Minimization of drug side effects is a hallmark of advanced targeted therapy. Herein we describe the synthesis of polysaccharide-based nanocapsules prepared from furcellaran and chitosan via layer-by-layer deposition using electrostatic interaction. Using doxorubicin as a model drug, prepared nanocapsules showed excellent drug loading properties and release influence by pH and stability. Targeted delivery of doxorubicin was achieved by nanocapsule surface modification using homing peptide (seq SMSIARLC). The synthesized nanocapsules possess excellent compatibility to eukaryotic organisms. In the case of nonmalignant cells (PNT1A and HEK-293), toxicity tests revealed the absences of DNA fragmentation, apoptosis, necrosis, and also disruption of erythrocyte membranes. In contrast, results from treatment of malignant cell lines (MDA-MB-231 and PC3) indicate good anticancer effects of synthesized bionanomaterial. Internalization studies revealed the nanocapsule's ability to enter the malignant cell lines by endocytosis and triggering the apoptosis. The occurrence of apoptosis is mostly connected to the presence of ROS and inability of DNA damage reparation. Additionally, the obtained results strongly indicate that peptide modification increases the speed of nanocapsule internalization into malignant cell lines while simultaneously nonmalignant cell lines are untouched by nanocapsules highlighting the strong selectivity of the peptide.
- MeSH
- algináty chemie MeSH
- antigeny CD31 metabolismus MeSH
- chitosan chemie MeSH
- doxorubicin aplikace a dávkování farmakokinetika MeSH
- HEK293 buňky MeSH
- hemolýza účinky léků MeSH
- koncentrace vodíkových iontů MeSH
- lékové transportní systémy metody MeSH
- léky s prodlouženým účinkem * MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nanokapsle aplikace a dávkování chemie toxicita MeSH
- peptidy chemie metabolismus MeSH
- polyelektrolyty chemie MeSH
- rostlinné gumy chemie MeSH
- testy toxicity MeSH
- uvolňování léčiv MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
It is generally believed that antibacterial essential oils have the potential to become one of the alternatives in preventing diarrheal diseases of monogastric animals. The disadvantage is their low efficiency per oral due to easy degradation during digestion in the stomach. This study compares the efficacy of chitosan, alginate-chitosan, guar gum-chitosan, xanthan gum-chitosan and pectin-chitosan nanocapsules to the synthesis of pH-responsive biopolymeric nanocapsule for Thymus vulgaris, Rosmarinus officinalis and Syzygium aromaticum essential oils. Using spectrophotometric approach and gas chromatography, release kinetics were determined in pH 3, 5.6 and 7.4. The growth rates of S. aureus and E. coli, as well as minimal inhibition concentration of essential oils were studied. The average encapsulation efficiency was 60%, and the loading efficiency was 70%. The size of the nanocapsules ranged from 100 nm to 500 nm. Results showed that chitosan-guar gum and chitosan-pectin nanocapsules released 30% of essential oils (EOs) at pH 3 and 80% at pH 7.4 during 3 h. Similar release kinetics were confirmed for thymol, eugenol and α-pinene. Minimal inhibition concentrations of Thymus vulgaris and Syzygium aromaticum essential oils ranged from 0.025 to 0.5%. Findings of this study suggest that the suitable pH-responsive nanocapsule for release, low toxicity and antibacterial activity is based on chitosan-guar gum structure.
- MeSH
- antibakteriální látky chemie farmakologie MeSH
- erytrocyty cytologie účinky léků MeSH
- Escherichia coli účinky léků růst a vývoj MeSH
- hemolýza účinky léků MeSH
- koncentrace vodíkových iontů MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- nanokapsle aplikace a dávkování chemie MeSH
- oleje prchavé chemie farmakologie MeSH
- polymery chemie MeSH
- Staphylococcus aureus účinky léků růst a vývoj MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Multidrug resistance (MDR) is a common cause of failure in chemotherapy for malignant diseases. MDR is either acquired as a result of previous repeated exposure to cytostatic drugs (P388/MDR cells) or naturally, as some tumors are congenitally resistant to chemotherapy (CT26 cells). One of the most common mechanisms of MDR is upregulation of P-glycoprotein (P-gp) expression. Here, we used HPMA copolymer conjugates, whereby the cytostatic drug doxorubicin (Dox) or the derivative of the P-gp inhibitor reversin 121 (R121) or both were covalently bound through a degradable pH-sensitive hydrazone bond. We proved that R121, when bound to a polymeric carrier, is capable of inhibiting P-gp in P388/MDR cells and sensitizing them in relation to the cytostatic activity of Dox. Conjugate bearing both Dox and R121 was found to be far more potent in P388/MDR cells than conjugate bearing Dox alone or a mixture of conjugates bearing either Dox or R121 when cytostatic activity in vitro, cell cycle arrest, accumulation of Dox in cells and induction of apoptosis were determined. Importantly, conjugate bearing R121 is also effective in vivo as it inhibits P-gp in P388/MDR tumors after intraperitoneal administration, while both the conjugate bearing Dox and R121 induces apoptosis in P388/MDR tumors more effectively than conjugate bearing Dox alone. Only conjugate bearing Dox and R121 significantly inhibited P388/MDR tumor growth and led to the prolonged survival of treated mice. However, the most dramatic antitumor activity of this conjugate was found in the CT26 tumor model where it completely cured six out of eight experimental mice, while conjugate bearing Dox alone cured no mice.
- MeSH
- chemorezistence MeSH
- cytostatické látky aplikace a dávkování MeSH
- doxorubicin aplikace a dávkování MeSH
- experimentální nádory farmakoterapie patologie MeSH
- inbrední kmeny myší MeSH
- methakryláty chemie MeSH
- mnohočetná léková rezistence MeSH
- myši nahé MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nanokapsle aplikace a dávkování chemie MeSH
- nanokonjugáty aplikace a dávkování chemie MeSH
- oligopeptidy aplikace a dávkování MeSH
- P-glykoprotein antagonisté a inhibitory MeSH
- protokoly protinádorové kombinované chemoterapie aplikace a dávkování MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Identifying intended or accidental cellular targets for drug delivery systems is highly relevant for evaluating therapeutic and toxic effects. However, limited knowledge exists on the distribution of nano- and micrometer-sized carrier systems at the cellular level in different organs. We hypothesized that clinically relevant carrier materials, differing in composition and size, are able to target distinct myeloid cell subsets that control inflammatory processes, such as macrophages, neutrophils, monocytes and dendritic cells. Therefore, we analyzed the biodistribution and in vivo cellular uptake of intravenously injected poly(N-(2-hydroxypropyl) methacrylamide) polymers, PEGylated liposomes and poly(butyl cyanoacrylate) microbubbles in mice, using whole-body imaging (computed tomography - fluorescence-mediated tomography), intra-organ imaging (intravital multi-photon microscopy) and cellular analysis (flow cytometry of blood, liver, spleen, lung and kidney). While the three carrier materials shared accumulation in tissue macrophages in liver and spleen, they notably differed in uptake by other myeloid subsets. Kupffer cells and splenic red pulp macrophages rapidly take up microbubbles. Liposomes efficiently reach dendritic cells in liver, lung and kidney. Polymers exhibit the longest circulation half-life and target endothelial cells in the liver, neutrophils and alveolar macrophages. The identification of such previously unrecognized target cell populations might open up new avenues for more efficient drug delivery.
- MeSH
- cílená molekulární terapie metody MeSH
- liposomy chemie MeSH
- mikrobubliny terapeutické užití MeSH
- myeloidní buňky chemie cytologie MeSH
- myši nahé MeSH
- myši MeSH
- nanokapsle aplikace a dávkování chemie MeSH
- orgánová specificita MeSH
- polymery chemie MeSH
- testování materiálů MeSH
- tkáňová distribuce MeSH
- tobolky aplikace a dávkování chemie MeSH
- vnitřnosti chemie cytologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
