recent advances in vesicular drug delivery system.
A SEMINAR ON“RECENT ADVANCES IN VESICULRDRUG DELIVERYSYSTEM”Under the Guidance of,Dr. N. H. ALOORKARM. PHARM. Ph. DPresented by,Mr. N. G. SHINDEM. PHARM. (Sem. II)SATARA COLLEGE OF PHARMACY, SATARA.
4Advantages-Prolongation of existence of drug in systemic circulation.Reduce toxicity.Improved bioavailability.Hydrophilic- Lipophilic drugs can be incorporated.Sustained release system- Delay elimination of rapidly metabolizing drugs.VESICULAR DRUG DELIVERY SYSTEM
5WHY VESICULAR DRUG DELIVERY SYSTEM ? Degradation of drug and/or drug loss. Harmful side effects. Bioavailability at site of disease. Intracellular infection-Conventional therapy is ineffective due to limitedpermeation into cell and the problem can be overcomeby VDDS.
6Microscopic spheres - cholesterol, non-toxicsurfactant, glycolipids etc.Hollow spheres of lipids.Size- 50 nm-150 nm in diameter.LIPOSOMES
7• COMPONENTS-• Phospholipids- Dipalmitoyl phosphatidilcholineDipalmitoyl phosphatidil glycerol(DPPG)• Cholesterol- makes memb. less permeable by filling up holes and disruptionsLipid conjugated dieneMethacrylate and thiol groupCharge induced lipids
9 Suitable for delivery ofhydrophobic, hydrophilic drugs. Biocompatible. Suitable for controlled release. Localized action in particulartissues. Suitable to administer via variousroutes. High production cost. Leakage/ fusion of encapsulateddrug. Phospholipids undergohydrolysis/oxidation reaction.(Ester bonds/Unsat. Acyl gr.) Short half-life & low solubility.ADVANTAGES DISADVANTAGES
10 Immunoliposome Stealth liposome- PEG coating Improve stability & lengthen circulating halflife.Inhibit recognition by RES system. Phospholipids Synthetic Phospholipids Glycerolipids Sphingolipids Glycosphingolipids Steroids Polymeric material Charge-inducing lipidsAdvances in liposomesMaterials used inliposomes preparation
11• The lipid bilayer of the liposome can fuse with otherbilayers (e.g. cell membrane) thus delivering theliposome contents. Endocytosis Adsorption to cell surface Fusion with plasma cellmembrane Transfer of liposomalcontentDrug release from liposomes
15Liposomes as Protein Carriers in Immunology.Oral Drug Delivery.Site Specific Delivery.Sustained or Controlled Delivery.Gene Therapeutics.E.g. Liposomal amphotericin B (Enzon)- Fungal infectionLiposomal morphine (Endo, SkyePharma)- PostsurgicalanalgesiaApplications
Niosomes are non-ionic surfactant vesicles obtained by hydration ofsynthetic non-ionic surfactant with or without incarporation ofcholesterol or other lipids.The vesicle is composed of a bilayer of non-ionic surface activeagents and hence the name niosomes.Higher chemical stability than liposome.NIOSOMES
18Hydrophilic, lipophilic as well as amphiphilic moieties can beincorporated.Act as a depot to release the drug slowly and offer a controlledrelease .Handling and storage of surfactants do not require any specialconditions.Enhance the skin penetration of drugs.WHY NIOSOMES ?
20High patient compliance - oily dosage forms.Accommodate drug molecules with a wide range of solubilities.Stable, increase the stability of entrapped drug.Biodegradable, biocompatible and nonimmunogenic.Given by oral, parenteral and topical routes.Improved oral bioavailability of poorly absorbed drugs.20ADVANTAGES OF NIOSOMES
21Ester bonds of phospholipids are easily hydrolyzed, this canlead to phosphoryl migration at low PH.Peroxidation of unsaturated phospholipids.As liposomes have purified phospholipids they are to be storedand handled at inert(N2) atmospheres where as Niosomes aremade of non ionic surfactants and are easy to handle andstore.Phospholipids are naturally occurring substances and as suchrequire extensive purification thus making them costly.ADVANTAGES OF NIOSOME OVER LIPOSOME
23 Transdermal Applications-An increase in the penetration rate has been achieved by transdermaldelivery of drug incorporated in niosomes.E.g. erythromycin Parenteral Applications- Niosomes -sub-micron size Vesicles up to 10 μm are administered via i.p. or i.m.• Delivery of peptide drugs- Oral delivery of 9-desglycinamide, 8-arginine vasopressin entrapped inniosomes increase stability of peptide significantly.• Ophthalmic Drug Delivery-Niosomes in less size are suitable for drug administration to eye.
24 PEG -glucose conjugates on the surface of niosomessignificantly improved tumor targeting of an encapsulatedparamagnetic agent. Phase I and phase II studies- Methotrexate gel- localized psoriasis. Niosomal methotrexate gel is more efficacious thanplacebo and marketed methotrexate gel.RECENT ADVANCES IN NIOSOMES
25A research article was published claiming that acyclovirentrapped niosomes were prepared by Hand shaking and Etherinjection methods . The results indicated an increase in the oralbioavailability of acyclovir.Lancome has come out with a variety of anti-ageing productswhich are based on niosome formulationsRECENT ADVANCES IN NIOSOMES
26Lipid based elastic vesicles-Phospholipids, alcohol (In high concentration) and water.Size : nanometer- micronsHigh conc. Ethanol- (20-50%)Lipid memb. Packed less tightly than conventional vesicles henceimproved drug distribution through stratum corneum.↑ Fluidity of cell membrane → ↑skin permeabilityUlter solubility properties of stratum corneum↑Solubility of drug,e.g. Levonorgesterol, hydrocortisone, 5-flurouracil (TDDS).ETHOSOMES
28Delivery of large molecules. e.g. peptides, proteins.High patient compliance- (semisolid gel/ cream)Passive, non-invasive and immediate commercialization.Enhanced drug permeation through skin (TDDS).Applied widely in Pharmaceutical, Veterinary, andCosmetic fields.e.g. Antiviral drugs- Zidovudine (orally- side effects)Ethosomal preperation- prolong releaseTDD of harmones- 30 times more permeation of drug.TESTOSOME Patch (Testosterone ethosome) (rabbit pinna skin)Advantages of ethosomal drug delivery
29TRANSFEROSOMESTransferosomes are specially optimized ultra-deformable lipidsupramolecular aggregates which are able to penetrate the skin. It consists of inner aqueous compartment surrounded by lipidbilayer (semidilute suspension). Deformability property- Rapid shape transformationNon-invasive delivery of small, medium and large sizeddrugs.
31High deformability gives better penetration of drug.Acts as carrier for LMW & HMW drugs.e.g. analgesics, sex hormones, anticancer etc.Biocompatible and biodegradable.High entrapment efficiencyUsed for topical, systemic delivery.Easy to scale up.Advantages of Transferosomes
32VESICULARSYSTEMPROBLEMSLiposomes&Transferosomes• Degradation by oxidation, sedimentation, leaching ofdrug• Lack of purity of the natural phospholipids• Expensive to prepareNiosomesAqueous suspension –aggregation, fusion, leaching or hydrolysis ofentrapped drugs, thus limiting the shelf life• Time consuming preparation• Requires specialized equipment.
33(Pharmacon- drug, soma- carrier)System formed by linking the drug to a carrier.Colloidal dispersion of drugs covalently bound to lipids.Self Assembled Nanoparticles (SAN).Composed of amphiphilic prodrugs, so high drug loadingamount & very low drug leakage can be achieved easily.↓interfacial tension-↑ contact area- ↑ bioavailability.PHARMACOSOMES
34ADVANTAGES-Drug targetingControlled releaseHigh entrapment efficiencyNo need of removal of unentrapped drug fromformulation as required in liposome.Improves bioavailability of poorly soluble drugs.Suitable for hydrophilic-lipophilic drugs.Reduce cost of therapy.PHARMACOSOMES
35“Hollow shell microcapsules consist of coagulated or fusedparticles at interface of emulsion droplets”.Control of size allows flexibility in application.Colloidosome membrane offers great potential in controllingthe permeability of entrapped species.Allows selective and timed release.COLLOIDOSOMES
36Water soluble phytoconstituents-e.g. flavonoids, tannins, glycosidic aglycons poorly absorbeddue to large mol. Size /poor lipid solubility- poorbioavailability. Better pharmacokinetic and pharmacodynamic profile thanherbal extracts.Advantages-Enhance absorption of lipid insoluble phytoconstituents.Phosphatidylcholine- Acts as carrier and hepatoprotective.Better stability profile (PTC=PC).HERBOSOME
37“Concentric bilayered vesicle in which aqueous volume is entirelyenclosed with phospholipid bilayer membrane”.“Sphingolipids used in preparation of stable liposome”ADVANTAGES- Provide selective passive targeting totumor tissue.-Flexibility to couple with site specificligands. Increase stability via encapsulation.SPHINGOSOMESHydrolysis-√ Ester linkage- PhospholipidsEther amide linkage- Sphingolipids
38“Layerosomes are conventional liposomes coated with one or moremultiple layers of biocompatible polyelectrolytes in order tostabilize their structure”.Layer by layer coating concept – stabilization of nanosystem.LAYEROSOMES
39Unsaturated fatty acid liposomes are colloidal suspensionscomposed of fatty acid and their ionizable species (soap).Fatty acid vesicles are mixed “fatty acid/ soap vesicle”More stable than liposomes.UFOSOMES
40PROLIPOSOME-Lipid and drug are coatedon a soluble carrier to formfree flowing granulatingmaterial.Controlled releaseBetter stabilityIncreased solubilityEase of handlingPRONIOSOMES-Water soluble carrier particlesthat are coated with surfactant.Dry & free flowing product.More stable during sterilizationand storage.Minimizes problems of niosomessuch as fusion, aggregation,sedimentation, leakage on storage.STRATEGIES TO IMPROVE INTRAVESICLE DRUG DELIVERYPROVESICULAR DRUG DELIVERY
41Physical means-IONTOPHORESIS-effective method of drug transport in deeper layer of bladder.e.g. Mitomycin C , BethanecholElectroporation (high voltage than Iontophoresis)↑ Permeability of tissue due to electric field.Helpful for delivery of drug in bladder carcinoma treatment.Electroporation- Sonophoresis (low intensity ultrasound waves)-↓ tissue damage.STRATEGIES TO IMPROVE INTRAVESICLE DRUG DELIVERYIMPROVING PERMEABILITY
42Chemical means-Prior instillation of DMSO enhance absorption ofchemotherapeutic drugs.e.g. Paclitaxel, PirarubicinIntravesicle instillation of saponin before administration ofanticancer drug.e.g. 4-0-tetrahydropyranyldoxorubicin (THP)↑ Conc. of THP in bladder tissue.Topical application of Chitosan and Cyclodextrins- disruptsintercellular tight junction- ↑paracellular transport.STRATEGIES TO IMPROVE INTRAVESICLE DRUG DELIVERY
45AQUASOMES“Three layered self assembly - ceramics carbon nanocrystallineparticulate core coated with glassy cellobiose -specific targeting &molecular shielding”.CRYPTOSOMES“Lipid vesicles with surface coat composed of pc and of suitablepolyoxyethylene derivative of phosphatidyl ethanolamine”.Capable of ligand mediated drug targeting.DISCOMES“Niosome solubilized with non-ionic surfactant solution”.(polyoxyethylene cetyl ether class)
46EMULSOMES“Nanosize lipid particles (bioadhesive nanoemulsion) consist ofmicroscopic lipid assembly with polar core used for parenteraldelivery of poorly water soluble drugs”.GENOSOMES“Artificial macromolecular complexes for functional genetransfer.”Cationic lipids-↑biodegradability & stability in blood stream.PHOTOSOMES“Photolyses encapsulated in liposome, which release the contentphoto-triggered charges in membrane permeabilitycharacteristics”
47VIROSOME“Liposome spiked with virus glycoprotein, incorporated intothe liposomal bilayers based on retro virus derived lipids”.VESOSOMES“Nested bilayer compartment of saturated phospholipids”.Multiple compartments- better protection to the interiorcontents .PROTEOSOMES“High molecular weight multi-submit enzyme complexes withcatalytic activity, specifically due to the assembly pattern ofenzymes”.
48HEMOSOMES“Hb containing liposome engineered by immobilizing Hb withpolymerizable phospholipids”.ERYTHROSOMES“Liposomal system in which chemically cross linked humanerythrocytes cytoskeletons are used as support to which lipidbilayer is coated”.ENZYMOSOMES“Enzymes are covalently immobilized or coupled to thesurface of liposomes”.
49Saurabh Bansal, A comparative review on vesicular drug delivery system andstability issues, IJRPC, 2012, 704-715.Patel j. k, Aquasomes: a self-assembling nanobiopharmaceutical carrier system forbioactive molecules: a review, IJPRS(2), 2012, 11-21.Mayank Gangwar, Recent advances in various emerging vesicular systems: anoverview, APJTB, 2012, S1177-S1188.Seema M. Jadhav, Novel vesicular system: an overview, JAPS (01); 2012,193-202.Nishith Patel, Liposome Drug delivery system: a Critic Review, JPSBR(2), 2012,169-175.REFERENCES
50Sreedevi A, A Pharmacosomes – a review, IJPR (12), 2012; 114-117.N. Bharti, Proniosomes: a recent advancement in nanotechnology as a drugcarrier, IJPRD, 2012(12), 67-75.Deepthi Annakula, „Provesicular drug delivery systems: An overview andappraisal, AASR(4), 2010, 135-146.Kombath Ravindran Vinod, Critical issues related to Transferosomes – NovelVesicular System, ASPTA (1) 2012, 67-82.REFERENCES