Imiquimod (IMQ) is an immunostimulating agent used in the treatment of basal cell carcinoma and actinic keratosis. Due to its low solubility and poor skin bioavailability, the dermal formulation of IMQ remains challenging. In analogy to tyre compounds used in Formula 1 racing, we compare four types of nanosystems belonging to three groups: (i) "hard" nanoparticles in the form of IMQ nanocrystals, (ii) "intermediate" nanoparticles in the form of liposomes and lipid nanocapsules, and (iii) "soft" nanoparticles in the form of a nanoemulsion based on oleic acid. The nanoemulsion and nanocrystals were able to incorporate the highest amount of IMQ (at least 2 wt%) compared to liposomes (0.03 wt%) and lipid nanocapsules (0.08 wt%). Regarding size, liposomes, and lipid nanocapsules were rather small (around 40 nm) whereas nanocrystals and nanoemulsion were larger (around 200 nm). All developed nanoformulations showed high efficiency to deliver IMQ into the skin tissue without undesirable subsequent permeation through the skin to acceptor. Especially, the 2 wt% IMQ nanoemulsion accumulated 129 μg/g IMQ in the skin, compared to 34 μg/g of a 5 wt% commercial cream. The effects of the respective nanoparticulate systems were discussed with respect to their possible diffusion kinetics (Brownian motion vs. settling) in the aqueous phase.
- MeSH
- imichimod chemie MeSH
- kůže metabolismus MeSH
- lipidy farmakologie MeSH
- liposomy * farmakologie MeSH
- nanokapsle * MeSH
- Publikační typ
- časopisecké články MeSH
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
Nanoencapsulation is a promising approach to enhance the therapeutic potential of a drug. Herein, three selected naphthoquinone (NTQ) derivatives, based on the IC50 value against Trypanosoma evansi, were encapsulated using gum damar as biocompatible and biodegradable natural gum via nanoprecipitation method. Nanoformulation of NTQs (NNTQs) was less than 150 nm in size, was found to be stable and released the drug in a sustained manner. All the three NNTQs exhibited significant antitrypanosomal effect and morphological changes at approximately two to three times lesser drug concentrations. The nanoformulations exhibited enhanced production of reactive oxygen species (ROS) in the axenic culture of T. evansi and less cytotoxic effect on horse peripheral blood mononuclear cells relative to pure NTQs. As evidenced by flow cytometry, the NNTQs showed dose-dependent and time-dependent increased transition of live cells (AV-PI-) to early apoptotic cells (AV+PI-), late apoptotic cells (AV-PI+), and necrotic cells (AV+PI+) using annexin V/propidium iodide probe analysis. The results concluded that NNTQs induced more ROS, apoptosis and necrotic effects that exhibited more inhibitory effect on the growth of T. evansi with respect to respective NTQ by themselves.
- MeSH
- koně MeSH
- leukocyty mononukleární MeSH
- naftochinony * farmakologie MeSH
- nanokapsle * MeSH
- reaktivní formy kyslíku MeSH
- Trypanosoma * MeSH
- zvířata MeSH
- Check Tag
- zvířata 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
This study investigated the effect of the topical treatment with meloxicam-loaded nanocapsules (M-NC) on symptoms, inflammatory response and oxidative parameters in an atopic dermatitis (AD) model in BALB/c mice. 2,4-Dinitrochlorobenzene (DNCB) was applied to the dorsal skin on days 1–3 for sensitization. Mice were challenged with DNCB on the ear (on days 14–29) and dorsal skin (on days 14, 17, 20, 23, 26, and 29). Treatments with blank nanocapsules (B-NC), free meloxicam (M-F) or M-NC were applied to the backs of the mice from days 14 to 29. On the day 30, skin severity scores and scratching behaviour were determined. After that, ears and dorsal skin were removed for determination of inflammatory parameters (edema and myeloperoxidase (MPO) activity) and oxidative parameters (thiobarbituric acid reactive species (TBARS) and non-protein thiol (NPSH) levels), respectively. DNCB increased the severity of skin lesions, scratching behaviour, edema and MPO activity of ears and dorsal skin TBARS levels. M-NC reversed skin severity scores, scratching behaviour and inflammatory response induced by DNCB. B-NC and M-F did not have effect in this model. In summary, meloxicam carried by polymeric nanocapsules reversed inflammatory response and ameliorated symptoms in an AD model.
- MeSH
- aplikace kožní MeSH
- atopická dermatitida * farmakoterapie MeSH
- lékové formy MeSH
- meloxikam aplikace a dávkování MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední BALB C MeSH
- nanokapsle MeSH
- nosiče léků MeSH
- výsledek terapie MeSH
- způsoby aplikace léků MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem 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
