Irinotecan (IRT) is an important part of the first- and second-line regimen for metastatic colorectal and some other cancers. However, IRT suffers the constraints of pH-dependent conversion of active lactone form to inactive carboxylate form, burst release owing to its aqueous solubility, short half-life and dose-dependent side effects. In this study, we developed polymeric nanoparticles (NPs) that not only deliver IRT to tumor sites, but also overcome its drawbacks by preserving active lactone conformation, prolonging the plasma circulation time, and by providing sustained release. IRT complex was rendered hydrophobic by ion-pairing with anions (docusate sodium, sodium lauryl sulfate, and sodium tripolyphosphate), and loaded in PEG-PLGA NPs via water/oil/water double emulsification method. The NPs were spherical, ∼60nm, monodispersed, and had shell-core morphology. They retained >80% lactone form for more than 1 month of storage and exhibited sustained release characteristics. In addition, sub -100nm size of NPs offered elevated cellular internalization. Owing to the presence of hydrophilic PEG outer layer and drug-loaded hydrophobic PLGA core, NPs conferred excellent plasma stability and prolonged the retention time of IRT by more than 10-fold as compared to free IRT. Therefore, this system could provide an excellent platform for efficient and sustained delivery of IRT and similar labile drugs to the tumor site, while maintaining their chemical integrity.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ijpharm.2016.08.018 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The Protein Engineering of Zearalenone Hydrolase Results in a Shift in the pH Optimum of the Relative Activity of the Enzyme.
Toxins (Basel)
December 2024
All-Russian Research Institute of Phytopathology of RAS, Bolshie Vyazemy, 143050 Moscow, Russia.
An acidic shift in the pH profile of zearalenone hydrolase (ZHD), the most effective and well-studied zearalenone-specific lactone hydrolase, is required to extend the range of applications for the enzyme as a decontamination agent in the feed and food production industries. Amino acid substitutions were engineered in the active center of the enzyme to decrease the pKa values of the catalytic residues E126 and H242. The T216K substitution provided a shift in the pH optimum by one unit to the acidic region, accompanied by a notable expansion in the pH profile under acidic conditions.
View Article and Find Full Text PDFExploring Mycolactone-The Unique Causative Toxin of Buruli Ulcer: Biosynthetic, Synthetic Pathways, Biomarker for Diagnosis, and Therapeutic Potential.
Toxins (Basel)
December 2024
Department of Chemistry, University of Ghana, Legon-Accra P.O. Box LG56, Ghana.
Mycolactone is a complex macrolide toxin produced by , the causative agent of Buruli ulcer. The aim of this paper is to review the chemistry, biosynthetic, and synthetic pathways of mycolactone A/B to help develop an understanding of the mode of action of these polyketides as well as their therapeutic potential. The synthetic work has largely been driven by the desire to afford researchers enough (≥100 mg) of the pure toxins for systematic biological studies toward understanding their very high biological activities.
View Article and Find Full Text PDFButyrolactone-I from Marine Fungal Metabolites Mitigates Heat-Stress-Induced Apoptosis in IPEC-J2 Cells and Mice Through the ROS/PERK/CHOP Signaling Pathway.
Mar Drugs
December 2024
Marine Medical Research and Development Centre, Shenzhen Institute of Guangdong Ocean University, Shenzhen 518120, China.
Heat stress poses a significant challenge to animal husbandry, contributing to oxidative stress, intestinal mucosal injury, and apoptosis, which severely impact animal health, growth, and production efficiency. The development of safe, sustainable, and naturally derived solutions to mitigate these effects is critical for advancing sustainable agricultural practices. Butyrolactone-I (BTL-I), a bioactive compound derived from deep-sea fungi (Aspergillus), shows promise as a functional feed additive to combat heat stress in animals.
View Article and Find Full Text PDFComposition of Triterpene Glycosides of the Far Eastern Sea Cucumber Levin et Stepanov; Structure Elucidation of Five Minor Conicospermiumosides A-1, A-2, A-3, A-1, and A-2; Cytotoxicity of the Glycosides Against Human Breast Cancer Cell Lines; Structure-Activity Relationships.
Mar Drugs
December 2024
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, Pr. 100-letya Vladivostoka 159, 690022 Vladivostok, Russia.
Five new non-holostane di- and trisulfated triterpene pentaosides, conicospermiumosides A-1 (), A-2 (), A-3 (), A-1 (), and A-2 () were isolated from the Far Eastern sea cucumber Levin et Stepanov (Cucumariidae, Dendrochirotida). Twelve known glycosides found earlier in other species were also obtained and identified. The structures of new compounds were established on the basis of extensive analysis of the 1D and 2D NMR spectra, as well as by the HR-ESI-MS data.
View Article and Find Full Text PDFThree New Dipeptide and Two New Polyketide Derivatives from the Mangrove-Derived Fungus sp.: Antioxidant Activity of Two Isolated Substances.
Mar Drugs
December 2024
CAS Key Laboratory of Tropical Marine Bio-resources and Ecology/Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China.
Five new metabolites, including three cyclic dipeptide derivatives (-) and two new polyketides (-), together with nine known ones (- and -), were isolated from the mangrove-sediments-derived fungus sp. SCSIO 41431. Their structures were determined using detailed NMR, MS spectroscopic analyses, and quantum chemical calculations.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!