Gli autori riconoscono la borsa di studio Arabia Saudita-finanziato (I821) per aver reso possibile la ricerca. Gli autori sono grati al dott Xianwei Liu per il supporto di esperti in analisi TEM presso la Cranfield University.

1. Preparazione di emulsioni olio-in-acqua <ol><li> Pesare gliceril palmitostearato (120 mg), isopropilmiristato (60 mg), D-α-tocoferolo polietilene glicole succinato (30 mg) e lecitina di soia (30 mg), e aggiungerli al 12,5 ml di solventi organici (6,25 ml di acetone e 6,25 ml di etanolo). sciogliere rapidamente la miscela alla temperatura di 70 ° C (5 ° C sopra il punto di fusione del lipide solido) in bagno d&#39;acqua. </li><li> Aggiungere sia 125, 250 o 375 mg di Poloxamer188 in 12,5 ml di DDH 2 O per ottenere 1-3% (rispettivamente) Poloxamer 188 soluzione, che è soggetto a riscaldamento alla stessa temperatura come sopra. </li><li> Aggiungere la soluzione fase acquosa dalla fase 1.2 alla soluzione fase olio dal punto 1.1 a gocce per formare emulsioni sotto agitazione magnetica a 400 rpm. Mescolare l&#39;emulsione a 400 rpm per altri 4 ore per consentire l&#39;evaporazione dei solventi organici. </li></ol> 2. solidificazione e omogeneizzazione <ol><li> lasciare tha emulsione in una stanza fredda (4 ° C) per 2 ore a solidificare / cristallizzare. </li><li> Per ottenere NLC, sottoporre l&#39;emulsione di elevata dispersione pura (HSD), con un omogeneizzatore a 10.000-15.000 rpm per 10-40 min. </li></ol> 3. Ottimizzazione del NLC Preparazione <ol><li> Prelevare campioni dal punto 2.2 con una concentrazione di tensioattivo di 1, 2 e 3% sottoposti HSD a velocità di 10.000, 15.000 e 20.000 rpm, rispettivamente, e gli intervalli di tempo di 10, 20, 30 e 40 minuti, rispettivamente, </li><li> Esaminare i campioni per dimensione delle particelle (PS), poli indice di dispersione (PDI), morfologia e ultrastruttura 20. Nota: I parametri che producono particelle con il più piccolo formato (155 nm) e il valore di PDI (0,2) sono determinati come ottimale. </li></ol> 4. Preparazione di Dac-caricato NLC (NLC-Dac) <ol><li> Preparare la soluzione fase olio come descritto al punto 1.1 con l&#39;aggiunta di Dac (70 mg) prima sciogliendo la miscela a 70 ° C a bagnomaria. </li><li> Prepare una soluzione fase acquosa come descritto al punto 1.2 con 1% di tensioattivo, e aggiungere questa soluzione a quello preparato nella fase 4.1 a gocce per formare una emulsione sotto agitazione magnetica a 400 rpm. Mescolare l&#39;emulsione per ulteriori 4 ore per evaporare i solventi organici. </li><li> Lasciare l&#39;emulsione in una stanza fredda (4 ° C) per 2 ore a solidificare / cristallizzare come descritto al punto 2, e, infine, sottoporre l&#39;emulsione di elevata dispersione pura (HSD) utilizzando i parametri ottimali determinati nella fase 3. </li></ol>

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<li>Ding, B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Biodegradable+methoxy+poly+%28ethylene+glycol%29-poly+%28lactide%29+nanoparticles+for+controlled+delivery+of+dacarbazine%3A+Preparation%2C+characterization+and+anticancer+activity+evaluation%5BTitle%5D)+AND+%22Afr+J+Pharm+Pharacol%22%5BJournal%5D)">Biodegradable methoxy poly (ethylene glycol)-poly (lactide) nanoparticles for controlled delivery of dacarbazine: Preparation, characterization and anticancer activity evaluation.</a> Afr J Pharm Pharacol. 5 (11), 1369-1377 (2011).</li>
<li>Ding, B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Anti-DR5+monoclonal+antibody-mediated+DTIC-loaded+nanoparticles+combining+chemotherapy+and+immunotherapy+for+malignant+melanoma%3A+target+formulation+development+and+in+vitro+anticancer+activity%5BTitle%5D)+AND+%22Int+J+Nanomedicine%22%5BJournal%5D)">Anti-DR5 monoclonal antibody-mediated DTIC-loaded nanoparticles combining chemotherapy and immunotherapy for malignant melanoma: target formulation development and in vitro anticancer activity.</a> Int J Nanomedicine. 6, 1991-2005 (2011).</li>
<li>Jenning, V., Thünemann, A. F., Gohla, S. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Characterisation+of+a+novel+solid+lipid+nanoparticle+carrier+system+based+on+binary+mixtures+of+liquid+and+solid+lipids%5BTitle%5D)+AND+%22Int+J+Pharm%22%5BJournal%5D)">Characterisation of a novel solid lipid nanoparticle carrier system based on binary mixtures of liquid and solid lipids.</a> Int J Pharm. 199 (2), 167-177 (2000).</li>
<li>Müller, R. H., Radtke, M., Wissing, S. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Nanostructured+lipid+matrices+for+improved+microencapsulation+of+drugs%5BTitle%5D)+AND+%22Int+J+Pharm%22%5BJournal%5D)">Nanostructured lipid matrices for improved microencapsulation of drugs.</a> Int J Pharm. 242 (1-2), 121-128 (2002).</li>
<li>Pouton, C. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Lipid+formulations+for+oral+administration+of+drugs%3A+Non-emulsifying%2C+self-emulsifying+and+%27self-microemulsifying%27+drug+delivery+systems%5BTitle%5D)+AND+%22Eur.+J.+Pharm.+Sci%22%5BJournal%5D)">Lipid formulations for oral administration of drugs: Non-emulsifying, self-emulsifying and 'self-microemulsifying' drug delivery systems.</a> Eur. J. Pharm. Sci. 11 (Suppl. 2), S93-S98 (2000).</li>
<li>Jores, K., Mehnert, W., Drechsler, M., Bunjes, H., Johann, C., Mäder, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Investigations+on+the+structure+of+solid+lipid+nanoparticles+%28SLN%29+and+oil-loaded+solid+lipid+nanoparticles+by+photon+correlation+spectroscopy%2C+field-flow+fractionation+and+transmission+electron+microscopy%5BTitle%5D)+AND+%22J+Controlled+Release%22%5BJournal%5D)">Investigations on the structure of solid lipid nanoparticles (SLN) and oil-loaded solid lipid nanoparticles by photon correlation spectroscopy, field-flow fractionation and transmission electron microscopy.</a> J Controlled Release. 95 (2), 217-227 (2004).</li>
<li>Almousallam, M., Zhu, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Encapsulation+of+cancer+therapeutic+agent+dacarbazine+using+nanostructured+lipid+carrier%5BTitle%5D)+AND+%22Int+nano+lett%22%5BJournal%5D)">Encapsulation of cancer therapeutic agent dacarbazine using nanostructured lipid carrier.</a> Int nano lett. , (2015).</li>
<li>Ng, W. K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Thymoquinone-loaded+nanostructured+lipid+carrier+exhibited+cytotoxicity+towards+breast+cancer+cell+lines+%28MDA-MB-231+and+MCF-7%29+and+cervical+cancer+cell+lines+%28HeLa+and+SiHa%29%5BTitle%5D)+AND+%22BioMed+Research+International%22%5BJournal%5D)">Thymoquinone-loaded nanostructured lipid carrier exhibited cytotoxicity towards breast cancer cell lines (MDA-MB-231 and MCF-7) and cervical cancer cell lines (HeLa and SiHa).</a> BioMed Research International. , (2015).</li>
<li>Sun, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Quercetin-nanostructured+lipid+carriers%3A+Characteristics+and+anti-breast+cancer+activities+in+vitro%5BTitle%5D)+AND+%22Colloids+Surf.%2C+B%22%5BJournal%5D)">Quercetin-nanostructured lipid carriers: Characteristics and anti-breast cancer activities in vitro.</a> Colloids Surf., B. 113, 15-24 (2014).</li>
<li>Savla, R., Garbuzenko, O. B., Chen, S., Rodriguez-Rodriguez, L., Minko, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Tumor-Targeted+Responsive+Nanoparticle-Based+Systems+for+Magnetic+Resonance+Imaging+and+Therapy%5BTitle%5D)+AND+%22Pharm+Res%22%5BJournal%5D)">Tumor-Targeted Responsive Nanoparticle-Based Systems for Magnetic Resonance Imaging and Therapy.</a> Pharm Res. 31 (12), 3487-3502 (2014).</li>
<li>Chen, Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Formulation%2C+characterization%2C+and+evaluation+of+in+vitro+skin+permeation+and+in+vivo+pharmacodynamics+of+surface-charged+tripterine-loaded+nanostructured+lipid+carriers%5BTitle%5D)+AND+%22Int+J+Nanomedicine%22%5BJournal%5D)">Formulation, characterization, and evaluation of in vitro skin permeation and in vivo pharmacodynamics of surface-charged tripterine-loaded nanostructured lipid carriers.</a> Int J Nanomedicine. 7, 3023(2012).</li>
<li>Sanna, V., Caria, G., Mariani, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Effect+of+lipid+nanoparticles+containing+fatty+alcohols+having+different+chain+length+on+the+ex+vivo+skin+permeability+of+Econazole+nitrate%5BTitle%5D)+AND+%22Powder+Technol%22%5BJournal%5D)">Effect of lipid nanoparticles containing fatty alcohols having different chain length on the ex vivo skin permeability of Econazole nitrate.</a> Powder Technol. 201 (1), 32-36 (2010).</li>
<li>Brigger, I., Dubernet, C., Couvreur, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Nanoparticles+in+cancer+therapy+and+diagnosis%5BTitle%5D)+AND+%22Adv+Drug+Deliv+Rev%22%5BJournal%5D)">Nanoparticles in cancer therapy and diagnosis.</a> Adv Drug Deliv Rev. 54 (5), 631-651 (2002).</li>
<li>Visaria, R. K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Enhancement+of+tumor+thermal+therapy+using+gold+nanoparticle-assisted+tumor+necrosis+factor-a+delivery%5BTitle%5D)+AND+%22Mol+Cancer+Ther%22%5BJournal%5D)">Enhancement of tumor thermal therapy using gold nanoparticle-assisted tumor necrosis factor-a delivery.</a> Mol Cancer Ther. 5 (4), 1014-1020 (2006).</li>
<li>Tripathi, A., Gupta, R., Saraf, S. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((PLGA+nanoparticles+of+anti+tubercular+drug%3A+Drug+loading+and+release+studies+of+a+water+in-soluble+drug%5BTitle%5D)+AND+%22Int+J+PharmTech+Res%22%5BJournal%5D)">PLGA nanoparticles of anti tubercular drug: Drug loading and release studies of a water in-soluble drug.</a> Int J PharmTech Res. 2 (3), 2116-2123 (2010).</li>
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<li>Lei, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Dual+drug+encapsulation+in+a+novel+nano-vesicular+carrier+for+the+treatment+of+cutaneous+melanoma%3A+Characterization+and+in+vitro%2Fin+vivo+evaluation%5BTitle%5D)+AND+%22RSC+Advances%22%5BJournal%5D)">Dual drug encapsulation in a novel nano-vesicular carrier for the treatment of cutaneous melanoma: Characterization and in vitro/in vivo evaluation.</a> RSC Advances. 5 (26), (2015).</li>
</ol>

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particelle nanostrutturati a base di lipidi sono stati utilizzati per fornire un supporto altamente lipofilo per la consegna dei farmaci idrofobici. Un NLC è la seconda generazione del vettore lipidico nanostrutturato solido, che sono solidi a temperatura ambientale e del corpo. L&#39;incorporazione di un lipide solido in un lipide liquido in un risultato NLC in una cristallizzazione meno perfetta, aumentando così l&#39;efficienza droga carico e riducendo anche l&#39;espulsione di farmaci incapsulati durante la conser...

Dacarbazina (DAC) è un agente alchilante che esercita l&#39;attività anti-tumorale attraverso acidi nucleici metilazione del DNA o danni diretti, portando ad arresto del ciclo cellulare e la morte cellulare 1. Come primo agente chemioterapico linea, Dac è stato usato da solo o in combinazione con altri farmaci chemioterapici per il trattamento di vari cancri 2-6. Esso è l&#39;agente più attivo finora usato nel trattamento di melanoma cutaneo e metastatico, che è la forma più aggressiva di 3,7,8 cancro della pelle. Il tasso di risposta, tuttavia, è solo il 20% al massimo, e gli effetti terapeutici sono spesso accompagnate da gravi effetti collaterali sistemici. Nella sua forma naturale, DAC è idrofilo ed è instabile a causa della sua fotosensibilità 9. L&#39;unica formula disponibile per uso clinico attualmente è una polvere sterile per essere utilizzato in sospensione per via endovenosa 7,8 infusione. Il basso tasso di risposta ed elevata tossicità sistemica rmangiato del farmaco è in gran parte attribuibile alla sua scarsa solubilità in acqua, quindi a basso disponibilità al sito di destinazione, e alta la distribuzione in siti non bersaglio, che limita la dose massima del farmaco 10. La rapida degradazione e metabolismo dopo il ricovero endovenosa insieme allo sviluppo di resistenza ai farmaci limitano l&#39;applicazione clinica ed effetto terapeutico del farmaco 11. Pertanto, non vi è un urgente bisogno di sviluppare formulazioni alternative DAC per il trattamento di melanoma maligno. Sistemi colloidali contenenti liposomi, micelle o particelle nanostrutturate sono stati intensamente studiati per il loro uso nella somministrazione di farmaci come recensito da Marilene et al. 12 particelle nanostrutturati come portatori potenziali di farmaci sono state attirando sempre maggiore attenzione negli ultimi dieci anni a causa della loro capacità di aumentare carico di droga efficienza, controllo di rilascio del farmaco, migliorare la farmacocinetica di droga e la biodistribuzione, e quindi restrarre droga tossicità sistemica 13. Solo pochi nanoformulazioni, tuttavia, sono state studiate finora per la consegna Dac, che mostra la protezione del farmaco dal foto degenerazione, maggiore solubilità della droga, e migliorato effetto terapeutico 10,14,15. Tuttavia queste formulazioni sofferto di scarsa efficienza di incapsulamento, mentre alcuni anche utilizzando nanoparticelle polimeriche di sintesi che non sono convenienti. Vettori nanostrutturati lipidici (NLC), costituiti da una miscela di lipidi solidi e liquidi, sono stati sviluppati per drug delivery 16,17. I farmaci devono essere incapsulate sono spesso solubili in entrambi i lipidi liquidi e fasi lipidi solidi 18, con un conseguente elevato carico e rilascio controllato 19. Questo studio mira a sviluppare una nuova formulazione Dac sulla base di NLC-incapsulamento utilizzando gliceril palmitostearato e isopropilmiristato come lipidi. La preparazione coinvolti olio in emulsione acquosa, evaporazione, solidificazione, e homogenization. I preparativi sono stati caratterizzati per la dimensione NLC, forma, ultrastruttura e dispersity, l&#39;efficienza di incapsulamento di droga e di carico di droga 20.

<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

L&#39;unica formula di dacarbazina (DAC) in uso clinico è l&#39;infusione endovenosa, presenta un profilo terapeutico povero a causa della bassa dispersità del farmaco in soluzione acquosa. Per ovviare a questo, un vettore nanostrutturato lipidica (NLC) costituito gliceril palmitostearato e isopropil miristato è stato sviluppato per incapsulare Dac. NLCS con dimensione controllata sono stati raggiunti con elevata dispersione di taglio (HSD) dopo la solidificazione di emulsione di olio in acqua. I parametri di sintesi, tra cui la concentrazione di tensioattivi, la velocità e il tempo di HSD sono stati ottimizzati per ottenere il NLC più piccolo con la dimensione, indice di polidispersione e potenziale zeta di 155 ± 10 nm, 0,2 ± 0,01, e -43,4 ± 2 mV, rispettivamente. I parametri ottimali sono stati anche impiegati per la preparazione NLC DAC-caricato. Il CNT risultante caricato con Dac possedeva dimensioni, l&#39;indice di polidispersione e potenziale zeta di 190 ± 10 nm, 0,2 ± 0,01, e -43,5 ± 1,2 mV, rispettivamente. L&#39;ef incapsulamento della drogaFICIENCY e caricamento del farmaco ha raggiunto il 98% e il 14% rispettivamente. Questo è il primo rapporto sulla incapsulamento del Dac utilizzando NLC, il che implica che NLC potrebbe essere un nuovo candidato potenziale come vettore di droga per migliorare il profilo terapeutico di Dac.

I preparativi della NLC e NLC-Dac utilizzando gliceril palmitostearato e isopropilmiristato con diversi parametri sono stati caratterizzati per PS, PDI, morfologia e ultrastruttura 20. Il PS e PDI del NLCS erano concentrazione di tensioattivi, la velocità HSD e la durata dipendente. Come giudicato da PS e PDI del NLCS, i migliori risultati sono stati ottenuti con 1% di tensioattivo e una velocità di dispersione pura di 15.000 rpm per 30 min (Figura 1A, <stro...

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

Il metodo più comunemente utilizzato per nanostrutturato carrier lipidico sintesi (NLC) coinvolge olio in emulsione acquosa, omogeneizzazione e solidificazione. Questo è stato modificato qui applicando alta dispersione di taglio dopo la solidificazione di raggiungere un NLC con la dimensione auspicabile, una migliore incapsulamento di droga e l&#39;efficienza farmaco carico come un potenziale vettore per la consegna dacarbazina.

Incapsulamento del Cancro agente terapeutico dacarbazina Utilizzando Nanostrutturati Lipid Carrier

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 Views.  Cranfield University.  Il metodo più comunemente utilizzato per nanostrutturato carrier lipidico sintesi (NLC) coinvolge olio in emulsione acquosa, omogeneizzazione e solidificazione. Questo è stato modificato qui applicando alta dispersione di taglio dopo la solidificazione di raggiungere un NLC con la dimensione auspicabile, una migliore incapsulamento di droga e l'efficienza farmaco carico come un potenziale vettore per la consegna dacarbazina. 

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.

Anticancro Efficacia della terapia fotodinamica con cancro del polmone con targeting nanoparticelle

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

Ricerca

Ricerca sul cancro

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.

Preparazione facile di Internamente auto-assemblato Lipid particelle stabilizzati da nanotubi di carbonio

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

Chimica

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.

Appositamente studiata apparecchi di riscaldamento a base laser per la Release Innescata di Cisplatino da termosensibile liposomi con Risonanza Magnetica Guidance Immagine

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

Bioingegneria

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.

Preparazione e caratterizzazione di lipofila doxorubicina micelle pro-farmaco

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>Microgoccioline sgusciate di dimetildiottadecilammonio a cambiamento di fase come promettente sistema di somministrazione di farmaci: risultati su sferoidi 3D di c

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.

Microgoccioline sgusciate di dimetildiottadecilammonio a cambiamento di fase come promettente sistema di somministrazione di farmaci: risultati su sferoidi 3D di cellule tumorali di mammifero

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.

Targeted membrana plasmatica di consegna di un idrofobo Cargo incapsulato in un cristallo nanoparticelle Carrier Liquid

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.

Formulazione e caratterizzazione di agenti bioattivi contenenti nanodischi

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

Biochimica

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.

Assorbimento di nuove nanoparticelle rivestite con lipidi contenenti Falcarindiol di cellule staminali mesenchimali umane

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.

Preparazione e caratterizzazione dei nanoliposomi per l'entratura delle proteine globulari bioattive

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

Incapsulamento del Cancro agente terapeutico dacarbazina Utilizzando Nanostrutturati Lipid Carrier

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