Pluronic F‐127: An Efficient Delivery Vehicle for 3‐(1'‐hexyloxy)ethyl‐3‐devinylpyropheophorbide‐a (HPPH or Photochlor)

2019 ◽  
Vol 96 (3) ◽  
pp. 625-635 ◽  
Author(s):  
Joseph Cacaccio ◽  
Farukh Durrani ◽  
Ravindra R. Cheruku ◽  
Ballav Borah ◽  
Manivannan Ethirajan ◽  
...  
Peptides ◽  
2010 ◽  
Vol 31 (8) ◽  
pp. 1421-1425 ◽  
Author(s):  
Hidenori Takagi ◽  
Takachika Hiroi ◽  
Sakiko Hirose ◽  
Lijun Yang ◽  
Fumio Takaiwa

Pharmaceutics ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 220 ◽  
Author(s):  
Eduard Figueras ◽  
Ana Martins ◽  
Adina Borbély ◽  
Vadim Le Joncour ◽  
Paola Cordella ◽  
...  

Tumor targeting has emerged as an advantageous approach to improving the efficacy and safety of cytotoxic agents or radiolabeled ligands that do not preferentially accumulate in the tumor tissue. The somatostatin receptors (SSTRs) belong to the G-protein-coupled receptor superfamily and they are overexpressed in many neuroendocrine tumors (NETs). SSTRs can be efficiently targeted with octreotide, a cyclic octapeptide that is derived from native somatostatin. The conjugation of cargoes to octreotide represents an attractive approach for effective tumor targeting. In this study, we conjugated octreotide to cryptophycin, which is a highly cytotoxic depsipeptide, through the protease cleavable Val-Cit dipeptide linker using two different self-immolative moieties. The biological activity was investigated in vitro and the self-immolative part largely influenced the stability of the conjugates. Replacement of cryptophycin by the infrared cyanine dye Cy5.5 was exploited to elucidate the tumor targeting properties of the conjugates in vitro and in vivo. The compound efficiently and selectively internalized in cells overexpressing SSTR2 and accumulated in xenografts for a prolonged time. Our results on the in vivo properties indicate that octreotide may serve as an efficient delivery vehicle for tumor targeting.


Author(s):  
Johanna Walther ◽  
Danny Wilbie ◽  
Vincent S.J. Tissingh ◽  
Mert Öktem ◽  
Heleen van der Veen ◽  
...  

The CRISPR-Cas9 system is an emerging therapeutic tool with the potential to correct diverse ge-netic disorders. However, for gene therapy applications an efficient delivery vehicle is required, capable of delivering the CRISPR-Cas9 components into the cytosol of the intended target cell population. Once there, the ribonucleoprotein complex (RNP) can be transported into the nucleus. Lipid nanoparticles (LNP) serve as promising candidates for delivery of CRISPR-Cas9 RNP. These delivery vehicles have been optimized for the delivery of nucleic acids, such as mRNA. Co-delivery of Cas9 encoding mRNA with the accompanying sgRNA leads to translation of the Cas9 protein and formation of the Cas9 RNP inside the cell. Only recently, direct delivery of the CRISPR-Cas9 RNP complexes has been explored, which requires adjustments to the LNP formulation. In this study, the importance of buffer composition and cationic charge during RNP and ssDNA en-trapment in LNP are demonstrated. After optimizing several formulation parameters, LNP were prepared that were colloidally stable in human plasma and efficiently deliver the SpCas9 RNP and ssDNA for HDR-correction in reporter cells. Under optimal formulation conditions, gene knock-out and gene correction efficiencies as high as 80% and 20%, respectively were achieved at nanomolar CRISPR-Cas9 RNP concentrations.


2019 ◽  
Vol 179 ◽  
pp. 128-135 ◽  
Author(s):  
Sabrina Belbekhouche ◽  
Julie Oniszczuk ◽  
André Pawlak ◽  
Imane El Joukhar ◽  
Angélique Goffin ◽  
...  

2021 ◽  
Author(s):  
Wenjuan Huang ◽  
Sijie Zhou ◽  
Bojiao Tang ◽  
Hongyan Xu ◽  
Xiaoxiao Wu ◽  
...  

2020 ◽  
Vol 27 ◽  
Author(s):  
Antonis D. Tsiailanis ◽  
Andreas G. Tzakos ◽  
Thomas Mavromoustakos

: Drugs have to overcome numerous barriers to reach their desired therapeutic targets. In several cases drugs, especially the highly lipophilic molecules, suffer from low solubility and bioavailability and therefore their desired targeting is hampered. In addition, undesired metabolic products might be produced or off-targets could be recognized. Along these lines, nanopharmacology has provided new technological platforms, to overcome these boundaries. Specifically, numerous vehicle platforms such as cyclodextrins and calixarenes have been widely utilized to host lipophilic drugs such as antagonists of the angiotensin II AT1 receptor (AT1R), as well as quercetin and silibinin. The encapsulation of these drugs in supramolecules or other systems refines their solubility and metabolic stability, increases their selectivity and therefore decreases their effective dose and improves the therapeutic index. In this minireview we report on the formulations of Silibinin and AT1R antagonist candesartan in a 2-HP-β-cyclodextrin host molecule, which displayed enhanced cytotoxicity and increased silibinin’s and candesartan’s stability, respectively. Moreover we describe the encapsulation of quercetin in gold nanoparticles bearing a calixarene supramolecular host. Also the encapsulation of temozolomide in a calixarene nanocapsule has been described. Finally, we report on the activity enhancement that has been achieved upon using these formulations as well as the analytical and computational methods we used to characterize these formulations and explore the molecular interactions between the host and quest molecules.


2018 ◽  
Vol 24 (1) ◽  
pp. 62-77 ◽  
Author(s):  
Sayed Sartaj Sohrab ◽  
Sherif Aly El-Kafrawy ◽  
Zeenat Mirza ◽  
Mohammad Amjad Kamal ◽  
Esam Ibraheem Azhar

Background: The MERS-CoV is a novel human coronavirus causing respiratory syndrome since April 2012. The replication of MERS-CoV is mediated by ORF 1ab and viral gene activity can be modulated by RNAi approach. The inhibition of virus replication has been documented in cell culture against multiple viruses by RNAi approach. Currently, very few siRNA against MERS-CoV have been computationally designed and published. Methods: In this review, we have discussed the computational designing and delivery of potential siRNAs. Potential siRNA can be designed to silence a desired gene by considering many factors like target site, specificity, length and nucleotide content of siRNA, removal of potential off-target sites, toxicity and immunogenic responses. The efficient delivery of siRNAs into targeted cells faces many challenges like enzymatic degradation and quick clearance through renal system. The siRNA can be delivered using transfection, electroporation and viral gene transfer. Currently, siRNAs delivery has been improved by using advanced nanotechnology like lipid nanoparticles, inorganic nanoparticles and polymeric nanoparticles. Conclusion: The efficacy of siRNA-based therapeutics has been used not only against many viral diseases but also against non-viral diseases, cancer, dominant genetic disorders, and autoimmune disease. This innovative technology has attracted researchers, academia and pharmaceuticals industries towards designing and development of highly effective and targeted disease therapy. By using this technology, effective and potential siRNAs can be designed, delivered and their efficacy with toxic effects and immunogenic responses can be tested against MERS-CoV.


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