Wednesday, August 12, 2020

PEG-PLGA from PolySciTech used in development of daunorubicin nanoparticles for skin-cancer treatment

 

Treatment of cancer is complicated by lack of specificity for chemotherapeutic compounds against cancer leading to most of the promising drugs having side-effects that limit their usage. Combining chemotherapy with phototherapy, however, could provide for an improved combination treatment in which the two strategies are applied together. Recently, researchers at Warsaw University of Technology and Wrocław University of Science and Technology (Poland) used mPEG-PLGA (AK002) from PolySciTech (www.polyscitech.com) to create nanoparticles loaded with photosensitizer, IR-768, and chemotherapy agent, daunorubicin. This research holds promise to provide for improved therapies against cancer. Read more: Tokarska, Katarzyna, Łukasz Lamch, Beata Piechota, Kamil Żukowski, Michał Chudy, Kazimiera A. Wilk, and Zbigniew Brzózka. "Co-delivery of IR-768 and daunorubicin using mPEG-b-PLGA micelles for synergistic enhancement of combination therapy of melanoma." Journal of Photochemistry and Photobiology B: Biology (2020): 111981. https://www.sciencedirect.com/science/article/pii/S1011134420304310

“Malignant melanoma is an emerging problem worldwide due to the high degree of lethalness. Its aggressiveness and the ability to metastasize along with the heterogeneity at the molecular and cellular levels, limit the overall therapeutic efficacy. Despite significant advances in melanoma treatment over the last decade, there is still a need for improved therapeutic modalities. Thus, we demonstrate here a combinatorial approach that targets multiple independent therapeutic pathways, in which polymeric micelles (PMs) were used as efficacious colloidal nanocarriers loaded with both daunorubicin (DRB) as a cytotoxic drug and IR-768 as a photosensitizer. This afforded the dual drug loaded delivery system IR-768 + DRB in PMs. The fabricated mPEG-b-PLGA micelles (hydrodynamic diameters ≈ 25 nm) had a relatively narrow size distribution (PdI > ca. 0.3) with uniform spherical shapes. CLSM study showed that mPEG-b-PLGA micelles were uptaken by mitochondria, which further contributed to excellent singlet oxygen generation capacity for PDT in A375 melanoma cells. Furthermore, the PMs were efficiently internalized by tested cells through endocytosis, resulting in much higher cellular uptake comparing to the free drug. As a result of these properties, IR-768 + DRB in PMs exhibited very potent and synergistically enhanced anticancer activity against A375 cells. Additionally, this combination approach allowed to reduce drug doses and provided low side effects towards normal HaCaT. This study indicates excellent properties of mPEG-b-PLGA micelles resulting in great therapeutic potential possessed by the developed nanoscale drug delivery system for combined chemo-photodynamic therapy of melanoma. Keywords: Co-encapsulation Polymeric micelles Combination therapy Photodynamic therapy Melanoma Nanoscale drug delivery systems”

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