Photothermal Liposomal Drug Delivery Systems - Physicochemical Aspects in Particle Characterization and Drug Release from Light-Sensitive Drug Carriers

Lauri Viitala

Photothermal Liposomal Drug Delivery Systems - Physicochemical Aspects in Particle Characterization and Drug Release from Light-Sensitive Drug Carriers

Julkaisun otsikon käännös: Fototermiset liposomi-lääkkeenkuljetusjärjestelmät: partikkelien karakterisoinnin ja lääkkeenvapautuksen fysikaalinen kemia

Lauri Viitala

Tutkimustuotos: Doctoral Thesis › Collection of Articles

Abstrakti

Liposomi on fosfolipideistä koostuva rakenne, jonka sisällä on sen lipidikaksoiskerroksen suojaama vesifaasi. Hydrofiilista lääkeainetta voidaan ladata liposomiin, jonka sisällä ne kulkeutuvat kohdesoluunsa esimerkiksi endosytoosin avulla. Liposomit saavuttavat usein kohdesolunsa, mutta niiden passiivinen lääkkeenvapautus voi olla tehotonta. Lääkkeenkuljetussysteemit voidaan kuitenkin varustaa aktivointimekanismilla. Eräs vaihtoehto on lääkkeenvapautus valoa käyttäen. Valoherkistetty lääkkeenvapautus voidaan saavuttaa useilla strategioilla. Eräs kiinnostavimmista on valoa lämmöksi muuttavien materiaalien käyttö. Tässä tapauksessa fototerminen materiaali muuntaa absorboimansa valon lämmöksi. Fototermisiä materiaaleja ovat esimerkiksi monet kultananopartikkelit, joiden absorptio-maksimi voidaan säätää lähes mille tahansa relevantille valon aallonpituusalueelle nanopartikkelien kokoa ja muotoa muuttamalla. Toinen esimerkki on fluoresoiva merkkiaine indosyaanivihreä. Se absorboi lähi-infrapuna-alueella, joka on yleisesti turvallinen aallonpituusalue kudoksille (so. fysiologinen ikkuna). Fototerminen liposomi-lääkkeenkuljetussysteemi koostuu lääkkeellä ladatusta liposomista ja fototermisesta materiaalista. Käytännössä lääkeaine ei vapaudu lämpötiloissa, jotka ovat lipidin faasimuutoslämpötilan alapuolella. Kun fototerminen materiaalia lämpenee lokaalisti, lääkeaine vapautuu kalvon faasimuutoksen seurauksena. Tämä väitöskirja tarkastelee fototermisiä liposomi-lääkekuljettimia fysiko-kemiallisesta näkökulmasta ja tarjoaa joitakin uusia menetelmiä näiden systeemien karakterisointiin. Työ voidaan jakaa kolmeen osa-alueeseen. Ensimmäisessä osassa fototermisiin liposomi-formulaatioihin kohdistuvia valo-lämpö-ilmiöitä tutkittiin kvartsikidevaa'an ja fluoresenssispektroskopian avulla. Pääasiallinen havainto tutkimuksissa oli lipidikaksoiskerroksen faasimuutos ja sitä seurannut lääkkeenvapautus. Toisessa osassa tutkittiin menetelmiä liposomien havainnoimiseksi. Vakiokulman pintaplasmoniresonanssimikroskopian avulla voitiin määrittää kultananopartikkeleita sisältävien liposomien lukumäärä käyttämällä tässä työssä kehitettyä uutta analyysimenetelmää. Kolmannessa osassa liposomien pintarakennetta muokattiin lipidi-polyetyleeniglykolin (lipidi-PEG) hybridin lisäyksinä. Uusi laurdanC-merkkiaineen käyttöön perustuva tekniikka kehitettiin partikkelien muodon määrittämiseksi. Lisäksi havaittiin muutoksia lipidi-kalvon faasimuutoskäytöksessä PEG-pitoisuuden kasvaessa. Muodonmuutos ja faasimuutoskäyttäytyminen voivat tarjota joitakin hyötynäkökohtia lääkkeenvapautusta ajatellen. Yksi tällainen voisi olla lääkkeenvapautus useammassa jaksossa. Toisaalta myös polymeeri voisi toimia vapautuksen aktivoijana.

Julkaisun otsikon käännös	Fototermiset liposomi-lääkkeenkuljetusjärjestelmät: partikkelien karakterisoinnin ja lääkkeenvapautuksen fysikaalinen kemia
Alkuperäiskieli	Englanti
Pätevyys	Tohtorintutkinto
Myöntävä instituutio	Aalto-yliopisto
Valvoja/neuvonantaja	Murtomäki, Lasse, Vastuuprofessori Murtomäki, Lasse, Ohjaaja
Kustantaja	Aalto University
Painoksen ISBN	978-952-60-8435-0
Sähköinen ISBN	978-952-60-8436-7
Tila	Julkaistu - 2019
OKM-julkaisutyyppi	G5 Artikkeliväitöskirja

Tutkimusalat

valoaktivointi
fototerminen efekti
faasimuutos
lääkkeenvapautus
havaitsemismenetelmät
pintaplasmonit
PEGylointi
muodonmuutos

Pääsy asiakirjaan

http://urn.fi/URN:ISBN:978-952-60-8436-7

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Seitsonen, J. (Manager) & Rissanen, A. (Other)
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@phdthesis{aaa8002dcfda4810aee905199bcb4461,

title = "Photothermal Liposomal Drug Delivery Systems - Physicochemical Aspects in Particle Characterization and Drug Release from Light-Sensitive Drug Carriers",

abstract = "Liposome is a phospholipid structure that surrounds its aqueous cavity with a lipid bilayer. Hydrophilic drug molecules can be encapsulated in liposomes and delivered to a given target. Ideally, liposomes are internalized by the target cell via endocytosis and the hydrophilic drug is released therein. In many cases, liposomes reach their target cell but the rate of passive release remains insufficient. Luckily, this challenge can be tackled with a suitable triggering mechanism. One option is to use light. Light triggered drug release can be obtained with several strategies. One of the most interesting methods is to employ materials that convert light into heat. In this case, a photothermal agent absorbs light and releases the absorbed energy as heat. Such materials include a wide selection of gold nanoparticles that can be tuned to any relevant wavelengths by adjusting their size and shape. Another example is the fluorescent dye indocyanine green (ICG). It absorbs in the near infrared region that is safe for tissue irradiation (i.e. at the physiological window). A photothermal liposomal drug delivery system is composed of drug-encapsulated liposomes with photothermal agents. In essence, a lipid bilayer prevents drug from releasing below its phase transition temperature. However, when the photothermal agents heat up locally, the drug molecules are released as the bilayer undergoes a phase transition. This thesis addresses photothermal liposomal drug delivery systems from the physicochemical point of view and provides some new methods to characterize such systems. This work can be divided in three sections. In the first section, liposomes were coupled with photothermal agents and light-inflicted changes in the lipid bilayer were monitored with the quartz crystal microbalance and fluorescence spectroscopy. The main effect was the thermal phase transition in the lipid bilayer followed by the contents release. In the second section, methods of liposome detection were examined. Surface plasmon resonance imaging microscopy (SPRIM) was used to determine the number of encapsulated gold nanoparticles residing inside the liposomes with a new analysis method. In the third section, the prospects of surface engineering of liposomes was investigated with the addition of lipid-bound poly(ethylene glycol) (PEG). A new method, based on laurdanC, was developed to monitor the shape of the particulates. In addition, PEGylation caused changes in the phase transition behavior and shape of the lipid particulates. These features can provide new opportunities for drug delivery. These could be e.g. drug release systems with multiple release sequences and shape-shifting drug carriers with trigger polymers.",

keywords = "light triggering, photothermal effect, phase transition, drug release, detection methods, surface plasmons, PEGylation, shape transformation, valoaktivointi, fototerminen efekti, faasimuutos, l{\"a}{\"a}kkeenvapautus, havaitsemismenetelm{\"a}t, pintaplasmonit, PEGylointi, muodonmuutos, light triggering, photothermal effect, phase transition, drug release, detection methods, surface plasmons, PEGylation, shape transformation",

author = "Lauri Viitala",

year = "2019",

language = "English",

isbn = "978-952-60-8435-0",

series = "Aalto University publication series DOCTORAL DISSERTATIONS",

publisher = "Aalto University",

number = "36",

address = "Finland",

school = "Aalto University",

}

TY - BOOK

T1 - Photothermal Liposomal Drug Delivery Systems - Physicochemical Aspects in Particle Characterization and Drug Release from Light-Sensitive Drug Carriers

AU - Viitala, Lauri

PY - 2019

Y1 - 2019

N2 - Liposome is a phospholipid structure that surrounds its aqueous cavity with a lipid bilayer. Hydrophilic drug molecules can be encapsulated in liposomes and delivered to a given target. Ideally, liposomes are internalized by the target cell via endocytosis and the hydrophilic drug is released therein. In many cases, liposomes reach their target cell but the rate of passive release remains insufficient. Luckily, this challenge can be tackled with a suitable triggering mechanism. One option is to use light. Light triggered drug release can be obtained with several strategies. One of the most interesting methods is to employ materials that convert light into heat. In this case, a photothermal agent absorbs light and releases the absorbed energy as heat. Such materials include a wide selection of gold nanoparticles that can be tuned to any relevant wavelengths by adjusting their size and shape. Another example is the fluorescent dye indocyanine green (ICG). It absorbs in the near infrared region that is safe for tissue irradiation (i.e. at the physiological window). A photothermal liposomal drug delivery system is composed of drug-encapsulated liposomes with photothermal agents. In essence, a lipid bilayer prevents drug from releasing below its phase transition temperature. However, when the photothermal agents heat up locally, the drug molecules are released as the bilayer undergoes a phase transition. This thesis addresses photothermal liposomal drug delivery systems from the physicochemical point of view and provides some new methods to characterize such systems. This work can be divided in three sections. In the first section, liposomes were coupled with photothermal agents and light-inflicted changes in the lipid bilayer were monitored with the quartz crystal microbalance and fluorescence spectroscopy. The main effect was the thermal phase transition in the lipid bilayer followed by the contents release. In the second section, methods of liposome detection were examined. Surface plasmon resonance imaging microscopy (SPRIM) was used to determine the number of encapsulated gold nanoparticles residing inside the liposomes with a new analysis method. In the third section, the prospects of surface engineering of liposomes was investigated with the addition of lipid-bound poly(ethylene glycol) (PEG). A new method, based on laurdanC, was developed to monitor the shape of the particulates. In addition, PEGylation caused changes in the phase transition behavior and shape of the lipid particulates. These features can provide new opportunities for drug delivery. These could be e.g. drug release systems with multiple release sequences and shape-shifting drug carriers with trigger polymers.

AB - Liposome is a phospholipid structure that surrounds its aqueous cavity with a lipid bilayer. Hydrophilic drug molecules can be encapsulated in liposomes and delivered to a given target. Ideally, liposomes are internalized by the target cell via endocytosis and the hydrophilic drug is released therein. In many cases, liposomes reach their target cell but the rate of passive release remains insufficient. Luckily, this challenge can be tackled with a suitable triggering mechanism. One option is to use light. Light triggered drug release can be obtained with several strategies. One of the most interesting methods is to employ materials that convert light into heat. In this case, a photothermal agent absorbs light and releases the absorbed energy as heat. Such materials include a wide selection of gold nanoparticles that can be tuned to any relevant wavelengths by adjusting their size and shape. Another example is the fluorescent dye indocyanine green (ICG). It absorbs in the near infrared region that is safe for tissue irradiation (i.e. at the physiological window). A photothermal liposomal drug delivery system is composed of drug-encapsulated liposomes with photothermal agents. In essence, a lipid bilayer prevents drug from releasing below its phase transition temperature. However, when the photothermal agents heat up locally, the drug molecules are released as the bilayer undergoes a phase transition. This thesis addresses photothermal liposomal drug delivery systems from the physicochemical point of view and provides some new methods to characterize such systems. This work can be divided in three sections. In the first section, liposomes were coupled with photothermal agents and light-inflicted changes in the lipid bilayer were monitored with the quartz crystal microbalance and fluorescence spectroscopy. The main effect was the thermal phase transition in the lipid bilayer followed by the contents release. In the second section, methods of liposome detection were examined. Surface plasmon resonance imaging microscopy (SPRIM) was used to determine the number of encapsulated gold nanoparticles residing inside the liposomes with a new analysis method. In the third section, the prospects of surface engineering of liposomes was investigated with the addition of lipid-bound poly(ethylene glycol) (PEG). A new method, based on laurdanC, was developed to monitor the shape of the particulates. In addition, PEGylation caused changes in the phase transition behavior and shape of the lipid particulates. These features can provide new opportunities for drug delivery. These could be e.g. drug release systems with multiple release sequences and shape-shifting drug carriers with trigger polymers.

KW - light triggering

KW - photothermal effect

KW - phase transition

KW - drug release

KW - detection methods

KW - surface plasmons

KW - PEGylation

KW - shape transformation

KW - valoaktivointi

KW - fototerminen efekti

KW - faasimuutos

KW - lääkkeenvapautus

KW - havaitsemismenetelmät

KW - pintaplasmonit

KW - PEGylointi

KW - muodonmuutos

KW - light triggering

KW - photothermal effect

KW - phase transition

KW - drug release

KW - detection methods

KW - surface plasmons

KW - PEGylation

KW - shape transformation

M3 - Doctoral Thesis

SN - 978-952-60-8435-0

T3 - Aalto University publication series DOCTORAL DISSERTATIONS

PB - Aalto University

ER -

Photothermal Liposomal Drug Delivery Systems - Physicochemical Aspects in Particle Characterization and Drug Release from Light-Sensitive Drug Carriers

Abstrakti

Tutkimusalat

Pääsy asiakirjaan

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