Current Drug Delivery - Online First
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Alleviation of Tumor Invasion by the Development of Natural Polymer-based Low-risk Chemotherapeutic Systems – review on the Malignant Carcinoma Treatments
Available online: 14 October 2024More LessIntroduction/ObjectiveThe spread of tumors (48% in men and 51% in women), as well as the protection of malignant tumors by stromal cells and complex blood vessels, pose significant challenges to drug delivery to tumors. Modern chemotherapy, on the other hand, addresses tumor growth suppression by at least 60% through versatile formulation systems and numerous modifications to drug delivery systems. The renewable and naturally occurring polymers present invariably in all living cells form the fundamental foundation for most anticancer drug development. The review aims to discuss in detail the preparations of polysaccharide, lipid, and protein-based drug-loading vehicles for the targeted delivery of prominent anticancer drugs. It also provides an explanation of drug distribution in blood (cumulative releases of nearly 80% drug) and drug accumulation at tumor sites (1–5 mg/kg) due to enhanced permeability and retention (EPR).
MethodsSpecific delivery examples for treating colorectal and breast carcinomas have been presented to distinguish the varied drug administration, bioavailability, and tumor internalization mechanisms between sugar, fatty acid, and amino acid polymers. Current therapy possibilities based on cutting-edge literature are provided, along with drug delivery systems tailored to tumor location and invasive properties.
ResultsThe unique combinations of the three natural polymers provide unparalleled solutions to minimize the toxicity (<20% drug release) of the chemotherapeutic drugs on normal tissues. Moreover, the development of a consolidated drug delivery system has contributed to a substantial reduction (dose reduction from 10.43 µM to 1.9 µM) in the undesirable consequences of higher dosages of chemotherapeutic drugs.
ConclusionThe review extensively covers safe chemotherapeutic systems with significant advantages (tumor volume shrinkage of 4T1 cells from 1000 mm3 to 200 mm3) in clinical applications of carcinoma treatments using natural polymers.
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Nanoparticle-Mediated Transcytosis in Tumor Drug Delivery: Mechanisms, Categories, and Novel Applications
Authors: Nakaooh Doaa, Signa Lon Rolande Detorgma, Kaiyun Yang, Rajae Salama and Wenli ZhangAvailable online: 10 October 2024More LessThe development of nanotechnology-based drug delivery systems has been extensively investigated across various therapies, leading to the creation of numerous nanomedicines for clinical use. However, these nanomedicines have yet to achieve the anticipated therapeutic efficacy in clinical settings, highlighting the urgent need for further research in this area. A primary challenge in nanomedicine research lies in ensuring that nanoparticles and therapeutic agents can effectively penetrate and accumulate within tumors. The enhanced permeability and retention (EPR) effect has been previously explored as a means to enhance drug delivery to tumors, but recent findings have revealed its limitations, including variable responses, restricted penetration, clearance by the reticuloendothelial system, and non-specific accumulation. As an alternative approach, transcytosis has been explored for delivering drugs to specific organs or tissues, potentially bypassing some of the constraints of the EPR effect. For example, nanoparticles can be guided through barriers by targeting specific receptors on cell surfaces or by utilizing a different charge compared to tumor cells' surfaces. Therefore, this article explores transcytosis, including adsorptive, receptor-mediated, and cell-mediated subtypes, all of which have demonstrated promising results and offer potential solutions to enhance the effectiveness of nanomedicine delivery for cancer therapy.
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Multi-Stimuli-Responsive Biocompatible Magnetic Nanocarrier as Drug Delivery System to MCF-7 Breast Cancer Cells
Available online: 04 October 2024More LessIntroductionThe last strategy in targeted drug delivery systems is to deliver the anticancer drug to the tumor tissue to increase its therapeutic effect and minimize its undesirable side effects. In line with this goal in this research, the redox/pH-responsive disulfide magnetic nanocarriers based on PF127-NH2/L-cysteine-CM-β-CD-FA were synthesized and evaluated in a doxorubicin delivery system.
MethodsWe effectively surrounded Fe3O4 nanoparticles with SiO2 using the sol-gel method, and then confidently coated them with oleic acid on Fe3O4@SiO2 nanoparticles.. In another reaction, a PF127-NH2/L-cysteine-CM-β-CD-FA was synthesized. The process involved modifying pluronic F127 (PF 127) with maleic anhydride and aminating it to form PF127-NH2. The obtained PF127-NH2 was attached to L-cysteine, followed by condensing with carboxymethyl-β-cyclodextrin and then functionalized by folic acid. Finally, PF127-NH2/L-cysteine-CM-β-CD-FA was coated on the surface of magnetic nanoparticles, and the resulting PF127-NH2/L-cysteine-CM-β-CD-FA was disulfidated to form the final nanocarrier network, which was abbreviated as LCMNPs-SS. The doxorubicin was used as a model drug and loaded into the LCMNPs-SS nanocarrier.
ResultsThe LCMNPs-SS nanocarrier exhibited excellent properties for controlled release, with a well-defined release rate, a controllable level by an external magnet, and adjusting by DL-dithiothreitol concentration. The LCMNPs-SS nanocarrier could also break apart when exposed to an oxidant or a change in pH. This meant that the drug release could be fine-tuned in response to temperature, pH, or more than one stimulus.
ConclusionThese drug-carrying systems are valuable in reducing the dose of doxorubicin. High internalization of the synthesized LCMNPs-SS caused sped cellular uptake.
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Preface
Authors: Deng-Guang Yu and He Lv
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