Nano-Encapsulation of Mithramycin in Transfersomes and Polymeric Micelles for the Treatment of Sarcomas

Estupiñán, Óscar; Rendueles, Claudia; Suárez, Paula; Rey, Verónica; Murillo, Dzohara; Morís, Francisco; Gutiérrez, Gemma; Blanco‐López, M. Carmen; Matos, María

doi:10.3390/jcm10071358

Cited by 10 publications

(7 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Phosphatidylcholine and Tween 20 are classic transfersomal ingredients [ 26 , 27 , 28 , 29 , 30 ]. In addition to Tween 20, other non-ionic surfactants can also be included in the transfersome composition: sodium deoxycholate, sorbitan monooleate (Span 80), polysorbate 80 (Tween 80) [ 31 , 32 , 33 ], etc.…”

Section: Discussionmentioning

confidence: 99%

Transdermal Delivery of 2-PAM as a Tool to Increase the Effectiveness of Traditional Treatment of Organophosphate Poisoning

Васильева

Gaynanova

Zueva

et al. 2022

IJMS

View full text Add to dashboard Cite

For the first time, the efficacy of post-exposure treatment of organophosphate (OP) poisoning was increased by transdermal delivery of acetylcholinesterase (AChE) reactivator pyridine-2-aldoxime methochloride (2-PAM) as a preventive countermeasure. By selecting the optimal ratio of components, classical transfersomes (based on soybean phosphatidylcholine and Tween 20) and modified transfersomes (based on soybean phosphatidylcholine, Tween 20 and pyrrolidinium cationic surfactants with different hydrocarbon tail lengths) were obtained for 2-PAM encapsulation. Transfersomes modified with tetradecylpyrrolidinium bromide showed the best results in encapsulation efficiency and sustained release of 2-PAM from vesicles. Using Franz cells, it was found that the incorporation of surfactants into PC liposomes results in a more prolonged release of 2-PAM through the rat skin. Transfersomes containing 2-PAM, after exhaustive physical and chemical characterization, were embedded in a gel based on Carbopol® 940. A significantly high degree of erythrocyte AChE reactivation (23 ± 7%) was shown for 2-PAM in unmodified transfersomes in vivo. Preliminary transdermal administration of 2-PAM 24 h before emergency post-exposure treatment of OP poisoning leads to an increase in the survival rate of rats from 55% to 90%.

show abstract

Section: Discussionmentioning

confidence: 99%

Transdermal Delivery of 2-PAM as a Tool to Increase the Effectiveness of Traditional Treatment of Organophosphate Poisoning

Васильева

Gaynanova

Zueva

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…Cell viability of cell lines in the presence of increasing concentrations of different drugs was assayed using the cell proliferation reagent WST-1 (Roche, Mannheim, Germany) after 72 h-treatments as previously reported 35, 36 . IC 50 for each treatment was determined by non-linear regression using GraphPad Prism 9.0.1 software (Graphpad Software Inc., San Diego, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

A personalized medicine approach identifies enasidenib as an efficient treatment for IDH2 mutant chondrosarcoma

Rey,

Tornín,

Alba-Linares

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

BackgroundSarcomas represent an extensive group of malignant diseases affecting mesodermal tissues. Among sarcomas, the clinical management of chondrosarcomas remains a complex challenge, as high-grade tumors do not respond to current therapies. Mutations in theisocitrate dehydrogenase(IDH) 1 and 2 genes are among the most common mutations detected in chondrosarcomas and may represent a therapeutic opportunity. The presence of mutated IDH (mIDH) enzymes results in the accumulation of the oncometabolite 2-HG leading to molecular alterations that contribute to drive tumor growth.MethodsWe developed a personalized medicine strategy based on the targeted NGS/Sanger sequencing of sarcoma samples (n=6) and the use of matched patient-derived cell lines as a drug-testing platform. The anti-tumor potential of IDH mutations found in two chondrosarcoma cases was analyzed in vitro, in vivo and molecularly (transcriptomic and DNA methylation analyses).FindingsWe treated several chondrosarcoma models with specific mIDH1/2 inhibitors. Among these treatments, only the mIDH2 inhibitor enasidenib was able to decrease 2-HG levels and efficiently reduce the viability of mIDH2 chondrosarcoma cells. Importantly, oral administration of enasidenib in xenografted mice resulted in a complete abrogation of tumor growth. Enasidenib induced a profound remodeling of the transcriptomic landscape not associated to changes in the 5mC methylation levels and its anti-tumor effects were associated with the repression of proliferative pathways such as those controlled by E2F factors.InterpretationOverall, this work provides the first preclinical evidence for the use of enasidenib to treat mIDH2 chondrosarcomas.FundingSpanish Research Agency (grants PID2019-106666RB-I00; PI20CIII/00020; DTS18CIII/00005; CB16/12/00390; CB06/07/1009; CB19/07/00057).RESEARCH IN CONTEXTEvidence before this studySarcomas represent an extensive group of malignant diseases affecting mesodermal tissues. The genomic nature of most sarcoma subtypes, displaying high inter- and intra-tumor heterogeneity with few recurrent driver mutations in a small portion of patients, makes these tumors especially indicated for personalized treatment approaches. For optimal development of these personalized protocols and a more efficient translation to the clinic, it is necessary to create patient-derived models suitable for testing the efficiency of candidate therapies. These strategies might be especially indicated for chondrosarcomas, a subtype of bone sarcoma that is inherently resistant to current therapies.Added value of this studyTo develop a personalized medicine strategy for sarcomas we have applied targeted sequencing protocols to detect druggable mutations in a collection of sarcomas cases with available patient-derived models. Among those potential druggable alterations detected in patient samples and avatar cell lines, we found IDH mutations in two chondrosarcomas. The presence of mutated IDH enzymes results in the accumulation of the oncometabolite 2-HG which contributes to driving tumor growth. In vitro and in vivo experiments evidenced the anti-tumor potential of the IDH mutant inhibitor enasidenib for the treatment of IDH2 mutant chondrosarcomas. Our transcriptomic and epigenomic analyses show that the mechanism of action of this drug is associated with the repression of proliferative pathways rather than with the promotion of tumor differentiation.Implications of all the available evidenceThis study suggests that enasidenib may represent an efficient therapeutic alternative for mutant IDH2 chondrosarcomas. This anti-proliferative mechanism of action of this drug may be especially relevant in dedifferentiated chondrosarcomas where reversal of this phenotype is not possible. In addition, this work provides support for the use of sarcoma patient-derived lines as avatar models capable of predicting (pre)-clinical responses in personalized medicine strategies.

show abstract

“…As with free MTM, nanocarrier-delivered MTM also effectively suppressed SP1-mediated signaling. This suggests they may provide a safer delivery option for MTM that could be investigated for clinical use in the future ( EstupiñánRendueles et al, 2021 ).…”

Section: Plga Targeted Nano-drug Delivery Systemsmentioning

confidence: 99%

PLGA-based drug delivery systems in treating bone tumors

Qiu

Liu

2023

Front. Bioeng. Biotechnol.

View full text Add to dashboard Cite

Bone tumor has become a common disease that endangers human health. Surgical resection of bone tumors not only causes biomechanical defects of bone but also destroys the continuity and integrity of bone and cannot completely remove the local tumor cells. The remaining tumor cells in the lesion bring a hidden danger of local recurrence. To improve the chemotherapeutic effect and effectively clear tumor cells, traditional systemic chemotherapy often requires higher doses, and high doses of chemotherapeutic drugs inevitably cause a series of systemic toxic side effects, often intolerable to patients. PLGA-based drug delivery systems, such as nano delivery systems and scaffold-based local delivery systems, can help eliminate tumors and promote bone regeneration and therefore have more significant potential for application in bone tumor treatment. In this review, we summarize the research progress of PLGA nano drug delivery systems and PLGA scaffold-based local delivery systems in bone tumor treatment applications, expecting to provide a theoretical basis for developing novel bone tumor treatment strategies.

show abstract

Nano-Encapsulation of Mithramycin in Transfersomes and Polymeric Micelles for the Treatment of Sarcomas

Cited by 10 publications

References 65 publications

Transdermal Delivery of 2-PAM as a Tool to Increase the Effectiveness of Traditional Treatment of Organophosphate Poisoning

Transdermal Delivery of 2-PAM as a Tool to Increase the Effectiveness of Traditional Treatment of Organophosphate Poisoning

A personalized medicine approach identifies enasidenib as an efficient treatment for IDH2 mutant chondrosarcoma

PLGA-based drug delivery systems in treating bone tumors

Contact Info

Product

Resources

About