Liposomes are one of the most important drug delivery vectors, nowadays used in clinics. In general, polyethylene glycol (PEG) is used to ensure the stealth properties of the liposomes. Here, we have employed hydrophilic, biocompatible and highly non-fouling N-(2-hydroxypropyl) methacrylamide (HPMA)-based copolymers containing hydrophobic cholesterol anchors for the surface modification of liposomes, which were prepared by the method of lipid film hydration and extrusion through 100 nm polycarbonate filters. Efficient surface modification of liposomes was confirmed by transmission electron microscopy, atomic force microscopy, and gradient ultracentrifugation. The ability of long-term circulation in the vascular bed was demonstrated in rabbits after i.v. application of fluorescently labelled liposomes. Compared to PEGylated liposomes, HPMA-based copolymer-modified liposomes did not induce specific antibody formation and did not activate murine and human complement. Compared with PEGylated liposomes, HPMA-based copolymer-modified liposomes showed a better long-circulating effect after repeated administration. HPMA-based copolymer-modified liposomes thus represent suitable new candidates for a generation of safer and improved liposomal drug delivery platforms.

• MeSH
• akrylamidy chemie   MeSH
• aktivace komplementu účinky léků   MeSH
• cholesterol chemie   krev   MeSH
• hydrofobní a hydrofilní interakce * MeSH
• králíci MeSH
• lékové transportní systémy MeSH
• lidé MeSH
• liposomy * MeSH
• myši MeSH
• polyethylenglykoly * chemie   MeSH
• polymery chemie   MeSH
• povrchové vlastnosti * MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Nanoparticles (NPs) represent an emerging platform for diagnosis and treatment of various diseases such as cancer, where they can take advantage of enhanced permeability and retention (EPR) effect for solid tumor accumulation. To improve their colloidal stability, prolong their blood circulation time and avoid premature entrapment into reticuloendothelial system, coating with hydrophilic biocompatible polymers is often essential. Most studies, however, employ just one type of coating polymer. The main purpose of this study is to head-to-head compare biological behavior of three leading polymers commonly used as "stealth" coating materials for biocompatibilization of NPs poly(ethylene oxide), poly(2-ethyl-2-oxazoline) and poly[N-(2-hydroxypropyl)methacrylamide] in an in vivo animal solid tumor model. We used radiolabeled biodegradable hydroxyapatite NPs as a model nanoparticle core within this study and we anchored the polymers to the NPs core by hydroxybisphosphonate end groups. The general suitability of polymers for coating of NPs intended for solid tumor accumulation is that poly(2-ethyl-2-oxazoline) and poly(ethylene oxide) gave comparably similar very good results, while poly[N-(2-hydroxypropyl)methacrylamide] was significantly worse. We did not observe a strong effect of molecular weight of the coating polymers on tumor and organ accumulation, blood circulation time, biodistribution and biodegradation of the NPs.

• Publikační typ
• časopisecké články MeSH

The ability of peculiar iron oxide nanoparticles (IONPs) to evade the immune system was investigated in vivo. The nanomaterial was provided directly into the farming water of zebrafish ( Danio rerio) and the distribution of IONPs and the delivery of oxytetracycline (OTC) was studied evidencing the successful overcoming of the intestinal barrier and the specific and prolonged (28 days) organotropic delivery of OTC to the fish ovary. Noteworthy, no sign of adverse effects was observed. In fish blood, IONPs were able to specifically bind apolipoprotein A1 (Apo A1) and molecular modeling showed the structural analogy between the IONP@Apo A1 nanoconjugate and high-density lipoprotein (HDL). Thus, the preservation of the biological identity of the protein suggests a plausible explanation of the observed overcoming of the intestinal barrier, of the great biocompatibity of the nanomaterial, and of the prolonged drug delivery (benefiting of the lipoprotein transport route). The present study promises novel and unexpected stealth materials in nanomedicine.

• MeSH
• hematoencefalická bariéra MeSH
• hmotnostní spektrometrie MeSH
• kovové nanočástice chemie   MeSH
• lékové transportní systémy * MeSH
• ryby MeSH
• vazba proteinů MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• železité sloučeniny chemie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Itraconazole (ITZ) is an antifungal agent used clinically to treat mycotic infections. However, its therapeutic effects are limited by low solubility in aqueous media. Liposome-based delivery systems (LDS) have been proposed as a delivery mechanism for ITZ to alleviate this problem. Furthermore, PEGylation, the inclusion in the formulation of a protective "stealth sheath" of poly(ethylene glycol) around carrier particles, is widely used to increase circulation time in the bloodstream and hence efficacy. Together, these themes highlight the importance of mechanistic and structural understanding of ITZ incorporation into liposomes both with and without PEGylation because it can provide a potential foundation for the rational design of LDS-based systems for delivery of ITZ, using alternate protective polymers or formulations. Here we have combined atomistic simulations, cryo-TEM, Langmuir film balance, and fluorescence quenching experiments to explore how ITZ interacts with both pristine and PEGylated liposomes. We found that the drug can be incorporated into conventional and PEGylated liposomes for drug concentrations up to 15 mol % without phase separation. We observed that, in addition to its protective properties, PEGylation significantly increases the stability of liposomes that host ITZ. In a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayer without PEGylation, ITZ was found to reside inside the lipid bilayer between the glycerol and the double-bond regions of POPC, adopting a largely parallel orientation along the membrane surface. In a PEGylated liposome, ITZ partitions mainly to the PEG layer. The results provide a solid basis for further development of liposome-based delivery systems.

• MeSH
• antifungální látky chemie   MeSH
• farmaceutická chemie metody   MeSH
• fluorescence MeSH
• fosfatidylcholiny chemie   MeSH
• itrakonazol chemie   MeSH
• lékové transportní systémy metody   MeSH
• lipidové dvojvrstvy chemie   MeSH
• liposomy chemie   MeSH
• membrány chemie   MeSH
• ochranné látky chemie   MeSH
• polyethylenglykoly chemie   MeSH
• polymery chemie   MeSH
• povrchové vlastnosti MeSH
• rozpustnost MeSH
• Publikační typ
• časopisecké články MeSH

Bioavailability of baicalin (BAI), an example of traditional Chinese medicine, has been modified by loading into liposome. Several liposome systems of different composition i.e., lipid/cholesterol (L), long-circulating stealth liposome (L-PEG) and folate receptor (FR)-targeted liposome (L-FA) have been used as the drug carrier for BAI. The obtained liposomes were around 80 nm in diameter with proper zeta potentials about -25 mV and sufficient physical stability in 3 months. The entrapment efficiency and loading efficiency of BAI in the liposomes were 41.0-46.4% and 8.8-10.0%, respectively. The morphology details of BAI lipsosome systems i.e., formation of small unilamellar vesicles, have been determined by cryogenic transmission electron microscopy (cryo-TEM) and small angle X-ray scattering (SAXS). In vitro cytotoxicity of BAI liposomes against HeLa cells was evaluated by MTT assay. BAI loaded FR-targeted liposomes showed higher cytotoxicity and cellular uptake compared with non-targeted liposomes. The results suggested that L-FA-BAI could enhance anti-tumor efficiency and should be an effective FR-targeted carrier system for BAI delivery.

• MeSH
• antiflogistika nesteroidní chemie   farmakokinetika   farmakologie   MeSH
• difrakce rentgenového záření MeSH
• elektronová kryomikroskopie MeSH
• flavonoidy chemie   farmakokinetika   farmakologie   MeSH
• folátové receptory zakotvené GPI antagonisté a inhibitory   metabolismus   MeSH
• HeLa buňky MeSH
• konfokální mikroskopie MeSH
• kyselina listová analogy a deriváty   chemie   MeSH
• lidé MeSH
• liposomy chemie   ultrastruktura   MeSH
• maloúhlový rozptyl MeSH
• nádory děložního čípku metabolismus   patologie   MeSH
• polyethylenglykoly chemie   MeSH
• stabilita léku MeSH
• transmisní elektronová mikroskopie MeSH
• uvolňování léčiv MeSH
• viabilita buněk účinky léků   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Colloidal clusters of magnetic iron oxide nanocrystals (MIONs), particularly in the condensed pattern (co-CNCs), have emerged as new superstructures to improve further the performance of MIONs in applications pertaining to magnetic manipulation (drug delivery) and magnetic resonance imaging (MRI). Exploitation of the advantages they represent and their establishment in the area of nanomedicine demands a particular set of assets. The present work describes the development and evaluation of MION-based co-CNCs featuring for the first time such assets: High magnetization, as well as magnetic content and moment, high relaxivities (r2 = 400 and r2* = 905 s(-1) mMFe(-1)) and intrinsic loss power (2.3 nH m(2) kgFe(-1)) are combined with unprecedented colloidal stability and structural integrity, stealth and drug-loading properties. The reported nanoconstructs are endowed with additional important features such as cost-effective synthesis and storage, prolonged self-life and biocompatibility. It is finally showcased with in vivo multispectral optoacoustic tomography how these properties culminate in a system suitable for targeting breast cancer and for forceful in vivo manipulation with low magnetic field gradients.

• MeSH
• doxorubicin aplikace a dávkování   MeSH
• lékové transportní systémy MeSH
• magnety chemie   MeSH
• myši nahé MeSH
• myši MeSH
• nádory prsu patologie   MeSH
• nanočástice analýza   chemie   MeSH
• optoakustické techniky metody   MeSH
• počítačová rentgenová tomografie metody   MeSH
• polyethylenglykoly chemie   farmakokinetika   MeSH
• protinádorová antibiotika aplikace a dávkování   MeSH
• prsy patologie   MeSH
• železité sloučeniny chemie   farmakokinetika   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

This article is focused on reviewing the benefit and limitations of utilization of doxorubicin, which is one of the most widely used anticancer drug even though it causes severe side effects. The mechanism of action of common cytostatic drugs is described and special attention is paid to doxorubicin. Its pathway through the body is highlighted and its toxicity is emphasized. Finally, strategy of elimination of the negative effects induced by doxorubicin therapy is mentioned and the most widely approach – the use of liposomes – is summarized.

• Klíčová slova
• stealth, enkapsulace,
• MeSH
• cytostatické látky farmakokinetika   farmakologie   škodlivé účinky   MeSH
• doxorubicin * farmakokinetika   farmakologie   škodlivé účinky   MeSH
• lékové transportní systémy * metody   MeSH
• lidé MeSH
• liposomy metabolismus   MeSH
• nádory farmakoterapie   MeSH
• nemoci jater etiologie   MeSH
• nemoci srdce chemicky indukované   MeSH
• nežádoucí účinky léčiv * prevence a kontrola   MeSH
• polyethylenglykoly MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH