The transdermal application of actives offers numerous advantages over other conventional routes. Namely, a stable level of drugs in the bloodstream and reduced side effects are the argument for topical administration. Unfortunately, the exceptional skin barrier and unsuitable physico-chemical properties of drugs are the limiting factors for the transdermal passage. It is possible to overcome this by incorporating the drug into nano-carriers to enhance its permeation through the skin barrier. For this purpose, we prepared lipid nanocapsules (LNCs) to modulate skin passage of three pharmaceutically important drugs - indomethacin (IND), diclofenac sodium (DF) and caffeine (CF). We present a stable system prepared by the phase inversion temperature method with particle size under 100 nm and PDI < 0.1 with great encapsulation efficiency for indomethacin and diclofenac. By FTIR it was possible to confirm (for IND and DF) or disprove (in case of CF) the incorporation of a drug into the LNCs. By ex vivo permeation experiments on porcine skin, we confirmed the superior effect of the LNCs on the APIs skin passage. The drug permeated through the skin with higher intensity when delivered from LNCs compared to other standard formulations. We show that lipid nanocapsules play an important role in enhanced topical application of actives.
- MeSH
- aplikace kožní MeSH
- diklofenak MeSH
- indomethacin MeSH
- lipidy chemie MeSH
- nanokapsle * chemie MeSH
- nosiče léků chemie MeSH
- velikost částic MeSH
- Publikační typ
- časopisecké články MeSH
Pickering emulsions have been known to be promising candidates for encapsulating and delivering a wide range of bioactive compounds with antioxidant potentials. In this work, we formulated and characterized zein (ZN)/chitosan (CS) stabilized Pickering emulsion. The prepared emulsions were firstly characterized by droplet size after preparation and after storage for one month at room temperature as well as after the addition of prebiotic gum Arabic (GA). Rheological measurements were further carried out to see the behavior and stability of these emulsions after storage. Thereafter, vit-D3 was encapsulated, and the antioxidant activity of the emulsions system were evaluated. The results showed that no significant change in the mean droplet diameter of the emulsions was observed after storage for a month. This claim was further confirmed by their rheological measurements particularly, the emulsions prepared with ZN/CS ratio of 1:2 having 50% oil contents exhibited significant stability. GA addition caused a gradual increase in the droplet size up to some level, after which it led to complete destabilization of the emulsion. Finally, to protect and deliver, vit-D3 was successfully loaded in these emulsions. No significant difference in the DPPH radical scavenging activity of the vit-D3 encapsulated emulsions was observed, showing their capability as delivery vehicles irrespective of their composition.
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
- 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
- systémy cílené aplikace léků metody 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
Current scenario of bio-nanotechnology, successfully fabrication of ultrafine titanium dioxide nanoparticles (TiO2NPs) using various biological protein sources for the multipurpose targets. The present research report involves synthesis of TiO2NPs using antimicrobial peptide (AMP) crustin (Cr). Crustin previously purified from the blue crab, Portunus pelagicus haemolymph, by blue Sepharose CL-6B matrix assisted affinity column chromatography. Synthesized Cr-TiO2NPs was physico-chemically characterized by UV-Visible spectroscopy (UV-Visible), X-ray Diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), High-resolution transmission electron microscopy (HR-TEM) and zeta potential examination. X-ray diffraction analysis for crystalline nature and phase identification of titanium dioxide nanoparticles was absorbed. Functional groups were found through FTIR ranges between 1620 and 1700 cm-1. HR-TEM analysis showed that the synthesized Cr-TiO2NPs tetragonal shape and sizes ranging from 10 to 50 nm. Finally, the surface charge of the Cr-TiO2NPs was confirmed through zeta potential analysis. Furthermore, the characterized Cr-TiO2NPs exhibited good biofilm inhibition against GPB - S. mutans (Gram Positive Bacteria- Streptococcus mutans), GNB - P. vulgaris (Gram Negative Bacteria- Proteus vulgaris) and fungal Candida albicans. Moreover, photocatalysis demonstrated that the Cr-TiO2NPs was effectively explored the degradation of dyes. The results suggest that Cr-TiO2NPs is an excellent bactericidal, fungicidal and photocatalytic agent that can be supportively used for biomedical and industrial applications.
- MeSH
- antiinfekční látky chemie farmakologie MeSH
- biofilmy MeSH
- Candida albicans účinky léků MeSH
- Culicidae MeSH
- fotochemické procesy * MeSH
- insekticidy chemie farmakologie MeSH
- katalýza MeSH
- kationické antimikrobiální peptidy chemie farmakologie MeSH
- krabi chemie MeSH
- larva účinky léků MeSH
- lidé MeSH
- molekulární struktura MeSH
- nanokapsle chemie MeSH
- Proteus vulgaris účinky léků MeSH
- Streptococcus mutans účinky léků MeSH
- světlo MeSH
- titan chemie MeSH
- uvolňování léčiv MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
In this study, we report the in vivo anti-lymphoma efficacy and diagnostic potential of newly designed near-infrared fluorescent dye containing polymer-doxorubicin conjugates using murine models of malignant lymphomas including one cell line-derived xenograft (RAJI) and two patient-derived lymphoma xenografts (VFN-D1 and VFN-M2). Two types of passively targeted conjugates differing in architecture of the polymer backbone were synthesized. One of the conjugates was designed using a single linear polymer chain, and the second was more sophisticated with a star-shaped high-molecular-weight (HMW) polymer employing a dendrimer core. The linear HPMA copolymers were linked to the dendrimer core via a one-point attachment, thus forming a hydrophilic polymer shell. Both polymer-doxorubicin conjugates were long-circulating with reduced side effects. Both polymer prodrugs were designed as stimuli-sensitive systems in which the anti-cancer drug doxorubicin was attached to the hydrophilic copolymers via a pH-labile hydrazone linkage. Such polymer prodrugs were fairly stable in aqueous solutions at pH 7.4, and the drug was readily released in mildly acid environments at pH 5-6.5 by hydrolysis of the hydrazone bonds. In addition, polymers were labelled with near-infrared fluorescent dye enabling long term in vivo visualization. Malignant lymphomas represent the most common type of haematological malignancies. Therapy for the majority of malignant lymphomas consists of multi-agent chemotherapy based on an anthracycline doxorubicin, the most prominent side effect of which is cardiotoxicity. We have demonstrated significant anti-lymphoma efficacy of the polymer-doxorubicin conjugates when compared to equally toxic doses of conventional (unbound) doxorubicin in all tested models. Favourable pharmacokinetics for carried drug and labelled polymer carrier was observed, showing predominant uptake of the drug and polymer itself in the tumour mass. In addition, we have observed a promising diagnostic potential of fluorescently labelled polymer prodrugs. Dynamically analyzed fluorescence intensity over subcutaneously xenografted lymphomas closely corresponded to changes in the lymphoma tumour volumes, thereby enabling a non-invasive assessment of treatment efficacy.
- MeSH
- akrylamidy chemie MeSH
- antitumorózní látky chemie terapeutické užití MeSH
- dendrimery chemie MeSH
- doxorubicin chemie terapeutické užití MeSH
- fluorescenční barviva chemie MeSH
- heterografty MeSH
- hydrazony chemie MeSH
- hydrofobní a hydrofilní interakce MeSH
- koncentrace vodíkových iontů MeSH
- lidé MeSH
- lymfom diagnostické zobrazování farmakoterapie patologie MeSH
- methakryláty chemie MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nanokapsle chemie MeSH
- polymerizace MeSH
- polymery chemie MeSH
- uvolňování léčiv MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem 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 antitumorózní 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
The aim of this study was to follow the skin penetration of a model lipophilic compound (Nile red) delivered by nanoparticulate carriers, the so-called lipid nanocapsules. The nanocapsules consisting of an oil core stabilized by amixture of surfactants were prepared by the phase inversion temperature method. Varying the particle composition (the oil/surfactant ratio) nanoparticles of different size were prepared and characterized. The penetration profile of Nile red delivered into the porcine skin by the nanoparticles compared to non-particulate samples was determined using fluorescence microscopy combined with a novel, statistically robust quantitative image analysis method. This study demonstrated that lipid nanoparticles promoted the skin penetration of encapsulated Nile red in comparison with all the non-particulate samples. Nile red delivered by the lipid-based nanoparticles was able to diffuse across the stratum corneum and partition itself uniformly in the epidermis. No relationship between Nile red penetration into the skin and the particle size was found. Moreover, the presence of sodium chloride in the water phase had a negative impact on the Nile red penetration into the skin. The results indicate that the physico-chemical circumstances of the nanoparticulate formulation play the major role in the penetration of lipophilic substances into the skin.
- MeSH
- epidermis účinky léků MeSH
- fluorescenční mikroskopie MeSH
- konfokální mikroskopie MeSH
- kožní absorpce MeSH
- kůže účinky léků patologie MeSH
- lipidy chemie MeSH
- nanočástice chemie MeSH
- nanokapsle chemie MeSH
- nosiče léků chemie MeSH
- oleje chemie MeSH
- oxaziny chemie MeSH
- počítačové zpracování obrazu MeSH
- povrchově aktivní látky chemie MeSH
- prasata MeSH
- software MeSH
- systémy cílené aplikace léků MeSH
- transmisní elektronová mikroskopie MeSH
- velikost částic MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Herein, we describe an ultrasensitive specific biosensing system for detection of sarcosine as a potential biomarker of prostate carcinoma based on Förster resonance energy transfer (FRET). The FRET biosensor employs anti-sarcosine antibodies immobilized on paramagnetic nanoparticles surface for specific antigen binding. Successful binding of sarcosine leads to assembly of a sandwich construct composed of anti-sarcosine antibodies keeping the Förster distance (Ro) of FRET pair in required proximity. The detection is based on spectral overlap between gold-functionalized green fluorescent protein and antibodies@quantum dots bioconjugate (λex 400 nm). The saturation curve of sarcosine based on FRET efficiency (F₆₀₄/F₅₁₀ ratio) was tested within linear dynamic range from 5 to 50 nM with detection limit down to 50 pM. Assembled biosensor was then successfully employed for sarcosine quantification in prostatic cell lines (PC3, 22Rv1, PNT1A), and urinary samples of prostate adenocarcinoma patients.
- MeSH
- dextrany chemie ultrastruktura MeSH
- lidé MeSH
- magnetické nanočástice chemie ultrastruktura MeSH
- molekulární zobrazování metody MeSH
- monoklonální protilátky chemie imunologie MeSH
- nádorové biomarkery analýza MeSH
- nádorové buněčné linie MeSH
- nádory prostaty chemie diagnóza imunologie MeSH
- nanokapsle chemie ultrastruktura MeSH
- reprodukovatelnost výsledků MeSH
- rezonanční přenos fluorescenční energie metody MeSH
- sarkosin analýza imunologie MeSH
- senzitivita a specificita MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
