Design of a Multicompartment Hydrogel that Facilitates Time‐Resolved Delivery of Combination Therapy and Synergized Killing of Glioblastoma

Majumder, Poulami; Baxa, Ulrich; Walsh, Scott T. R.; Schneider, Joel P.

doi:10.1002/anie.201806483

Cited by 87 publications

(79 citation statements)

References 32 publications

(31 reference statements)

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“…Liposomal formulations designed according to this strategy have shown to be able to maintain drug ratios in the plasma after injection as well as deliver to the formulated drug ratio directly to the tumor tissue. This ensures that the effect observed in vitro is translated into in vivo, and chemotherapy is optimized [12,13,14,15,16,17,18]. Finally, the idea was validated in the clinics for a liposomal formulation co-encapsulating a fixed ratio of cytarabine:daunorubicin, approved by the Food and Drug Administration (FDA) in 2017, under the trademark of Vyxeos [19,20].…”

Section: Introductionmentioning

confidence: 99%

Short and Long-Term Effects of the Exposure of Breast Cancer Cell Lines to Different Ratios of Free or Co-Encapsulated Liposomal Paclitaxel and Doxorubicin

2019

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Background: Associating paclitaxel (PTX) to doxorubicin (DXR) is one of the main chemotherapy strategies for breast cancer (BC) management. Protocols currently available consist in administering both drugs on their maximum tolerated dose, not taking into account the possible differences in efficacy due to their combination ratio. In the present study, the short and long-term cytotoxic effects as well as migratory effects of PTX, DXR, and its combinations at 10:1; 1:1 and 1:10 PTX:DXR molar ratios either free or co-encapsulated in liposomes were evaluated against three human BC cell lines (MDA-MB-231, MCF-7, and SKBR-3). Method: The MTT assay was used to screen for synergy or antagonism between PTX and DXR and the combination index value was calculated using the CalcuSyn software. Nuclear morphological alterations were evaluated by staining the cells with Hoescht 33342. The investigation of senescence and clonogenicity of BC cell lines exposed to different treatments was also studied. In addition, the ability of these cells to migrate was assessed. Results: Taken together, the results presented herein allow us to suggest that there is no benefit in enhancing the PTX concentration above that of DXR in the combination for any of the three cell lines tested. Conclusion: The developed liposomes co-encapsulating PTX and DXR in different molar ratios retained the biological properties of the mixture of free drugs and are valuable for planning new therapeutic strategies.

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Section: Introductionmentioning

confidence: 99%

Short and Long-Term Effects of the Exposure of Breast Cancer Cell Lines to Different Ratios of Free or Co-Encapsulated Liposomal Paclitaxel and Doxorubicin

2019

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“…We confirmed that VCM-NPs can release slowly from the gel network and then release VCM, which is similar to results in a previous report. 46 , 48 Based on the release results and the degradation of the hydrogel, the mechanism of release from VCM-NPs/Gel is thought to be a combination of diffusion and erosion, which sustained the drug release. Therefore, the CS/β-GP/α-GP hydrogel is an ideal drug carrier for controlled drug release, and the hydrogel loaded with VCM-NPs shows significant potential for biomedical fields, including as materials for soft tissue defect repair and cell scaffolds.…”

Section: Resultsmentioning

confidence: 99%

<p>Injectable Chitosan-Based Thermosensitive Hydrogel/Nanoparticle-Loaded System for Local Delivery of Vancomycin in the Treatment of Osteomyelitis</p>

Jin¹,

Zhang²,

Shen³

et al. 2020

IJN

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Purpose: Osteomyelitis, particularly chronic osteomyelitis, remains a major challenge for orthopedic surgeons. The traditional treatment for osteomyelitis, which involves antibiotics and debridement, does not provide a complete solution for infection and bone repair. Antibiotics such as vancomycin (VCM) are commonly used to treat osteomyelitis in clinical settings. VCM use is limited by a lack of effective delivery methods that provide sustained, high doses to entirely fill irregular bone tissue to treat infections. Methods: We engineered a chitosan (CS)-based thermosensitive hydrogel to produce a VCM-nanoparticle (NPs)/Gel local drug delivery system. The VCM-NPs were formed with quaternary ammonium chitosan and carboxylated chitosan nanoparticles (VCM-NPs) by positive and negative charge adsorption to enhance the encapsulation efficiency and drug loading of VCM, with the aim of simultaneously preventing infection and repairing broken bones. This hydrogel was evaluated in a rabbit osteomyelitis model. Results: The VCM-NPs had high encapsulation efficiency and drug loading, with values of 60.1±2.1% and 24.1±0.84%, respectively. When embedded in CS-Gel, the VCM-NPs maintained their particle size and morphology, and the injectability and thermosensitivity of the hydrogel, which were evaluated by injectability test and rheological measurement, were retained. The VCM-NPs/Gel exhibited sustained release of VCM over 26 days. In vitro tests revealed that the VCM-NPs/Gel promoted osteoblast proliferation and activity against Staphylococcus aureus. In vivo, VCM-NPs/Gel (with 10 mg vancomycin per rabbit) was used to treat rabbits with osteomyelitis. The VCM-NPs/Gel showed excellent anti-infection properties and accelerating bone repair under osteomyelitis conditions. Conclusion: The reported multifunctional NPs hydrogel system for local antibiotic delivery (VCM-NPs/Gel) showed bone regeneration promotion and anti-infection properties, demonstrating significant potential as a scaffold for effective treatment of osteomyelitis.

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“…Delivering paclitaxel in the form of shortened filaments and/or potentially the reassembled spherical assemblies, as opposed to the monomeric individual drug conjugates, could lead to an enhanced distribution throughout the tumor intersitium with a better controlled drug release, as revealed by other groups. [29] Furthermore, drugs in the nanoparticle form could exhibit an enhanced cellular uptake and are also protected from rapid intracellular breakdown. [30] Nanoparticles could also help overcome multi-drug resistance.…”

Section: Cell-controlled Drug Releasementioning

confidence: 99%

Supramolecular Design of Unsymmetric Reverse Bolaamphiphiles for Cell‐Sensitive Hydrogel Degradation and Drug Release

Chakroun,

Sneider,

Anderson

et al. 2020

Angew Chem Int Ed

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Self‐assembly of peptide‐based building units into supramolecular nanostructures creates an important class of biomaterials with robust mechanical properties and improved resistance to premature degradation. Yet, upon aggregation, substrate–enzyme interactions are often compromised because of the limited access of macromolecular proteins to the peptide substrate, leading to either a reduction or loss of responsiveness to biomolecular cues. Reported here is the supramolecular design of unsymmetric reverse bolaamphiphiles (RBA) capable of exposing a matrix metalloproteinase (MMP) substrate on the surface of their filamentous assemblies. Upon addition of MMP‐2, these filaments rapidly break into fragments prior to reassembling into spherical micelles. Using 3D cell culture, it is shown that drug release is commensurate with cell density, revealing more effective cell killing when more cancer cells are present. This design platform could serve as a cell‐responsive therapeutic depot for local chemotherapy.

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Design of a Multicompartment Hydrogel that Facilitates Time‐Resolved Delivery of Combination Therapy and Synergized Killing of Glioblastoma

Cited by 87 publications

References 32 publications

Short and Long-Term Effects of the Exposure of Breast Cancer Cell Lines to Different Ratios of Free or Co-Encapsulated Liposomal Paclitaxel and Doxorubicin

Short and Long-Term Effects of the Exposure of Breast Cancer Cell Lines to Different Ratios of Free or Co-Encapsulated Liposomal Paclitaxel and Doxorubicin

<p>Injectable Chitosan-Based Thermosensitive Hydrogel/Nanoparticle-Loaded System for Local Delivery of Vancomycin in the Treatment of Osteomyelitis</p>

Supramolecular Design of Unsymmetric Reverse Bolaamphiphiles for Cell‐Sensitive Hydrogel Degradation and Drug Release

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