Yazarlar araştırma mümkün yapmak için Suudi Arabistan tarafından finanse edilen burs (I821) kabul. Yazarlar Cranfield Üniversitesi&#39;nde TEM analiz uzman desteği Dr Xianwei Liu müteşekkiriz.

Yağ-içinde-su emülsiyonu hazırlanması 1. <ol><li> gliseril palmitostearat (120 mg) ve izopropil miristat (60 mg), D-α-tokoferil polietilen glikol sukkinat (30 mg) ve soya fasulyesi lesitini (30 mg) tartılır ve organik çözücüler 12.5 ml (6.25 mi aseton ve 6.25 ekleyin mi etanol). Hızlı bir şekilde bir su banyosunda (katı lipid erime noktasının 5 ° C) sıcaklığı 70 ° C&#39;de karışım çözülür. </li><li> Yukarıdaki ile aynı sıcaklıkta ısıtmaya tabi Poloksamer 188 çözeltisi 1-3% (sırasıyla) elde etmek için GKD 2 O 12.5 ml Poloxamer188 125, 250 veya 375 mg ya da ekleyin. </li><li> 400 rpm&#39;de bir manyetik karıştırma altında emülsiyonlar oluşturmak için adım 1.1 damla damla yağ faz çözeltisi adım 1.2 sulu faz çözeltisi ekleyin. başka bir 4 saat organik çözücü buharlaşmasını sağlamak için 400 rpm&#39;de emülsiyonu karıştırılır. </li></ol> 2. katılaşma ve Homojenizasyon <ol><li> t bırakın2 saat / kristalleşirler katılaşması için bir soğuk odada (4 ° C) o emülsiyonu. </li><li> NLC elde edilmesi için, 10-40 dakika boyunca 10,000-15,000 rpm&#39;de bir homojenizör ile Emülsiyon dispersiyon (HSD) emülsiyonun maruz. </li></ol> NLC Hazırlama 3. Optimizasyonu <ol><li> 10.000, 15.000 ve 20.000 rpm hızda 1, 2 ve 3,% geçiren HSD bir yüzey aktif madde konsantrasyonunun ile adım 2.2 örnek al, ve sırasıyla 10, 20, 30 ve 40 dakikalık zaman aralıklarında, sırasıyla </li><li> Partikül boyutu (PS), poli dağılım indeksi (PDI), morfoloji ve ultrastrüktürü 20 örnekleri inceleyin. Not: Optimal olarak belirlenmiştir küçük boyut (155 nm) ve PDI (0.2) değerine sahip partiküller üretmek parametreler. </li></ol> DAC yüklü NLC 4. Hazırlama (NLC-Dac) <ol><li> su banyosu içinde 70 ° C&#39;de karışım erimeden önce DAC (70 mg) ilave adım 1.1 de tarif edildiği gibi yağ fazı çözeltisi hazırlayın. </li><li> P% 1 yüzey aktif madde ile adım 1.2 &#39;de tarif edildiği gibi, sulu bir faz çözelti onarılması ve 400 rpm&#39;de bir manyetik karıştırma ile bir emülsiyon oluşturmak için adım 4.1 damla damla Hazırlanan bu çözelti ilave edin. Organik çözücüler buharlaştırılmış ve daha 4 saat emülsiyonu karıştırılır. </li><li> / Katılaşmasına Aşama 2&#39;de tarif edildiği gibi kristalize ve son olarak, aşama 3&#39;te belirlenen optimum parametreler kullanılarak Emülsiyon dispersiyon (HSD) emülsiyonun tabi 2 saat boyunca soğuk bir odada (4 ° C) emülsiyon bırakın. </li></ol>

<ol><li>Loo, T. L., Housholder, G. E., Gerulath, A. H., Saunders, P. H., Farquhar, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Mechanism+of+action+and+pharmacology+studies+with+DTIC+%28NSC+45388%29%5BTitle%5D)+AND+%22Cancer+Treat+Rep%22%5BJournal%5D)">Mechanism of action and pharmacology studies with DTIC (NSC 45388).</a> Cancer Treat Rep. 60 (2), 149-152 (1976).</li>
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</ol>

Yazarlar ifşa hiçbir şey yok.

Lipid nano boyutta parçacıklar hidrofobik ilaçlar verilmesi için, son derece lipofilik bir taşıyıcı sağlamak amacıyla kullanılmıştır. Bir NLC odası ve vücut sıcaklığında katı olan katı lipid nano yapılı taşıyıcının ikinci nesil. Bir daha mükemmel kristalleşme bir NLC sonuçlarında bir sıvı lipid içine katı lipid eklenmesi, böylece ilaç yükleme verimliliğini artırmak ve aynı zamanda saklama sırasında kapsüllü ilaç sürülmesi azaltır. NLC sentez...

Dakarbazin (DAC) hücre döngüsü tutuklama ve hücre ölümüne 1 giden, nükleik asitler metilasyon veya doğrudan DNA hasarı ile anti-tümör aktivite sergiler bir alkilleştirme ajanı olan. Bir birinci kemoterapötik ajanlar olarak, DAC tek başına veya çeşitli kanserler 2-6 tedavi edilmesi için diğer kemoterapi ilaçları ile bir arada kullanılmaktadır. Bu, şimdiye kadar deri kanseri 3,7,8 en agresif formudur kutan ve metastatik melanom, tedavisinde kullanılan en aktif maddedir. yanıt oranı ise en iyi sadece% 20 olduğunu ve tedavi edici etkileri genellikle ciddi sistemik yan etkilere eşlik ediyor. Doğal haliyle, DAC hidrofiliktir ve nedeniyle ışığa 9 kararsızdır. Klinik kullanım için müsait bir formül halen intravenöz infüzyon 7,8 süspansiyon kullanılmak üzere steril bir tozdur. düşük tepki hızı ve yüksek sistemik toksisite rİlacın yedik, onun zayıf suda çözünürlüğü büyük ölçüde kaynaklanmaktadır ilaç 10 maksimum dozu sınırlayan hedef olmayan sitelerde hedef mahallinde, bu nedenle düşük kullanılabilirlik ve yüksek dağıtım. Ilaç direnci gelişimi ile birlikte intravenöz kabulden sonra hızlı bozulma ve metabolizma klinik uygulama ve ilaç 11 terapötik etkisini sınırlamak. Bu nedenle, kötü huylu melanom tedavisine yönelik alternatif bir DAC formülasyonlan geliştirmeye acil bir ihtiyaç vardır. Ve diğ., Potansiyel ilaç taşıyıcıları olarak 12 Nano yapılı parçacıkların son on yıl içinde artan ilgi çekmektedir nedeniyle ilaç yüklemesine geliştirmek için kabiliyetleri Marilene tarafından gözden lipozomlar ihtiva eden koloidal sistemler, miseller ya da nano yapılı parçacıklar yoğun bir ilaç verme kullanımları için incelenmiştir verimlilik, kontrol ilacı bırakma, ilaçların farmakokinetik ve biodistribution ve bu nedenle r geliştirmekbunun sonucunda ilaç sistemik toksisite 13 educe. Sadece birkaç nanoformulations Ancak verilmedi dejenerasyonu ilacın, yüksek ilaç çözünürlüğünün korunması gösteren kadar DAC teslimat için incelenmiş, ve terapötik etki 10,14,15 iyileştirilmiştir. Ancak bazıları da maliyet etkin olmayan sentetik polimer nanopartiküller kullanırken düşük kapsülleme verimliliği muzdarip bu formülasyonlar. Katı ve sıvı lipidlerin bir karışımından yapılmış Nano yapısındaki yağ taşıyıcılar (NLC), ilaç verme 16,17 geliştirilmiştir. Kapsüllenecek ilaçlar yüksek yükleme elde ve serbest 19 kontrollü, genellikle, sıvı lipid ve bir katı lipid fazlar 18 hem de çözünebilir. Bu çalışma, gliseril palmitostearat ve lipidler gibi izopropil miristat ile NLC-kapsülleme dayalı yeni bir DAC formülasyon geliştirmektir. Preparasyon katılan yağ içinde-su emülsiyonu, buharlaştırma, katılaşma ve homogenization. Preparasyonlar olarak kendisine boyut, şekil, İnce ve dispersiteleri ilaç kapsülleme verimliliği ve ilaç yüklemesi 20 karakterize edilmiştir.

<table><tbody><tr><td>Dacarbazine (DAC)</td><td>Sigma Aldrich (Gillingham Dorset, UK)</td><td>D2390-100MG</td><td>drug used for uploading</td></tr><tr><td>glyceryl palmitostearate&amp;nbsp;</td><td>Gattefoss&amp;eacute; (Saint_Priest_c&amp;eacute;dex, France)</td><td>85251-77-0</td><td>solid lipid&amp;nbsp;</td></tr><tr><td>d-&amp;alpha;- Tocopherol polyethylene glycol succinate (TPGS)</td><td>Sigma Aldrich (Gillingham Dorset, UK)</td><td>57668</td><td>lipid phase surfactant</td></tr><tr><td>Poloxamer 188</td><td>Sigma Aldrich (Gillingham Dorset, UK)</td><td>15759-1KG</td><td>liqiud phase surfactant</td></tr><tr><td>Acetone&amp;nbsp;</td><td>Sigma Aldrich (Gillingham Dorset, UK)</td><td>650501-1L</td><td>organic solvent</td></tr><tr><td>Ethanol&amp;nbsp;</td><td>Sigma Aldrich (Gillingham Dorset, UK)</td><td>459836-1L</td><td>organic solvent</td></tr><tr><td>Soybean lecithin (SL)</td><td>Cuisine Innovation (Dijon, France)</td><td>SLL1402</td><td>lipid phase surfactant</td></tr><tr><td>Double-distilled water was collected in our laboratory from</td><td>Millipore-Q Gradient A10 ultra-pure water system (Millipore, France)</td><td>SAS - 67120&amp;nbsp;</td><td>aqueous phase&amp;nbsp;</td></tr><tr><td>T 25 digital ULTRA-TURRAX</td><td>IKA</td><td>3725000</td><td>as high shear disperser</td></tr><tr><td>Hotplate Magnetic Stirrer</td><td>Scientific Support, Inc</td><td>1454&amp;nbsp;</td><td>emulsion homogenization</td></tr></tbody></table>

encapsulation of cancer therapeutic agent dacarbazine using nanostructured lipid carrier

Klinik kullanımda dakarbazin (DAC) tek bir formül nedeniyle sulu çözelti içinde ilacın düşük dağılma için zayıf bir terapötik profil gösteren damar içi infüzyon vardır. Bunun üstesinden gelmek için, gliseril palmitostereat ve izopropil miristat oluşan bir nano yapılı lipit taşıyıcının (NLC) SAD kapsüllemek için geliştirilmiştir. kontrollü bir ebada sahip nlcs yağ-su emülsiyonu katılaşması aşağıdaki yüksek kesme dispersiyon (HSD) kullanılarak elde edildi. yüzey aktif madde konsantrasyonu, hız ve HSD süresi de dahil olmak üzere sentez parametreleri sırasıyla mV, boyut, çoklu-dağıtılabilirlik indeksini ve 155 ± 10 nm zeta potansiyeli ile en az NLC elde etmek için 0.2 ± 0.01, ve -43,4 ± 2 optimize edilmiştir. uygun parametreler, DAC-yüklü NLC hazırlanması için kullanılmıştır. DAC ile yüklenen bileşke NLC sırasıyla, boyut, çoklu-dağıtılabilirlik indeksi ve 190 ± 10 nm zeta potansiyeli, 0.2 ± 0.01 ve -43,5 ± 1.2 mV sahipti. İlaç kapsülleme efrasyonlarımız ve ilaç yükleme sırasıyla% 98 ve% 14 olmuştur. Bu NLC DAC terapötik profilini geliştirmek için ilaç taşıyıcı olarak yeni bir potansiyel aday olabileceğini ima NLC kullanarak DAC kapsüllenmesi ilk rapor vardır.

Farklı parametrelerle gliserilpalmitostearat ve izopropil miristat kullanarak NLC ve NLC-DAC hazırlıkları PS, PDI, morfoloji ve ultrastrüktürü 20 karakterize edildi. Nlcs PS ve PDI yüzey konsantrasyonu, HSD hız ve süresi bağımlı idi. PS ve nlcs KAE ile değerlendirildiği gibi, en iyi sonuçlar 1 yüzey aktif madde ve% nedenle wwew NLC için en iyi parametreleri olarak seçilmiştir, 30 dakika (Şekil 1A, B ve C) ...

Watch this Scientific Journal Video about Encapsulation of Cancer Therapeutic Agent Dacarbazine Using Nanostructured Lipid Carrier at JoVE.com

Encapsulation of Cancer Therapeutic Agent Dacarbazine Using Nanostructured Lipid Carrier

nano yapılı lipit taşıyıcının (NLC) sentezi için en yaygın olarak kullanılan yöntem, yağ-su emülsiyonu, homojenizasyon ve katılaşma içerir. Bu dakarbazin teslimat için potansiyel bir taşıyıcı madde gibi arzu edilen boyutu, geliştirilmiş ilaç enkapsülasyonu ve ilaç yükleme verimliliği ile NLC elde etmek katılaştırmadan sonra yüksek kesme dispersiyon uygulayarak buradan değiştirildi.

Nano yapılı lipid taşıyıcı kullanılarak kanser terapötik dakarbazin kapsüllenmesi

The only formula of dacarbazine (Dac) in clinical use is intravenous infusion, presenting a poor therapeutic profile due to the low dispersity of the drug ...

encapsulation-cancer-therapeutic-agent-dacarbazine-using

Research

JoVE Journal

Chemistry

11.1K Görüntüleme.  Cranfield University.  nano yapılı lipit taşıyıcının (NLC) sentezi için en yaygın olarak kullanılan yöntem, yağ-su emülsiyonu, homojenizasyon ve katılaşma içerir. Bu dakarbazin teslimat için potansiyel bir taşıyıcı madde gibi arzu edilen boyutu, geliştirilmiş ilaç enkapsülasyonu ve ilaç yükleme verimliliği ile NLC elde etmek katılaştırmadan sonra yüksek kesme dispersiyon uygulayarak buradan değiştirildi. 

Video: Encapsulation of Cancer Therapeutic Agent Dacarbazine Using Nanostructured Lipid Carrier

Anticancer Efficacy of Photodynamic Therapy with Lung Cancer-Targeted Nanoparticles

Photodynamic therapy (PDT) is a non-invasive and non-surgical method representing an attractive alternative choice for lung cancer treatment. Photosensitizers selectively accumulate in tumor tissue and lead to tumor cell death in the presence of oxygen and the proper wavelength of light.
To increase the therapeutic effect of PDT, we developed both photosensitizer- and anticancer agent-loaded lung cancer-targeted nanoparticles. Both enhanced permeability and retention (EPR) effect-based passive targeting and hyaluronic-acid-CD44 interaction-based active targeting were applied. CD44 is a well-known hyaluronic acid receptor that is often introduced as a biomarker of non-small cell lung cancer. 
In addition, a combination of PDT and chemotherapy is adopted in the present study. This combination concept may increase anticancer therapeutic effects and reduce adverse reactions. 
We chose hypocrellin B (HB) as a novel photosensitizer in this study. It has been reported that HB causes higher anticancer efficacy of PDT compared to hematoporphyrin derivatives1. Paclitaxel was selected as the anticancer drug since it has proven to be a potential treatment for lung cancer2. 
The antitumor efficacies of photosensitizer (HB) solution, photosensitizer encapsulated hyaluronic acid-ceramide nanoparticles (HB-NPs), and both photosensitizer- and anticancer agent (paclitaxel)-encapsulated hyaluronic acid-ceramide nanoparticles (HB-P-NPs) after PDT were compared both in vitro and in vivo. The in vitro phototoxicity in A549 (human lung adenocarcinoma) cells and the in vivo antitumor efficacy in A549 tumor-bearing mice were evaluated.
The HB-P-NP treatment group showed the most effective anticancer effect after PDT. In conclusion, the HB-P-NPs prepared in the present study represent a potential and novel photosensitizer delivery system in treating lung cancer with PDT.

Photodynamic therapy (PDT) is an alternative choice for lung cancer treatment. To increase the therapeutic effect of PDT, lung cancer-targeted nanoparticles combined with chemotherapy were developed. Both in vitro and in vivo anticancer efficacies of PDT with prepared nanoparticles were evaluated.

Akciğer Kanseri Hedefli Nanopartiküller ile Fotodinamik Tedavi antikanser Etkinliği

Photodynamic therapy (PDT) is a non-invasive and non-surgical method representing an attractive alternative choice for lung cancer treatment. ...

Kanser Araştırmaları

Facile Preparation of Internally Self-assembled Lipid Particles Stabilized by Carbon Nanotubes

We present a facile method to prepare nanostructured lipid particles stabilized by carbon nanotubes (CNTs). Single-walled (pristine) and multi-walled (functionalized) CNTs are used as stabilizers to produce Pickering type oil-in-water (O/W) emulsions. Lipids namely, Dimodan U and Phytantriol are used as emulsifiers, which in excess water self-assemble into the bicontinuous cubic Pn3m phase. This highly viscous phase is fragmented into smaller particles using a probe ultrasonicator in presence of conventional surfactant stabilizers or CNTs as done here. Initially, the CNTs (powder form) are dispersed in water followed by further ultrasonication with the molten lipid to form the final emulsion. During this process the CNTs get coated with lipid molecules, which in turn are presumed to surround the lipid droplets to form a particulate emulsion that is stable for months. The average size of CNT-stabilized nanostructured lipid particles is in the submicron range, which compares well with the particles stabilized using conventional surfactants. Small angle X-ray scattering data confirms the retention of the original Pn3m cubic phase in the CNT-stabilized lipid dispersions as compared to the pure lipid phase (bulk state). Blue shift and lowering of the intensities in characteristic G and G&#39; bands of CNTs observed in Raman spectroscopy characterize the interaction between CNT surface and lipid molecules. These results suggest that the interactions between the CNTs and lipids are responsible for their mutual stabilization in aqueous solutions. As the concentrations of CNTs employed for stabilization are very low and lipid molecules are able to functionalize the CNTs, the toxicity of CNTs is expected to be insignificant while their biocompatibility is greatly enhanced. Hence the present approach finds a great potential in various biomedical applications, for instance, for developing hybrid nanocarrier systems for the delivery of multiple functional molecules as in combination therapy or polytherapy.

We report on a smart application of carbon nanotubes for kinetic stabilization of lipid particles that contain self-assembled nanostructures in their cores. The preparation of lipid particles requires rather low concentrations of carbon nanotubes permitting their use in biomedical applications such as drug delivery.

Karbon Nanotüpler tarafından Stabilize İçeriden Kendinden monte Lipid Parçacıklar uyduruk hazırlanması

We present a facile method to prepare nanostructured lipid particles stabilized by carbon nanotubes (CNTs). Single-walled (pristine) and multi-walled ...

Kimya

Custom-designed Laser-based Heating Apparatus for Triggered Release of Cisplatin from Thermosensitive Liposomes with Magnetic Resonance Image Guidance

Liposomes have been employed as drug delivery systems to target solid tumors through exploitation of the enhanced permeability and retention (EPR) effect resulting in significant reductions in systemic toxicity. Nonetheless, insufficient release of encapsulated drug from liposomes has limited their clinical efficacy. Temperature-sensitive liposomes have been engineered to provide site-specific release of drug in order to overcome the problem of limited tumor drug bioavailability. Our lab has designed and developed a heat-activated thermosensitive liposome formulation of cisplatin (CDDP), known as HTLC, to provide triggered release of CDDP at solid tumors. Heat-activated delivery in vivo was achieved in murine models using a custom-built laser-based heating apparatus that provides a conformal heating pattern at the tumor site as confirmed by MR thermometry (MRT). A fiber optic temperature monitoring device was used to measure the temperature in real-time during the entire heating period with online adjustment of heat delivery by alternating the laser power. Drug delivery was optimized under magnetic resonance (MR) image guidance by co-encapsulation of an MR contrast agent (i.e.,&#160;gadoteridol) along with CDDP into the thermosensitive liposomes as a means to validate the heating protocol and to assess tumor accumulation. The heating protocol consisted of a preheating period of 5 min prior to administration of HTLC and 20 min heating post-injection. This heating protocol resulted in effective release of the encapsulated agents with the highest MR signal change observed in the heated tumor in comparison to the unheated tumor and muscle. This study demonstrated the successful application of the laser-based heating apparatus for preclinical thermosensitive liposome development and the importance of MR-guided validation of the heating protocol for optimization of drug delivery.

AN MRI-compatible&#160;custom-designed laser-based heating apparatus has been developed to provide local heating of subcutaneous tumors in order to activate release of agents from thermosensitive liposomes specifically at the tumor region.

Manyetik Rezonans Görüntü Rehberlik ile Termosensitif Lipozomlu gelen Sisplatinin Tetikleme Release için özel tasarlanmış Lazer-bazlı ısıtma Aparatı

Liposomes have been employed as drug delivery systems to target solid tumors through exploitation of the enhanced permeability and retention (EPR) effect ...

Biyomühendislik

Preparation and Characterization of Lipophilic Doxorubicin Pro-drug Micelles

Micelles have been successfully used for the delivery of anticancer drugs. Amphiphilic polymers form core-shell structured micelles in an aqueous environment through self-assembly. The hydrophobic core of micelles functions as a drug reservoir and encapsulates hydrophobic drugs. The hydrophilic shell prevents the aggregation of micelles and also prolongs their systemic circulation in vivo. In this protocol, we describe a method to synthesize a doxorubicin lipophilic pro-drug, doxorubicin-palmitic acid (DOX-PA), which will enhance drug loading into micelles. A pH-sensitive hydrazone linker was used to conjugate doxorubicin with the lipid, which facilitates the release of free doxorubicin inside cancer cells. Synthesized DOX-PA was purified with a silica gel column using dichloromethane/methanol as the eluent. Purified DOX-PA was analyzed with thin layer chromatography (TLC) and 1H-Nuclear Magnetic Resonance Spectroscopy (1H-NMR). A film dispersion method was used to prepare DOX-PA loaded DSPE-PEG micelles. In addition, several methods for characterizing micelle formulations are described, including determination of DOX-PA concentration and encapsulation efficiency, measurement of particle size and distribution, and assessment of in vitro anticancer activities. This protocol provides useful information regarding the preparation and characterization of drug-loaded micelles and thus will facilitate the research and development of novel micelle-based cancer nanomedicines.

A protocol for the preparation and characterization of lipophilic doxorubicin pro-drug loaded 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPE-PEG) micelles is described.

Lipofilik Doksorubisin Pro-ilaç misellerin Hazırlanması ve Karakterizasyonu

Micelles have been successfully used for the delivery of anticancer drugs. Amphiphilic polymers form core-shell structured micelles in an aqueous ...

Phase Change Dimethyldioctadecylammonium-Shelled Microdroplets as a Promising Drug Delivery System: Results on 3D Spheroids of Mammalian Tumor Cells

Significant improvement of phase-change perfluorocarbon microdroplets (MDs) in the vast theranostic scenario passes through the optimization of the MDs composition with respect to synthesis efficiency, stability, and drug delivery capability. To this aim, decafluoropentane (DFP) MDs stabilized by a shell of dimethyldioctadecylammonium bromide (DDAB) cationic surfactant were designed. A high concentration of DDAB-MDs was readily obtained within a few seconds by pulsed high-power insonation, resulting in low polydisperse 1 &#181;m size droplets. Highly positive &#950;-potential, together with a long, saturated hydrocarbon chains of the DDAB shell, are key factors to stabilize the droplet and the drug cargo therein. The high affinity of the DDAB shell with cell plasma membrane allows for localized chemotherapeutics delivery by increasing the drug concentration at the tumor cell interface and boosting the uptake. This would turn DDAB-MDs into a relevant drug delivery tool exhibiting high antitumor activity at very low drug doses.
In this work, the efficacy of such an approach is shown to dramatically improve the effect of doxorubicin against 3D spheroids of mammalian tumor cells, MDA-MB-231. The use of&#160;three-dimensional (3D) cell cultures developed in the form of multicellular tumor spheroids (i.e., densely packed cells in a spherical shape) has numerous advantages compared to 2D cell cultures: in addition to have the potential to bridge the gap between conventional in vitro studies and animal testing, it will improve the ability to perform more predictive in vitro screening assays for preclinical drug development or evaluate the potential of off-label drugs and new co-targeting strategies.

<meta charset="utf8"></head><body>Umut Verici Bir İlaç Dağıtım Sistemi Olarak Faz Değişimli Dimetildioktadeilamonyum Kabuklu Mikro Damlacıklar: Memeli Tümör Hücrelerinin 3D Sferoidleri Üzerine Sonu

Decafluoropentane microdroplets developed with a shell of dimethyldioctadecylammonium bromide exhibited an exceptional colloidal stability and an actractive biointerface. DDAB-MDs proved to be efficient drug reservoirs characterized by a high affinity to plasma membranes together with enhanced uptake and antitumor activity of Doxorubicin against human triple-negative breast cancer (MDA-MB-231) 3D model.

Umut Verici Bir İlaç Dağıtım Sistemi Olarak Faz Değişimli Dimetildioktadeilamonyum Kabuklu Mikro Damlacıklar: Memeli Tümör Hücrelerinin 3D Sferoidleri Üzerine Sonuçlar

Significant improvement of phase-change perfluorocarbon microdroplets (MDs) in the vast theranostic scenario passes through the optimization of the MDs ...

Targeted Plasma Membrane Delivery of a Hydrophobic Cargo Encapsulated in a Liquid Crystal Nanoparticle Carrier

The controlled delivery of drug/imaging agents to cells is critical for the development of therapeutics and for the study of cellular signaling processes. Recently, nanoparticles (NPs) have shown significant promise in the development of such delivery systems. Here, a liquid crystal NP (LCNP)-based delivery system has been employed for the controlled delivery of a water-insoluble dye, 3,3&#8242;-dioctadecyloxacarbocyanine perchlorate (DiO), from within the NP core to the hydrophobic region of a plasma membrane bilayer. During the synthesis of the NPs, the dye was efficiently incorporated into the hydrophobic LCNP core, as confirmed by multiple spectroscopic analyses. Conjugation of a PEGylated cholesterol derivative to the NP surface (DiO-LCNP-PEG-Chol) enabled the binding of the dye-loaded NPs to the plasma membrane in HEK 293T/17 cells. Time-resolved laser scanning confocal microscopy and F&#246;rster resonance energy transfer (FRET) imaging confirmed the passive efflux of DiO from the LCNP core and its insertion into the plasma membrane bilayer. Finally, the delivery of DiO as a LCNP-PEG-Chol attenuated the cytotoxicity of DiO; the NP form of DiO exhibited ~30-40% less toxicity compared to DiOfree delivered from bulk solution. This approach demonstrates the utility of the LCNP platform as an efficient modality for the membrane-specific delivery and modulation of hydrophobic molecular cargos.

A liquid crystal nanoparticle (LCNP) nanocarrier is exploited as a vehicle for the controlled delivery of a hydrophobic cargo to the plasma membrane of living cells.

Sıvı Kristal Nanopartikül Carrier bir Hidrofobik Kargo Encapsulated, hedeflenen Plazma Zarı Teslimat

The controlled delivery of drug/imaging agents to cells is critical for the development of therapeutics and for the study of cellular signaling processes. ...

Formulation and Characterization of Bioactive Agent Containing Nanodisks

The term nanodisk refers to a discrete type of nanoparticle comprised of a bilayer forming lipid, a scaffold protein, and an integrated bioactive agent. Nanodisks are organized as a disk-shaped lipid bilayer whose perimeter is circumscribed by the scaffold protein, usually a member of the exchangeable apolipoprotein family. Numerous hydrophobic bioactive agents have been efficiently solubilized in nanodisks by their integration into the hydrophobic milieu of the particle&#39;s lipid bilayer, yielding a largely homogenous population of particles in the range of 10-20 nm in diameter. The formulation of nanodisks requires a precise ratio of individual components, an appropriate sequential addition of each component, followed by bath sonication of the formulation mixture. The amphipathic scaffold protein spontaneously contacts and reorganizes the dispersed bilayer forming lipid/bioactive agent mixture to form a discrete, homogeneous population of nanodisk&#160;particles. During this process, the reaction mixture transitions from an opaque, turbid appearance to a clarified sample that, when fully optimized, yields no precipitate upon centrifugation. Characterization studies involve the determination of bioactive agent solubilization efficiency, electron microscopy, gel filtration chromatography, ultraviolet visible (UV/Vis) absorbance spectroscopy, and/or fluorescence spectroscopy. This is normally followed by an investigation of biological activity using cultured cells or mice. In the case of nanodisks harboring an antibiotic (i.e., the macrolide polyene antibiotic amphotericin B), their ability to inhibit the growth of yeast or fungi as a function of concentration or time can be measured. The relative ease of formulation, versatility with respect to component parts, nanoscale particle size, inherent stability, and aqueous solubility permits myriad in vitro and in vivo applications of nanodisk technology. In the present article, we describe a general methodology to formulate and characterize nanodisks containing amphotericin&#160;B as the hydrophobic bioactive agent.

Here, we describe the production and characterization of bioactive agents containing nanodisks. Amphotericin B nanodisks are taken as an example to describe the protocol in a stepwise manner.

Nanodisk İçeren Biyoaktif Ajanın Formülasyonu ve Karakterizasyonu

The term nanodisk refers to a discrete type of nanoparticle comprised of a bilayer forming lipid, a scaffold protein, and an integrated bioactive agent. ...

Biyokimya

Uptake of New Lipid-coated Nanoparticles Containing Falcarindiol by Human Mesenchymal Stem Cells

Nanoparticles are the focus of an increased interest in drug delivery systems for cancer therapy. Lipid-coated nanoparticles are inspired in structure and size by low-density lipoproteins (LDLs) because cancer cells have an increased need for cholesterol to proliferate, and this has been exploited as a mechanism for delivering anticancer drugs to cancer cells. Moreover, depending on drug chemistry, encapsulating the drug can be advantageous to avoid degradation of the drug during circulation in vivo. Therefore, in this&#160;study, this design is used to fabricate lipid-coated nanoparticles of the anticancer drug falcarindiol, providing a potential new delivery system of falcarindiol in order to stabilize its chemical structure against degradation and improve its uptake by tumors. Falcarindiol nanoparticles, with a phospholipid and cholesterol monolayer encapsulating the purified drug core of the particle, were designed. The lipid monolayer coating consists of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol (Chol), and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE PEG 2000) along with the fluorescent label DiI (molar ratios of 43:50:5:2). The nanoparticles are fabricated using the rapid injection method, which is a fast and simple technique to precipitate nanoparticles by good-solvent for anti-solvent exchange. It consists of a rapid injection of an ethanol solution containing the nanoparticle components into an aqueous phase. The size of the fluorescent nanoparticles is measured using dynamic light scattering (DLS) at 74.1 &#177; 6.7 nm. The uptake of the nanoparticles is tested in human mesenchymal stem cells (hMSCs) and imaged using fluorescence and confocal microscopy. The uptake of the nanoparticles is observed in hMSCs, suggesting the potential for such a stable drug delivery system for falcarindiol.

This article describes the encapsulation of falcarindiol in lipid-coated 74 nm nanoparticles. The cellular uptake of the nanoparticles&#160;by human stem cells into lipid droplets is monitored by fluorescent and confocal imaging. Nanoparticles are fabricated by the rapid injection method of solvent shifting, and their size is measured with the dynamic light scattering technique.

Falcarindiol tarafından insan mezenkimal kök hücre içeren yeni Lipid kaplı nano tanecikleri alımını

Nanoparticles are the focus of an increased interest in drug delivery systems for cancer therapy. Lipid-coated nanoparticles are inspired in structure and ...

Preparation and Characterization of Nanoliposomes for the Entrapment of Bioactive Hydrophilic Globular Proteins

Liposome nanocapsules have been applied for many purposes in the pharmaceutical, cosmetic, and food industries. Attributes of liposomes include their biocompatibility, biodegradability, non-immunogenicity, non-toxicity, and ability to entrap both hydrophilic and hydrophobic compounds. The classical hydration of thin lipid films in an organic solvent is applied herein as a technique to encapsulate tarin, a plant lectin, in nanoliposomes. Nanoliposome size, stability, entrapment efficiency, and morphological characterization are described in detail. The nanoliposomes are prepared using 1,2-dioleoyl-sn-glycerol-3-phosphoethanolamine (DOPE), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (ammonium salt; DSPE-MPEG 2000), and cholesterylhemisuccinate (CHEMS) as the main constituents. Lipids are first dissolved in chloroform to obtain a thin lipid film that is subsequently rehydrated in ammonium sulfate solution containing the protein to be entrapped and incubated overnight. Then, sonication and extrusion techniques are applied to generate nanosized unilamellar vesicles. The size and polydispersity index of the nanovesicles are determined by dynamic light scattering, while nanovesicle morphology is assessed by scanning electron microscopy. Entrapment efficiency is determined by the ratio of the amount of unencapsulated protein to original amount of initially loaded protein. Homogeneous liposomes are obtained with an average size of 155 nm and polydispersity index value of 0.168. A high entrapment efficiency of 83% is achieved.

This study describes classical hydration using the thin lipid film method for nanoliposome preparation followed by nanoparticle characterization. A 47 kDa-hydrophilic and globular protein, tarin, is successfully encapsulated as a strategy to improve stability, avoid fast clearance, and promote controlled release. The method can be adapted to hydrophobic molecules encapsulation.

Biyoaktif Hidrofilik Globüler Proteinlerin Tuzakları Için Nanoliposomes Hazırlanması ve Karakterizasyonu

Liposome nanocapsules have been applied for many purposes in the pharmaceutical, cosmetic, and food industries. Attributes of liposomes include their ...

Nano yapılı lipid taşıyıcı kullanılarak kanser terapötik dakarbazin kapsüllenmesi

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