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- 저자 : Karim Md. Emranul (검색결과 3 건)
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Scope and challenges of nanoparticle-based mRNA delivery in cancer treatment
Md. Emranul Karim,Sheikh Tanzina Haque,Hamed Al-Busaidi,Athirah Bakhtiar,Kyi Kyi Tha,Mark M. Banaszak Holl,Ezharul Hoque Chowdhury 대한약학회 2022 Archives of Pharmacal Research Vol.45 No.12
Messenger RNA (mRNA) recently emerged asan appealing alternative to treat and prevent diseases rangingfrom cancer and Alzheimer’s disease to COVID-19 withsignifi cant clinical outputs. The in vitro-transcribed mRNAhas been engineered to mimic the structure of natural mRNAfor vaccination, cancer immunotherapy and protein replacementtherapy. In past decades, signifi cant progress has beennoticed in unveiling the molecular pathways of mRNA,controlling its translatability and stability, and its evolutionarydefense mechanism. However, numerous unsolvedstructural, biological, and technical diffi culties hamper thesuccessful implementation of systemic delivery of mRNAfor safer human consumption. Advances in designing and manufacturing mRNA and selecting innovative deliveryvehicles are mandatory to address the unresolved issuesand achieve the full potential of mRNA drugs. Despite thesubstantial eff orts made to improve the intracellular deliveryof mRNA drugs, challenges associated with diverse applicationsin diff erent routes still exist. This study examines thecurrent progress of mRNA therapeutics and advancementsin designing biomaterials and delivery strategies, the existingtranslational challenges of clinical tractability and theprospects of overcoming any challenges related to mRNA.
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Rehan Farah,Emranul Karim Md.,Ahemad Nafees,Farooq Shaikh Mohd.,Gupta Manish,Gan Siew Hua,Chowdhury Ezharul Hoque 한국약제학회 2022 Journal of Pharmaceutical Investigation Vol.52 No.6
Purpose Natural materials have been extensively studied for oral drug delivery due to their biodegradability and other unique properties. In the current research, we fabricated sodium caseinate nanomicelles (NaCNs) using casein as a natural polymer to develop a controlled-release oral delivery system that would improve the therapeutic potential of doxorubicin (DOX) and reduce its toxicity. Methods DOX-loaded NaCNs were synthesized and thoroughly characterized, then subjected to in vivo anti-tumor evaluation and bio-distribution analysis in a 4T1-induced breast cancer model. Results Our findings indicated that the tumor would shrink by eight-fold in the group orally treated with DOX-NaCNs when compared to free DOX. The tumor accumulated drug 1.27-fold more from the orally administered DOX-NaCNs compared to the intravenously administered DOX-NaCNs, 6.8-fold more compared to free DOX, and 8.34-times more compared to orally administered free DOX. In comparison, the orally administered DOX-NaCNs lead to a significant reduction in tumor size (5.66 ± 4.36 mm3) compared to intravenously administered DOX-NaCNs (10.29 ± 4.86 mm3) on day 17 of the experiment. NaCNs were well tolerated at a single dose of 2000 mg/kg in an acute oral toxicity study. Conclusion The enhanced anti-tumor effects of oral DOX-NaCNs might be related to the controlled release of DOX from the delivery system when compared to free DOX and the intravenous formulation of DOX-NaCNs. Moreover, NaCNs is recognized as a safe and non-toxic delivery system with excellent bio-distribution profile and high anti-tumor effects that has a potential for oral chemotherapy.
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Haque Sheikh Tanzina,Karim Md. Emranul,Othman Iekhsan,Chowdhury Ezharul Hoque 한국약제학회 2022 Journal of Pharmaceutical Investigation Vol.52 No.3
In this work, pH-sensitive alpha-ketoglutaric acid-modified Fe/Mg-carbonate apatite (α-KAM-Fe/Mg-CA) NPs were introduced and found to be capable of promoting the selective delivery of cancer-killing drug doxorubicin (DOX) in breast cancer cells, while simultaneously mitigating DOX toxicity on normal cells.As part of the characterization and evaluation of α-KAM-Fe/Mg-CA NPs to target breast cancer cells, a series of assessments were performed, which included size measurements, morphological analysis, FTIR, cytotoxicity assessment, hemolysis, drug binding, cellular uptake, and pH-responsive drug release tests. Liquid chromatography-mass spectrometry was used to conduct the protein corona analysis of α-KAM-Fe/Mg-CA using 10% FBS (fetal bovine serum) and mice plasma. Furthermore, to investigate the distribution of DOX-loaded α-KAM-Fe/Mg-CA NPs in major tissues and the tumor, a biodistribution investigation was conducted in mammary tumor-induced Balb/c mouse models 24 h after the intravenous administration of DOX-loaded α-KAM-Fe/Mg-CA NPs.The in vitro pH-dependent release of DOX over time demonstrated that α-KAM-Fe/Mg-CA NPs were pH-responsive and degraded rapidly at acidic pH levels. When compared to free DOX, the DOX-loaded α-KAM-Fe/Mg-CA NPs demonstrated a potent antiproliferative effect on breast cancer cells. Confocal microscopy confirmed the effective internalization of DOX-loaded α-KAM-Fe/Mg-CA NPs in breast cancer cells. The protein corona analysis revealed an affinity for dysopsonins (serum albumin, apolipoproteins) and transport proteins that may assist in extending their blood circulation period. Furthermore, biodistribution data of DOX-loaded α-KAM-Fe/Mg-CA NPs in the mammary tumor-induced Balb/c mouse model indicated extended circulation in the bloodstream, reduced non-target distribution in major tissues, and increased drug accumulation in the tumor.The results obtained suggest that α-KAM-Fe/Mg-CA NPs may emerge as a prospective candidate for delivering therapeutic cargos to treat malignant mammary tumors.
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