固体脂质体纳米粒课件

1、Solid lipid nanoparticles: an oralbioavailability enhancer vehicleName : Li JingMajor : pharmaceuticsMentors : Doctor ChenContents523451Preparation of cryptotanshinon-loaded SLNsOptimization of oral SLNs IntroductionAbsorption of drug-loaded SLNs ConclusionBackground oral routenanoparticulate system

2、s. Liposomes NanoemulsionsPolymeric nano-particles.Nanosuspensionsadvantages disadvantages poor oral BADescription of the contentsDescription of the contentsSLNsPoor oral bioavailability (BA)Poor solubilityHepatic first-pass metabolismNanoparticles (NPs) are considered as alternatives to various con

3、ventional drug delivery techniques .poor oral bioavail-abilityPoor permeabilitySLNsSLN are particles made from solid lipids (i.e. lipids solid at room temperature and also at body temperature and stabilised by surfactant(s) which diameter are between approximately 50 and 1000 nmimproved oral BAof dr

4、ugsImproved stabilityof drugs entrappedin SLNsreduced toxicityreduced multidrug resistance(MDR)4.polymorphic state of lipid material.3. chemical and physical structure of solid lipid matrix;1. solubility of drug in melted lipid;2.miscibility of drug melt and lipid melt;01 03 0204FactorsFactors deter

5、mining the loading capacityYour TextYour TextYour TextYour TextThe development of SLNYour TextYour TextYour Text199019911995 2012The first experiments in the production of lipid nanoparticles were performed in academic labs. They were followed by two independent patent applications and the first pub

6、lications appeared shortly afterwards The first basic review about SLN)appeared which gave an overview of research groups active in this new fieldTheir results are reviewed which cover many different administration routesMethods of preparation of SLNs Methods of preparation of SLNsUltrasonicationhig

7、h-shear homogenization (HSH)The other methodsHigh pressure homogenization (HPH) Analytical characterization of SLN 3. co-existence of additional colloidal structures and dynamic phenomena.1. particle size and zeta potential;2. degree of crystallinity and lipid modication;Mechanism of absorption of d

8、rug-loaded SLNsFigure 2 A. paracellular absorption, B. M cell uptake via Peyer s patches , C. chylomicron- assisted enterocytes absorption. Different shapes of SLNs represent different drug incorporation modelsFigure 4. Absorption of NPs by oral route from a different segment of the GIT. Figure indi

9、cates possible absorption mechanisms and extent of NP absorption from different regions of GITFactors affecting absorptions of SLNs through GIT smaller particles show greater absorption while larger particles are retained for longer duration in the Peyer s patchesmechanistic absorption particle size

10、surface propertieshydrophobicitysurface chargeThe optimization of oral SLNsLipidsEmulsifiersMiscellaneous.include drug properties, methods of Preparationhomogenization relatedparameters and solvents.The various parameters that influence the absorption and stability of SLNs in vivo are discussed as f

11、ollows:LipidsRa domska- Soukharev (2007) demon strated that the selection of lipid excipients was dependent on chemical stability of excipients itself and SLNs stability. . velocity of lipid crystallization lipid hydrophilicity shape surface area source of chemicals melting point Lipids EmulsifiersB

12、y changing the nature andconcentration of the stabilizing emulsifier, gelation after a certain period of storage time can be avoidedProper selection and concentration of emulsifier does not only stabilize but also increases the entrapment efficiency of drug in SLNscharge developed on the surface of

13、theSLNs by emulsifier may also affect the drug release and stability of SLNsCrystallization of lipid is a major phenomenon duringthe emulsification process . However, use of emulsifier could slow down this process1 2 3Increase the stability of SLNs after peroral administration To avoid generation of

14、 an unstablemetastable formof SLNs, the cooling rate and stabilizer play Important roles.when stored atrefrigeratedtemperature were found tobe more stablethan room tem-peraturestorage. Shorter chainlipids Showedhigher degrada-tion while thelonger chain lipids showedslower degrada-tion rate. By using

15、 bilesalts, it waspossible toincrease thestability, butstill it showedtime-dependentaggregation.temperaturenature of the lipid matrix Bile saltsThe stability of SLNs after peroral administrationCooling rate and stabilizerApplications of SLNs by oral routeTable2. Example of drugs showing improved ora

16、l BA upon encapsulation in SLNs.An example Preparation and Enhanced Oral Bioavailability of Cryptotanshinone-Loaded Solid Lipid NanoparticlesTitleMaterialsPreparationResultsDiscussionPreparation of CTS-SLNsThe water phase was addeddropwise to the organic phase with magnetic stirring for5 minAfter th

17、e organic solvent had completelyevaporated, the coarse emulsion was passed through a highpressure homogenizer at 800 bar for three homogenizationcycles.CTS-SLNs were prepared with an ultrasonic and high-pressure homogenization method.Coarse premix was subjected to ultrasonictreatment for 10 min usin

18、g a high-intensity probe ultra-sonicator at 80C. Experimental result TEM shows that the particles had round and uniform shapes. Using soy lecithin alone can produce SLNs with a size above 400nm. The addition ofTween 80 can effectivelydecrease the sizeThe mean diameters of GMS-SLNs and CP-SLNs were12

19、1.4 6.3 nm, 137.5 7.1 nm, The zeta potential ofGMS-SLNs and CP-SLNs were25.2 1.3 mV,27 .6 1 .2 mV,ABCFig. 6. Mean plasma concentrationtime curves after oral admin-istration of CTS at a dose of 16 mg/kg to rats GMS-SLNs(without SD), CP-SLNs (without SD), and CTS-suspension ( n =6)Fig. 7. Mean plasma

20、concentrationtime curves after oral admin-istration of CTS-CP-SLNs containing different amount of SD at aCTS dose of 16 mg/kg (n =6)Discussion1 The decreased metabolism of CTS may be attributed to the protection of the drug from metabolism by embedding the drug into a solid lipid matrix or the interference with intestinal efflux thereby delaying the in viv