 method . Stability Studies: Optimized formulation preserved at refrigerated temperature & room temperature for 30days. After 30days shape, % drug remaining & % entrapment efficiency of vesicles were measured. The results were compared with the initial shape, % drug remaining & % entrapment efficiency of both samples . All stability studies are done according to ICH Guidelines. 14.

18. Applications of Niosomes : Ophthalmic drug delivery: From ocular dosage form like ophthalmic solution, suspension and ointment it is difficult to achieve excellent bioavailability of drug due to the tear production, impermeability of corneal epithelium, non-productive absorption and transient residence time. But niosomal and liposomal delivery systems can be used to achieve good bioavailability of drug . Localized Drug Action: Drug delivery through Niosomes is one of the approaches to achieve localized drug action, since their size and low penetrability through epithelium and connective tissue keeps the drug localized at the site of administration. Localized drug action results in enhancement of efficacy of potency of the drug and at the same time reduces its systemic toxic effects e.g. Antimonials encapsulated within niosomes are taken up by mononuclear cells resulting in localization of drug, increase in potency and hence decrease both in dose and toxicity. 15.

19. Transdermal delivery of drugs by niosomes : An increase in the penetration rate has been achieved by transdermal delivery of drug incorporated in niosomes as slow penetration of drug through skin is the major drawback of transdermal route of delivery for other dosage forms . For Improvement of Stability of Peptide Drugs: The in vitro release of insulin from niosomes formulated by span 40 and span 60 in simulated intestinal fluid was lower than the niosomes formulated by span 20 and span 80. Niosomes prepared by the span 60 has high resistance against proteolytic enzyme and exhibit good stability in storage temperature. 16.

20. The use of liposomes or niosomes in cancer chemotherapy can be attributed to the following properties: ( a) They prolong drug effect due to longer circulation time than with non-encapsulated drugs. (b) They are sequestered as particles to the target tumor location. (c) Toxicity is reduced. (d) Drugs are protected from metabolism and immune attack until they reach their targets . ( e) They are confined to a chosen anatomical compartment . ( f) They are directed to target cells by attaching an antibody or other ligand . ( g) They are directed to their natural targets such as the phagocytic cells or liver, spleen and other organs . (h) Therapeutic effects are amplified by incorporation of numerous drug molecules in each target directed particles. (i) Selective local release from carrier is a function of physical factor such as the local temperature or pH . 17.

21. References : “Textbook on Novel Drug Drug Delivery System” “ Md Rafiul Haque ” CBS Publishers & Distributors P vt Ltd. ( Pg no. 97-104) Textbook of Pharmaceutics By “ N.K Jain” ( Pg no. 291-301) https://www.slideshare.net/AnilPethe/niosomes-107155223

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