ABSTRACT
This study focuses on the design and evaluation of redox-responsive nanoparticles (NPs) by synthesizing disulfide-containing N-phthaloyl chitosan-SS-methoxy poly(ethylene glycol) (NPC-SS-mPEG) and incorporating the anti-cancer drug doxorubicin into the NPs. The structural features of NPC-SS-mPEG were investigated using FTIR, NMR, XRD, and TGA/DTA analysis. DLS and TEM analysis confirmed the particle size and morphology of the NPs. The stability of the NPs was measured with the presence and absence of glutathione (GSH) in buffers pH 5 and 7.4. Furthermore, the release of DOX from the NPs was studied in GSH (10 mM) containing/absent medium at pH 5 and pH 7.4 which mimics the intracellular environment with redox potential. The results indicated a significantly increased release of DOX in the GSH containing medium pH 5 (82.9 ± 2.1 %) and pH 7.4 (67.37 ± 0.88 %) compared to the GSH free pH 7.4 (29.99 ± 1.01 %) and pH 5 medium (56.56 ± 1.7 %) at 60 h. The cytotoxicity study in the MDA-MB-231 breast cancer cell line by MTT assay indicated higher toxicity of redox-responsive NPs to cancer cells than free DOX. In concurrence with the cytotoxicity assay, in-vitro fluorescence staining assays (AO/EB, Hoechst, ROS generation) also confirmed that NPs loaded with DOX induce higher toxicity to cancer cells than free DOX. Taken together, the overall results confirmed the superiority of the redox response-mediated release of DOX in effectively controlling cancer progression.
Subject(s)
Chitosan , Nanoparticles , Humans , Doxorubicin/pharmacology , Doxorubicin/chemistry , Chitosan/pharmacology , Chitosan/chemistry , MDA-MB-231 Cells , Polyethylene Glycols/chemistry , Oxidation-Reduction , Nanoparticles/chemistry , Hydrogen-Ion Concentration , Drug Carriers/chemistry , Drug Delivery Systems/methodsABSTRACT
Vibrating mesh nebulizers are recognized as the most efficient actuation technique over conventional inhalers for drug deposition. This study explored hyaluronic acid (HA) decorated, ferulic acid (FA) loaded chitosan (CS) nanoparticle (FACHA) aerosolized using vibrating mesh nebulizer as strategic combination of drug, nanocarrier and delivery device for effective asthma control. FACHA exhibited spherical morphology with suitable size (164.2 ± 9.7 nm), zeta potential (24.0 ± 0.5 mV), entrapment efficiency (EE%) (65.0 ± 1.5), loading capacity (LC%) (18.5 ± 0.4) and mass median aerodynamic diameter (MMAD) of 1.81 ± 0.15 µm, ascertaining efficient drug deposition. In vivo inhalation toxicity assessment confirmed safety, while, FACHA prophylaxis mitigated inflammation, airway hypersensitivity and remodelling in ovalbumin (OVA) induced mice models. The results thus accentuated the role of pro-pulmonary surface chemistry conferred by HA functionalization that improved 1) thermal stability (thermogravimetric analysis - TGA) and 2) therapeutic efficacy of FA, by facilitating better interaction and transportation across mucus barrier, which otherwise suffers poor bioavailability and rapid metabolism.
Subject(s)
Asthma , Chitosan , Nanoparticles , Animals , Asthma/drug therapy , Coumaric Acids , Hyaluronic Acid , Mice , Particle SizeABSTRACT
BACKGROUND: The leaves of Ziziphus mauritiana Lam have been an integral part of the traditional system of medicine for the treatment of inflammation, wounds, fever, asthma and liver disorders. The leaves are utilised as an edible vegetable in rural parts of India and Indonesia. Despite its pharmacological significance, Ziziphus mauritiana Lam lacks scientific evidence on its mutagenic and genotoxic potential. RATIONALE: The aim of the present work is to identify bioactive compounds present in the methanol extract of Ziziphus mauritiana Lam leaves (MEZ) using HPLC-ESI-QqQ and to evaluate its mutagenic and genotoxic potential. METHODS: The phytochemical standardization of the MEZ was done using HPLC-ESI-QqQ. The mutagenic and genotoxic potential of MEZ was tested using bacterial reverse mutation (Ames test), chromosomal aberration, and micronucleus tests. The Ames test was performed in Salmonella typhimurium strains TA98, TA100, TA102, TA1535 and TA1537, and the genotoxic potential was tested in in-vitro using chromosome aberration assay with Chinese hamster ovary (CHO) cells and in-vivo micronucleus test using mouse bone marrow cells. RESULTS: Fifteen phytochemical compounds were identified in HPLC-ESI- QqQ. It was observed from the Ames test that MEZ did not induce gene mutations in the S. typhimurium in the presence or absence of S9 activation. Similarly, no significant increase in the number of structural aberrations was observed in CHO cells with or without S9 activation. The oral administration of MEZ at a dose of up to 2000â¯mg/kg caused no significant increase in the number of micronucleated polychromatic erythrocytes or in the mean ratio of polychromatic to total erythrocytes. CONCLUSION: The findings of the present study confirm that MEZ is not-mutagenic and non-genotoxic in the presence or absence of the exogenous metabolizing system.