4 research outputs found
PEG-PLGA polymersomes as carriers of bioactive substances
Celem tej pracy magisterskiej jest scharakteryzowanie procesu enkapsulacji i uwalniania substancji bioaktywnych (porfiryny mTHPP, leku - itrakonazolu) oraz zwi膮zk贸w modelowych (pirenu, perylenu) w no艣nikach polimerowych, jakimi s膮 polimerosomy PEG-PLGA. Przy u偶yciu cryo-TEM wykonano zdj臋cia p臋cherzyk贸w oraz okre艣lono ich rozmiar. Wykonano pomiary DLS w celu wyznaczenia promienia hydrodynamicznego syntezowanych polimerosom贸w, ich dyspersyjno艣ci i potencja艂u zeta. Metodami spektrofluorymetrycznymi przeprowadzono pomiary wnikania oraz uwalniania badanych substancji, uzyskuj膮c ich czas wnikania, sta艂膮 wnikania KB (ang. the effective binding constant) oraz sta艂膮 Sterna-Volmera KSV. Zrealizowano r贸wnie偶 pomiary izoterm 袩-A oraz wykonano zdj臋cia na mikroskopie BAM dla monowarstw powsta艂ych z kopolimeru PEG-PLGA, itrakonazolu oraz ich mieszanin w stosunku molowym. Dodatkowo przeprowadzono pomiary DSC, s艂u偶膮ce do okre艣lenia hydratacji warstwy PLGA oraz pomiary spektrometryczne UV-Vis maj膮ce na celu charakterystyk臋 spektraln膮 badanych zwi膮zk贸w.The purpose of the thesis is characteristic of encapsulation and release process of bioactive substances (mTHPP porphyrin, itraconazole) and model compounds (pyrene, perylene) in polymer carriers - PEG-PLGA polymersomes. Using the Cryo-TEM images of vesicles, size was determined. DLS measurements were made to determine the size distribution of synthesized polymerosomes, dispersion and zeta potential. Spectrophotometric methods have been used to measure the penetration and release of using substances. Obtained their penetration time, the effective binding constant (KB), and the Stern-Volmera constant (KSV). The measurements of the 袩-A isotherms were made and the BAM microscope images were made for monolayers of PEG-PLGA copolymer, itraconazole and their mixtures in a molar ratio. In addition, DSC measurements were used to determine the hydration of the PLGA layer and UV-Vis spectrometric measurements aimed at the spectral characteristics of using compounds
Modification of poly(allylamine hydrochloride) in order to obtain strong polyelectrolyte and the interactions of obtained derivatives of poly(allylamine hydrochloride) with lipid membranes.
W ramach pracy licencjackiej zmodyfikowano poli(chlorowodorek alliloaminy)(PAH) w celu uzyskania mocnego polielektrolitu oraz zmniejszenia cytotoksyczno艣ci podstawowego polimeru. Zbadano r贸wnie偶 oddzia艂ywanie pochodnych PAH'u z b艂onami lipidowymi. Interakcja polikationu z liposomami jest bardzo wa偶nym aspektem w zastosowaniach biofizycznych i medycznych. Wykorzystuje si臋 j膮 np. do tworzenia uk艂ad贸w liposom-polimer, kt贸re odgrywaj膮 istotn膮 rol臋 w nowych systemach dostarczania lek贸w (DDS). W pierwszej cz臋艣ci pracy przeprowadzono syntez臋 PAH'u ze spermin膮. Modyfikacja poli(chlorowodorku alliloaminy) przebieg艂a w tr贸j etapowej syntezie:1. Przy艂膮czenie bezwodnika bursztynowego.2. Zmetylowanie wcze艣niej uzyskanego polimeru.3. Przy艂膮czenie sperminy.Po ka偶dym etapie modyfikacji produkt zosta艂 zbadany za pomoc膮 spektroskopii w podczerwieni (IR), spektroskopii magnetycznego rezonansu j膮drowego (NMR) oraz analizy elementarnej (CHN).W drugiej cz臋艣ci pracy zbadano oddzia艂ywanie dw贸ch pochodnych poli(chlorowodorku alliloaminy)(jednego, zmodyfikowanego w 21% kwasem stearynowym i drugiego, dodekanalem w 33%). Pocz膮tkowo, za pomoc膮 DLS okre艣lono optymalne warunki, w kt贸rych uk艂ady liposom-polimer s膮 stabilne. Nast臋pnie wykonano badania spektrofluorymetryczne procesu uwalniania kalceiny (modelowego leku) z liposom贸w. Wybrano kalcein臋 do tych bada艅 ze wzgl臋du na jej 艣wietne w艂a艣ciwo艣ci fluorescencyjne. Dla dw贸ch pochodnych PAH鈥檜 obserwowano zmiany fluorescencji po dodaniu do roztworu z liposomami z kalcein膮 polimeru, kolejno surowicy, a na koniec detergentu.The main objective of the thesis was modification of poly(allylamine hydrochloride) in order to obtain strong polyelectrolyte and mitigation cytotoxicity of basic polymer. Also the interactions of obtained derivatives of PAH with lipid membranes were examined. Polycation interaction with liposomes is a very important aspect in biophysical and medical applications. It is used for example to create systems liosome-polymer, which play an important role in the new Drug Delivery Systems (DDS).In the first part of thesis the synthesis PAH with spermine was run. Modification of poly(allylamine hydrochloride) went in three-step synthesis:1. Incorporation of succinic acid anhydride into PAH.2. Methylation previously received product.3. Incorporation of spermine.After every step the product was investigated using a infrared spectroscopy (IR), nuclear magnetic resonance (NMR) and elemental analysis (CHN).In second step of thesis the interactions with lipid membranes of two derivatives of poly(allylamine hydrochloride) were examined (one, in 21% stearic acid modified and second, in 33% dodecane modified). Firstly, optimal conditions, where the systems liposome-polymer are stabile was determined using DLS. Next a calcein (drug model)release from liposomes process was examined using fluorometric analysis. For two derivatives of PAH changes in fluorescence after the addition of polymer, next serum and finally detergent to solution of liposomes with calcein was observed
Molecular Insight into Drug-Loading Capacity of PEG鈥揚LGA Nanoparticles for Itraconazole
Nanoparticles
made of amphiphilic block copolymers comprising biodegradable
core-forming blocks are very attractive for the preparation of drug-delivery
systems with sustained release. Their therapeutic applications are,
however, hindered by low values of the drug-loading content (DLC).
The compatibility between the drug and the core-forming block of the
copolymer is considered the most important factor affecting the DLC
value. However, the molecular picture of the hydrophobic drug鈥揷opolymer
interaction is still not fully recognized. Herein, we examined this
complex issue using a range of experimental techniques in combination
with atomistic molecular dynamics simulations. We performed an analysis
of the interaction between itraconazole, a model hydrophobic drug,
and a poly颅(ethylene glycol)鈥損oly颅(lactide-<i>co</i>-glycolide) (PEG鈥揚LGA) copolymer, a biodegradable copolymer
commonly used for the preparation of drug-delivery systems. Our results
clearly show that the limited capacity of the PEG鈥揚LGA nanoparticles
for the accumulation of hydrophobic drugs is due to the fact that
the drug molecules are located only at the water鈥損olymer interface,
whereas the interior of the PLGA core remains empty. These findings
can be useful in the rational design and development of amphiphilic
copolymer-based drug-delivery systems