Microfluidicsasabottomuptechnique

fordrugdeliverynanoparticles

MariaHelenaA.ZaninandMarioR.GongoraRubio
CenterforProcessandProductsTechnology
ChemicalProcessesandParticleTechnologyLaboratory
CTPPLPP
Summary

ParticleandencapsulationtechnologyatIPT
Technologicalsolutionstoactiveencapsulation
Microfluidics
Microfluidicsasabottomupnanofabrication
technique
CurrentworkinmicrofluidicsatIPT
Technologicalperspectives
Technologyteam
 Encapsulation?

Objectives
Controlledreleaseornot

Protectionagainstexternalagents

Reductionoflossestotheenvironment

Others

Actives
drugs,fragrances,flavours,minerals,
vitamins,colorants,pesticides
Encapsulation:Technologyofindustrialinterest

FOOD
INDUSTRY

COSMETIC TEXTILE
INDUSTRY INDUSTRY

PHARMACEUTICAL AGROCHEMISTRY
INDUSTRY INDUSTRY
 Howtochoosetheencapsulationtechnique?

Pointstobeconsidered
Activeagent

Polymer

Physicalandphisicochemicalpropertyofactiveandpolymer

Compatibilityofpolymerandactive

Routeofactiveagentdelivery

Scalableprocess

Cost
MicronanoencapsulationatIPT

Technology
Spraydrying

Coacervation

Emulsion/solvent
extraction

Gelification

Polymerisation

Electrospinning

Microfluidics
Technologicalsolutions to
activeencapsulationatIPT
Spraydryer
Microencapsulationofpolimineralstothefoodindustry
Previouswork:Industrialandgovernmental funding
 Complex coacervation
Microcapsulescontainingvitamintothecosmeticapplication
Previouswork:Industrialfunding
 Emulsificationandsolvent evaporation

Study of nanocarries to encapsulate drug to application in fotodynamic therapy of

cancer
Currentproject:governmentfunding(FAPESP/IPT)
Emulsificationandsolvent evaporation
Vitaminencapsulation
Previouswork:Industrialandgovernmentfunding

80%PHBHV-20%PLA
dissolved

80%PHBHV-20%PEG
dispersed 2000x
 Emulsification solidlipidic nanoparticles
Developmentofnanocarriesbasedonwaxtoencapsulate benzophenone3 tocosmetic
application.Previouswork:Doctorarethesis
Governmentfunding CNPq
Active+melted
Lipid(85 5C)

HPLC
Franzdiffusion
cell Buffersolution7.4
Agitation
H2O+Surfactant (5%Tween80)
(85 5C)

Highpressure
homogeneizer(HPH)
(600bar)
Interfacialpolimerization

Micro/nanocapsules containing pesticides to the veterinary and agrochemical

application.Previouswork:Industrialfunding
Emulsificationandsolventdifusion
Thermosensitivenanoparticletocarryactives
Previouswork:Doctoratethesis Governmentfunding FAPESP/IPT Patent
number.PI09020500
Electrospinning

Developmentofnanofibersbyelectrospinningprocessusingbiocompatiblepolymer
toincorporatedrugs.Currentproject:Governmentfunding CNPq/IPT.
CNPq/IPT
Microfluidicsapplications

Microreactorsfor: Microreactorsfor:
Microcrystallization Transesterification(Biodiesel)
NanoPrecipitation Reformers
MicroNanoEncapsulation Catalyticmaterialscreening
Hydrogenation

Biosensors

Micromixers
Continuousseparators
Microdestillation
MicroFluidicsfor Heatexchangers
watertreatment
and
Microsensors

B.K. Paul, PNNL,2004

Microfluidics

Definition
Microfluidicisascienceofdesigningandmanufacturingdevicesin a
microscale , dealing with volumes of fluids on order of nanoliters or
picoliters.

Usingmicrofabricationtechniquesispossibletomanufacturedevicesin
materialssuchassilicon,glasses,polymersandceramics.

Advantages such as low reagents and energy consumption, portability

andsafetyarefeasibleInthemicroscale.

Microfluidic devices have applications in Pharmaceutics, Chemical

Analysis,ChemicalProcessesandFoodEngineering.
 Microfluidics

Physical characteristics

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.

Microfluidicsasbottomuptechnique

BottomuporTopdown?

Top-down Bottom-up
Microfluidicutilizationforparticlemorphologicalcontrol

R.K.Shaha,etal.MaterialsToday,vol11,number4,April2008.
Scaleoutinmicrofluidics

Microfluidicsscalingofproductionis
obtainedbyusingthesamedevices
inparallel.

Scale-Up Scale-out
 Microfluidics

MicroprocessesNanoparticles

By combining geometry design of microchannels and fluid

flowrateispossibletoobtainparticleswithhighsizecontrol,
reproducibilityandlowpolidispersivity.
Microfluidics is a powerful tool to obtain particles in micro
andnanoscaleandforencapsulatedrugsbasedon:
Emulsions (simple & double)

Liposomes

Nanocrystals
 Emulsions
BatchVsContinuous
Microfluidic devices

MineralOil
Drop
Polymeric Outlet
Solution

MineralOil
MineralOil Droplet
Oulet

Polymeric
Solution
 Currentworksin
microfluidicsatIPT
Emulsiongeneratorsusingglassdevices

Simple emulsion production

(Water-oil) and droplet size Vs.
input flow ratio

J.N.Schianti,etal.Emulsionproductionusingglass
microfluidicdevices,Proc:IBERSENSOR2010
 Microandnanoparticleswithmicromixers

MicrographsofPLGA(Poly(DLlactideco ComparisonbetweenTurraxagitation
glycolide)) microspherescontainingBSA andmicromixerparticlesobtained
(Bovineserumalbumin)(750x) usingmicromixers.

80

60

R eleased B SA (% )
40

20

0
0 50 100 150 200 250
Time (hours)
Micromixer ED2 Micromixer BD1 Conventional mechanical agitation

M.RibeiroCosta,etal.PreparationofproteinloadedPLGA
microspheresbyanemulsion/solventevaporationprocess
employingLTCCmicromixers, PowderTechnologyVol190,
p.107111,(2009)

(DCM/BD1/Q36)
 Nanoliposomeproductionviamicrofluidics

BOTTOM - UP

Liposome

MicrofluidicHydrodynamic
Focusing

J.N.Schianti,etal.Glassflowfocusingmicrofluidicdevicefor
nanoliposomeproduction,Proc:IBERSENSOR2010
 Nanocrystallizationprocessbymicrofluidics
Crystallizationprocesstoobtain rifampicinamorphousnanoparticles

BOTTOM - UP

Nanocrystals

MicrofluidicFlowFocusing
Technologicalperspectives

Microfabricationofunitoperationdevicesforchemical
processintensification,includingsynthesisofmicroand
nanoparticlesforfeasibleproducts.

Microfabricationofdevicesadaptedtotheencapsulation
processinordertodesigncapsuleoremulsionwithsizeand
morphologycontrolledincontinuousprocess.

Introductionofnewmicrofluidictechniquesforproductionof
drugdeliverynanostructuredparticles.
TechnologyTeam
CTPP Director
Dr.MariaFilomenadeA.Rodrigues(Filomena@ipt.br)

LPP
Laboratoryhead
Dr.WagnerAldeia(waldeia@ipt.br)

Researcher(PhD) 8
Researcher(MSc.) 1
Researcher 6
Laboratorytechnicians 5

Students
PhDstudent 3
PostDoctorate 1

Thankyouforyourattention!!!