Multidrug PLA-PEG filomicelles for concurrent delivery of anticancer drugs—The influence of drug-drug and drug-polymer interactions on drug loading and release properties

Jelonek, Katarzyna; Li, Suming; Kaczmarczyk, Bożena; Marcinkowski, Andrzej; Orchel, Arkadiusz; Musiał‐Kulik, Monika; Kasperczyk, Janusz

doi:10.1016/j.ijpharm.2016.06.051

Cited by 36 publications

(28 citation statements)

References 35 publications

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“…17-AAG content into inclusion complexes was estimated by dissolving a fixed amount of the complexes in methanol. Appropriate dilutions were made, and the 17-AAG content was calculated from UV absorbance recorded at λ max 333 nm, wavelength previously used to detect 17-AAG in polymer micelles (Jelonek et al, 2016 ). As described in Material and Methods section, 17-AAG concentration into liposomes was also determined using the ultrafiltration-centrifugation technique using Ultrafree ®; units.…”

Section: Discussionmentioning

confidence: 99%

Encapsulation of the HSP-90 Chaperone Inhibitor 17-AAG in Stable Liposome Allow Increasing the Therapeutic Index as Assessed, in vitro, on Leishmania (L) amazonensis Amastigotes-Hosted in Mouse CBA Macrophages

Petersen

Campos

Dantas

et al. 2018

Front. Cell. Infect. Microbiol.

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The current long-term treatment for leishmaniasis causes severe side effects and resistance in some cases. An evaluation of the anti-leishmanial potential of an HSP90-inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG), demonstrated its potent effect against Leishmania spp. in vitro and in vivo. We have previously shown that 17-AAG can kill L. (L) amazonensis promastigotes with an IC50 of 65 nM and intracellular amastigote at concentrations as low as 125 nM. As this compound presents low solubility and high toxicity in human clinical trials, we prepared an inclusion complex containing hydroxypropyl-β-cyclodextrin and 17-AAG (17-AAG:HPβCD) to improve its solubility. This complex was characterized by scanning electron microscopy, and X-ray diffraction. Liposomes-containing 17-AAG:HPβCD was prepared and evaluated for encapsulation efficiency (EE%), particle size, polydispersity index (PDI), pH, and zeta potential, before and after accelerated and long-term stability testing. An evaluation of leishmanicidal activity against promastigotes and intracellular amastigotes of L. (L) amazonensis was also performed. The characterization techniques utilized confirmed the formation of the inclusion complex, HPβCD:17-AAG, with a resulting 33-fold-enhancement in compound water solubility. Stability studies revealed that 17-AAG:HPβCD-loaded liposomes were smaller than 200 nm, with 99% EE. Stability testing detected no alterations in PDI that was 0.295, pH 7.63, and zeta potential +22.6, suggesting liposome stability, and suitability for evaluating leishmanicidal activity. Treatment of infected macrophages with 0.006 nM of 17-AAG:HPβCD or 17-AAG:HPβCD-loaded liposomes resulted in almost complete amastigote clearance inside macrophages after 48 h. This reduction is similar to the one observed in infected macrophages treated with 2 μM amphotericin B. Our results showed that nanotechnology and drug delivery systems could be used to increase the antileishmanial efficacy and potency of 17-AAG in vitro, while also resulting in reduced toxicity that indicates these formulations may represent a potential therapeutic strategy against leishmaniasis.

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Section: Discussionmentioning

confidence: 99%

Encapsulation of the HSP-90 Chaperone Inhibitor 17-AAG in Stable Liposome Allow Increasing the Therapeutic Index as Assessed, in vitro, on Leishmania (L) amazonensis Amastigotes-Hosted in Mouse CBA Macrophages

Petersen

Campos

Dantas

et al. 2018

Front. Cell. Infect. Microbiol.

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“…Many studies revealed prolonged release of all drugs in spite of an initial burst. Similarly, in the case of our PTX‐loaded micelles, PTX exhibits a burst release in the first 24 h ( Figure b), followed by a slower release (Figure a).…”

Section: Resultsmentioning

confidence: 99%

PLLA‐Grafted Gelatin Amphiphilic Copolymer and Its Self‐Assembled Nano Carrier for Anticancer Drug Delivery

Fan

et al. 2019

Macro Chemistry & Physics

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A series of poly(l‐lactide)‐grafted gelatin (Gel‐g‐PLLA) copolymers are synthesized by coupling the amino groups of gelatin with different molar masses and the carboxyl endgroup of poly(l‐lactide) in the presence of 1‐ethyl‐3‐(3‐dimethylaminopropyl)carbodiimide hydrochloride and N‐hydroxysuccinimide. Fourier transform infrared and nuclear magnetic resonance (1H NMR) data confirm the successful bonding between gelatin and PLLA. Self‐assembled micelles of copolymers are prepared by using the direct dissolution method. The size and micellar morphology are determined from dynamic light scattering as well as transmission electron microscopy measurements. Meanwhile, in vitro drug release reveals that Gel‐g‐PLLA micelles show excellent sustained‐release properties when used as the carrier of the anticancer drug paclitaxel. A burst release of about 70% is observed in the first 24 h. All these features, together with the outstanding biocompatibility, make Gel‐g‐PLLA micelles a promising drug carrier for cancer therapy.

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“…Two series of experimental tests of poly(lactic-co-glycolic acid) (PLGA) and PLLA blend bioresorbable polymers were performed to quantify the mechanical response of the material. The considered material was originally developed at the Centre of Polymer and Carbon Materials (CPCM) of the Institute of the Polish Academy of Sciences [25,26]. It is a copolymer of lactic acid and glycolic acid (the chemical formula is presented in Figure 1, while the basic physical-chemical properties, based on data provided by CPCM, are presented in Table 1) [27].…”

Section: Experimental Tests Of the Plga Bioresorbable Polymermentioning

confidence: 99%

Experimental Tests, FEM Constitutive Modeling and Validation of PLGA Bioresorbable Polymer for Stent Applications

et al. 2020

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The use of bioresorbable polymers such as poly(lactic-co-glycolic acid) (PLGA) in coronary stents can hypothetically reduce the risk of complications (e.g., restenosis, thrombosis) after percutaneous coronary intervention. However, there is a need for a constitutive modeling strategy that combines the simplicity of implementation with strain rate dependency. Here, a constitutive modeling methodology for PLGA comprising numerical simulation using a finite element method is presented. First, the methodology and results of PLGA experimental tests are presented, with a focus on tension tests of tubular-type specimens with different strain rates. Subsequently, the constitutive modeling methodology is proposed and described. Material model constants are determined based on the results of the experimental tests. Finally, the developed methodology is validated by experimental and numerical comparisons of stent free compression tests with various compression speeds. The validation results show acceptable correlation in terms of both quality and quantity. The proposed and validated constitutive modeling approach for the bioresorbable polymer provides a useful tool for the design and evaluation of bioresorbable stents.

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Multidrug PLA-PEG filomicelles for concurrent delivery of anticancer drugs—The influence of drug-drug and drug-polymer interactions on drug loading and release properties

Cited by 36 publications

References 35 publications

Encapsulation of the HSP-90 Chaperone Inhibitor 17-AAG in Stable Liposome Allow Increasing the Therapeutic Index as Assessed, in vitro, on Leishmania (L) amazonensis Amastigotes-Hosted in Mouse CBA Macrophages

Encapsulation of the HSP-90 Chaperone Inhibitor 17-AAG in Stable Liposome Allow Increasing the Therapeutic Index as Assessed, in vitro, on Leishmania (L) amazonensis Amastigotes-Hosted in Mouse CBA Macrophages

PLLA‐Grafted Gelatin Amphiphilic Copolymer and Its Self‐Assembled Nano Carrier for Anticancer Drug Delivery

Experimental Tests, FEM Constitutive Modeling and Validation of PLGA Bioresorbable Polymer for Stent Applications

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