Optical Methods for the Analysis of the Temoprofin Photosensitizer Distribution Between Serum Proteins and Methyl-β-Cyclodextrin Nanocarriers in Blood Serum

Yakavets, Ilya; Yankovsky, Igor; Khludeyev, I. I.; Lassalle, Henri-Pierre; Bezdetnaya, Lina; Zorin, Vladimir

doi:10.1007/s10812-018-0582-z

Cited by 7 publications

(9 citation statements)

References 17 publications

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“…The presence of mTHPC/CD complexes led to the increase of I 1 /I 2 ratio [14], demonstrating I 1 /I 2 = 0.88 and 1.00 for MD and TD, respectively, while in the case of Foslip ® , I 1 /I 2 was 0.8 (Figure 3b). At the same time, the high loading of mTHPC in the lipid bilayer resulted in fluorescence quenching [13,21], causing the decrease of FY, PIQ, and r values (Figure 3b, insert). Overall, 30% of mTHPC was encapsulated in CD complexes, while the fraction of PS in the lipid bilayer was 70%.…”

Section: Discussionmentioning

confidence: 99%

Matryoshka-Type Liposomes Offer the Improved Delivery of Temoporfin to Tumor Spheroids

Yakavets

Millard

Lamy

et al. 2019

Cancers

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The balance between the amount of drug delivered to tumor tissue and the homogeneity of its distribution is a challenge in the efficient delivery of photosensitizers (PSs) in photodynamic therapy (PDT) of cancer. To date, many efforts have been made using various nanomaterials to efficiently deliver temoporfin (mTHPC), one of the most potent photosensitizers. The present study aimed to develop double-loaded matryoshka-type hybrid nanoparticles encapsulating mTHPC/cyclodextrin inclusion complexes in mTHPC-loaded liposomes. This system was expected to improve the transport of mTHPC to target tissues and to strengthen its accumulation in the tumor tissue. Double-loaded hybrid nanoparticles (DL-DCL) were prepared, characterized, and tested in 2D and 3D in vitro models and in xenografted mice in vivo. Our studies indicated that DL-DCL provided deep penetration of mTHPC into the multicellular tumor spheroids via cyclodextrin nanoshuttles once the liposomes had been destabilized by serum proteins. Unexpectedly, we observed similar PDT efficiency in xenografted HT29 tumors for liposomal mTHPC formulation (Foslip®) and DL-DCL.

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Section: Discussionmentioning

confidence: 99%

Matryoshka-Type Liposomes Offer the Improved Delivery of Temoporfin to Tumor Spheroids

Yakavets

Millard

Lamy

et al. 2019

Cancers

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“…In all probability, mTHPC molecules partially redistribute between inclusion complexes and a liposomal bilayer. Actually, the localization of mTHPC in DCLs may be analyzed by spectroscopic techniques as a special case of equilibrium competitive binding [ 31 , 32 ].…”

Section: Resultsmentioning

confidence: 99%

“…Spectral characteristics of mTHPC/Me-β-CD inclusion complexes and Foslip ® were previously described and were used here only for comparative analysis [ 16 , 32 ]. To estimate the fraction of mTHPC bound to β-CDs, we used two different spectral techniques: conventional circular dichroism and spectroscopic based approach related to the shape of Soret band ( Figure 2 ) [ 31 , 32 ].…”

Section: Resultsmentioning

confidence: 99%

Temoporfin-in-Cyclodextrin-in-Liposome—A New Approach for Anticancer Drug Delivery: The Optimization of Composition

et al. 2018

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The main goal of this study was to use hybrid delivery system for effective transportation of temoporfin (meta-tetrakis(3-hydroxyphenyl)chlorin, mTHPC) to target tissue. We suggested to couple two independent delivery systems (liposomes and inclusion complexes) to achieve drug-in-cyclodextrin-in-liposome (DCL) nanoconstructs. We further optimized the composition of DCLs, aiming to alter in a more favorable way a distribution of temoporfin in tumor tissue. We have prepared DCLs with different compositions varying the concentration of mTHPC and the type of β-cyclodextrin (β-CD) derivatives (Hydroxypropyl-, Methyl- and Trimethyl-β-CD). DCLs were prepared by thin-hydration technique and mTHPC/β-CD complexes were added at hydration step. The size was about 135 nm with the surface charge of (−38 mV). We have demonstrated that DCLs are stable and almost all mTHPC is bound to β-CDs in the inner aqueous liposome core. Among all tested DCLs, trimethyl-β-CD-based DCL demonstrated a homogenous accumulation of mTHPC across tumor spheroid volume, thus supposing optimal mTHPC distribution.

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“…The encapsulation efficiency of mTHPC in MDCL and MDCL DL was 5% and 11 %. The presence of mTHPCin the soluble form of inclusion complexes was confirmed by spectroscopic techniques described previously 9,19,20 .…”

Section: Characterizationmentioning

confidence: 99%

“…To assess the structural stability of DCLs in human plasma, we used size-exclusion chromatography technique. Size-exclusion chromatography is the traditional method to analyze the affinity of the pharmaceutical compounds for serum proteins based on the separation of the serum into individual protein fractions according to their size 17,19 . The large-scale components don't pass to the gel beads, so they are excluded first, while small components pass through the gel beads and are excluded the last.…”

Section: Stability In Serummentioning

confidence: 99%

Cyclodextrin-based photoactive liposomal nanoparticles for tumor targeting

Yakavets

Lassalle

Zorin

et al. 2019

17th International Photodynamic Association World Congress

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The present study is aimed at the development of drug-in-cyclodextrin-in-liposome (DCL) nanoconstruct by coupling two independent delivery systems: cyclodextrin/mTHPC inclusion complexes and liposomal vesicles to improve the transport of mTHPC to the target tissue and to strengthen its intra-tissue accumulation in the tumor. Liposomes offer an excellent opportunity to achieve selective drug, targeting what is expected to prevent local irritation and reduce drug toxicity. Сyclodextrins (CDs) have been utilized as independent carriers for improvement of pharmaceutical properties such as solubility, stability, and bioavailability of various drug molecules, including mTHPC. Therefore, we assumed that encapsulation of CD-complexed drug into liposomes might increase drug loading capacity, entrapment efficiency, may restrain the dissociation of drug-CD complexes and prolong its systemic circulation.DCL nanoparticles have been prepared with various compositions to optimize the structure aiming to alter more favorably the distribution of temoporfin in tumor tissue. To enhance the encapsulation efficiency, double loaded DCLs, which include mTHPC in lipid bilayer along with (CD-mTHPC) inclusion complexes in the inner aqueous lumen, were prepared. It was demonstrated that DCLs possessed higher serum stability compared with conventional mTHPC liposomes (Foslip ® ). In fine, we showed that the presence of serum in the medium less affected cellular uptake of mTHPC delivered by double loaded MDCL compared with Foslip ® .

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Optical Methods for the Analysis of the Temoprofin Photosensitizer Distribution Between Serum Proteins and Methyl-β-Cyclodextrin Nanocarriers in Blood Serum

Cited by 7 publications

References 17 publications

Matryoshka-Type Liposomes Offer the Improved Delivery of Temoporfin to Tumor Spheroids

Matryoshka-Type Liposomes Offer the Improved Delivery of Temoporfin to Tumor Spheroids

Temoporfin-in-Cyclodextrin-in-Liposome—A New Approach for Anticancer Drug Delivery: The Optimization of Composition

Cyclodextrin-based photoactive liposomal nanoparticles for tumor targeting

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