Microfluidics as a bottom up technique for drug · Microfluidics as a bottom‐up technique for...
Transcript of Microfluidics as a bottom up technique for drug · Microfluidics as a bottom‐up technique for...
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Microfluidics as a bottom‐up technique for drug delivery nanoparticles
Maria Helena A. Zanin and Mario R. Gongora‐Rubio
Center for Process and Products Technology
Chemical Processes and Particle Technology Laboratory
CTPP‐LPP
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Summary
Particle and encapsulation technology at IPT
Technological solutions to active encapsulation
Microfluidics
Microfluidics as a bottom‐up nanofabrication technique
Current work in microfluidics at IPT
Technological perspectives
Technology team
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ActivesActives
drugs, fragrances, flavours, minerals,
vitamins, colorants, pesticides
Objectives
Controlled release or not
Protection against external agents
Reduction of losses to the environment
Others
Encapsulation ?
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FOOD
INDUSTRY
TEXTILE INDUSTRY
COSMETIC INDUSTRY
PHARMACEUTICAL INDUSTRY
AGROCHEMISTRYINDUSTRY
Encapsulation: Technology of industrial interest
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How to choose the encapsulation technique?
Points to be considered
Active agent
Polymer
Physical and phisico‐chemical property of active and polymer
Compatibility of polymer and active
Route of active agent delivery
Scalable process
Cost
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Spray drying
Coacervation
Emulsion/solvent extraction
Gelification
Polymerisation
Electrospinning
Microfluidics
Technology
Micro‐nanoencapsulation at IPT
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Technological solutionTechnological solutionss to to active encapsulation at IPTactive encapsulation at IPT
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Spray‐dryerMicroencapsulation of poliminerals to the food industry
PPrrevious work: Industrial and governmentevious work: Industrial and governmentalal fundingfunding
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Complex coacervation
Microcapsules containing vitamin to the cosmetic application
Previous work: Industrial funding
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Emulsification and solvent evaporation
Study of nanocarries to encapsulate drug to application in fotodynamic therapy of
cancer
Current project: government funding (FAPESP/IPT)Current project: government funding (FAPESP/IPT)
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dissolved
dispersed80%PHBHV-20%PEG
80%PHBHV-20%PLA
2000x
Emulsification and solvent evaporationVitamin encapsulationVitamin encapsulation
Previous work: Industrial and government fundingPrevious work: Industrial and government funding
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Emulsification ‐ solid lipidic nanoparticlesDevelopment of nanocarries based on wax to encapsulate Development of nanocarries based on wax to encapsulate benzophenonebenzophenone‐‐33 to cosmetic to cosmetic application. Previous work: Doctorare thesisapplication. Previous work: Doctorare thesis
Government funding Government funding ‐‐ CNPqCNPq
H2O + Surfactant(85± 5°C)
Agitation Buffer solution 7.4 (5% Tween 80)
Active+melted Lipid (85± 5°C)
High pressure homogeneizer (HPH)
(600bar)
Franz diffusion cell
HPLC
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Interfacial polimerization
Micro/nanocapsules containing pesticides to the veterinary and agrochemical
application. Previous work: Industrial fundingPrevious work: Industrial funding
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Emulsification and solvent difusion
Thermosensitive nanoparticle to carry actives
Previous work: Doctorate thesis Previous work: Doctorate thesis ‐‐ Government funding Government funding –– FAPESP/IPT FAPESP/IPT –– Patent Patent
number. PI 0902050number. PI 0902050‐‐00
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Electrospinning
Development of nanofibers by electrospinning process using biocompatible polymer
to incorporate drugs. Current project: Government funding : Government funding –– CNPq/IPTCNPq/IPT.
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B.K. Paul, PNNL,2004
Microfluidics applications
Microreactors for:• Transesterification (Biodiesel)• Reformers•Catalytic material screening •Hydrogenation
Microreactors for:•Microcrystallization• NanoPrecipitation•Micro‐Nano Encapsulation
• MicroFluidics for water treatment
and Microsensors
•Biosensors
• Micromixers • Continuous separators• Micro‐destillation• Heat exchangers
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Definition
Microfluidic is a science of designing and manufacturing devices in a microscale , dealing with volumes of fluids on order of nanoliters or picoliters.
Using microfabrication techniques is possible to manufacture devices in materials such as silicon, glasses, polymers and ceramics.
Advantages such as low reagents and energy consumption, portability and safety are feasible In the microscale.
Microfluidic devices have applications in Pharmaceutics, Chemical Analysis, Chemical Processes and Food Engineering.
Microfluidics
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Laminar Flow – Low Reynolds Number;
Surface forces are dominant over volume forces;
Capillarity and interface phenomena are present over inertial and gravitational phenomena;
Mass transfer are dominated by diffusion.
Microfluidics
Physical characteristics
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Microfluidics as bottom‐up technique
Bottom‐up or Top‐down ?
Bottom-upTop-down
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Microfluidic utilization for particle morphological control
R. K. Shaha, et al. Materials Today, vol 11, number 4, April 2008.
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Scale out in microfluidics
Microfluidics scaling of production is obtained by using the same devices in parallel.
Scale-Up Scale-out
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Microprocesses Nanoparticles
By combining geometry design of microchannels and fluid flow rate is possible to obtain particles with high size control, reproducibility and low polidispersivity.
Microfluidics is a powerful tool to obtain particles in micro and nanoscale and for encapsulate drugs based on:
Emulsions (simple & double)
Liposomes
Nanocrystals
Microfluidics
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EmulsionsBatch Vs Continuous
Microfluidic devices Mineral Oil
Mineral Oil
Polymeric Solution
Drop Outlet
Mineral Oil
Polymeric Solution
Droplet Oulet
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Current works in Current works in microfluidics at IPTmicrofluidics at IPT
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Emulsion generators using glass devices
Simple emulsion production (Water-oil) and droplet size Vs. input flow ratio
J. N. Schianti, et al. Emulsion production using glass microfluidic devices, Proc: IBERSENSOR 2010
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(DCM/BD1/Q36)
Micrographs of PLGA (Poly (DL‐lactide co‐glycolide) ) microspheres containing BSA (Bovine serum albumin ) ( 750x)
Micro and nanoparticles with micromixers
0
20
40
60
80
0 50 100 150 200 250Time (hours)
Rel
ease
d B
SA (%
)
Micromixer ED2 Micromixer BD1 Conventional mechanical agitation
M. Ribeiro‐Costa, et al. Preparation of protein‐loaded‐PLGA microspheres by an emulsion/solvent evaporation process employing LTCC micromixers, Powder Technology Vol‐190, p.107–111, (2009)
Comparison between Turrax agitation and micromixer particles obtained using micromixers.
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BOTTOM - UP
Liposome
Microfluidic Hydrodynamic Focusing
Nanoliposome production via microfluidics
J. N. Schianti, et al. Glass flow focusing microfluidic device for nanoliposome production, Proc: IBERSENSOR 2010
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BOTTOM - UP
Nanocrystals
Microfluidic Flow Focusing
Crystallization process to obtain rifampicin amorphous nanoparticles
Nanocrystallization process by microfluidics
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Technological perspectives
Microfabrication of unit operation devices for chemical process intensification, including synthesis of micro and nanoparticles for feasible products.
Microfabrication of devices adapted to the encapsulation process in order to design capsule or emulsion with size and morphology controlled in continuous process.
Introduction of new microfluidic techniques for production of drug delivery nanostructured particles.
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Technology TeamCTPP ‐ Director Dr. Maria Filomena de A. Rodrigues ([email protected])
LPP Laboratory headDr. Wagner Aldeia ([email protected])
Researcher (PhD) 8Researcher (MSc.) 1Researcher 6 Laboratory technicians 5
StudentsPhD student 3Post Doctorate 1
Thank you for your attention!!!