What is Nanotechnology?
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1 Use of Nanotechnology to Optimize Delivery of Probiotics and Prebiotics to Target Sites Ian G Tucker Professor of Pharmaceutical Sciences University of What is Nanotechnology? Some people say they have been doing nanotech for years colloid scientists Stained glass windows in medieval churches contain different sized gold nanoparticles Einstein estimated the size of a sugar molecule as 1 nm
2 What is Nanotechnology? Current nanoscience has an aggressive focus on developing applied nanotechnologies National Nanotechnology Initiative Nanotechnology involves research and technology development at the nm range Nanotechnology creates and uses structures that have novel properties because of their small size Nanotechnology builds on the ability to control or manipulate at the atomic scale What approaches can we use to control and manipulate delivery of prebiotics and probiotics to various places in the gastrointestinal tract?
3 Increasing the Efficacy of Probiotics through Formulation and Delivery Increasing survival in the stomach Delivery to the colon Co-delivery of pre and probiotics Targeting the mucosa (Survival during technological processing and storage - not covered) (Strain selection not covered) Increasing the Efficacy of Probiotics through Formulation and Delivery Increasing survival in the stomach
4 Increasing Survival in the Stomach Duodenum ph 6 Esophagus Stomach ph rising to ph 5 after a meal Jejunum & Ileum (small intestine) : ph Colon ph 6.0 Gastric Residence Times Fed versus fasted Tablets versus pellets
5 Residence Times of Tablets in the Stomach Continuous eating Fasted Residence Times of Pellets and Tablets in the Stomach
6 J.Microbiol Methods 2004 Calcium chloride bath um Uniform beads Survival of L acidophilus Encapsulated in ph2 Free in ph2 Release of L acidophilus from microcapsules into ph 7 buffer of various molarities
7 J.Microbiol Methods 2004 Calcium chloride bath um Uniform beads A Novel Scalable Method for Crosslinked Alginate Matrices Stirrer Granule in Calcium Chloride bath Untreated Granule Crosslinked granule Granule prepared by high shear Surface Morphology X-linking
8 Eudragit polymers Increasing the Efficacy of Probiotics through Formulation and Delivery Increasing survival in the stomach Targeting the colon
9 Methods of Targeting Release in the Colon Time-controlled release ph-triggered release Enzyme-triggered release Time-controlled systems to target the colon Duodenum Esophagus Stomach Stomach transit time is variable Colon Jejunum & Ileum (small intestine) : Small intestinal transit time = 3-5h
10 Triggered time-controlled Release
11 From Gazzaniga, 2005 Methods of Targeting Release in the Colon Time-controlled release ph-triggered release
12 Polymethacrylate Polymers The intestinal ph is relatively constant From Shalsky, 2005
13 ph-triggered release in the distal small intestine Dissolves in distal Small intestine
14 Methods of Targeting Release in the Colon Time-controlled release ph-triggered release Enzymatic-triggering of release
15 Azo-polymer coated insulin capsules dosed orally to diabetic rats Saffin et al, 1986 Glassy Amylose Resistant to salivary and pancreatic amylase Degraded by colonic bacterial amylase Cornflakes contain 15-20% glassy amylose Has film forming properties Glassy amylose coated prednisolone pellets in Phase III trial
16 Amylose (A) Ethylcellulose (EC) Mixed Film Correlation between Arrival of A-EC Coated Pellets and Drug In Blood
17 Increasing the Efficacy of Probiotics through Formulation and Delivery Increasing survival in the stomach Targeting the colon Co-delivery of pre and probiotics
18 Controlling the Physical Properities and Yield of the Product Variables: Inlet temp. 110 C Aspirator 100% Q-Flow 17 Nozzle Cleaner 5x Pumprate 5% Buchi Mini Spray Dryer B-290 Outlet temp C Yield 31,6-54,45% SEMs of Microparticles produced by Spray Drying 1µm 0 % Eudragit 15 % Eudragit 30 % Eudragit 50 % Eudragit
19 Survival during Spray Drying Stationary > Lag Survival during Storage under various conditions Corcoran et al 2004 Prebiotic did not increase stability on spray drying or on storage Increasing the Efficacy of Probiotics through Formulation and Delivery Increasing survival in the stomach Delivery to the colon Co-delivery of pre and probiotics Targeting the mucosa
20 Mucoadhesive Dosage Forms 20 µm Go Nano Go Macro 200 nm 1 cm
21 Go Macro but think Nano Pre and probiotics can be combined in the formulation Granules can be coated with a colonic polymer to target release in the colon A bioadhesive polymer (specific) can be included to promote adhesion to the gut wall (mucus) possibly to promote colonisation Colonic polymer coating Pre & probiotic Bioadhesive polymer 1-2 mm 10 th Annual Conference on Fomulation and Delivery of Bioactives Feb 2008
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