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Magnetic cellulose nanocrystal stabilized Pickering emulsions for enhanced bioactive release and human colon cancer therapy

Low LE, Tan LT, Goh BH, Tey BT, Ong BH, Tang SY

Int J Biol Macromol, 2019 Apr 15;127:76-84.
PMID: 30639596 DOI: 10.1016/j.ijbiomac.2019.01.037

Stimuli-responsive drug release and controlled delivery play crucial roles in enhancing the therapeutic efficacy and lowering over-dosage induced side effects. In this paper, we report magnetically-triggered drug release and in-vitro anti-colon cancer efficacy of Fe3O4@cellulose nanocrystal (MCNC)-stabilized Pickering emulsions containing curcumin (CUR). The loading efficiency of CUR in the micron-sized (≈7 μm) MCNC-stabilized Pickering emulsions (MCNC-PE) template was found to be 99.35%. The drug release profiles showed that the exposure of MCNC-PE to external magnetic field (EMF) (0.7 T) stimulated the release of bioactive from MCNC-PE achieving 53.30 ± 5.08% of the initial loading over a 4-day period. The MTT assay demonstrated that the CUR-loaded MCNC-PE can effectively inhibits the human colon cancer cells growth down to 18% in the presence of EMF. The formulation also resulted in 2-fold reduction on the volume of the 3-D multicellular spheroids of HCT116 as compared to the control sample. The MCNC particle was found to be non-toxic to brine shrimp up to a concentration of 100 μg/mL. Our findings suggested that the palm-based MCNC-PE could be a promising yet effective colloidal drug delivery system for magnetic-triggered release of bioactive and therapeutics.

Matched MeSH terms: Delayed-Action Preparations/pharmacology
Fulltext ECM Mimicking Biodegradable Nanofibrous Scaffold Enriched with Curcumin/ZnO to Accelerate Diabetic Wound Healing via Multifunctional Bioactivity

Yadav S, Arya DK, Pandey P, Anand S, Gautam AK, Ranjan S, et al.

Int J Nanomedicine, 2022;17:6843-6859.
PMID: 36605559 DOI: 10.2147/IJN.S388264

INTRODUCTION: Foot ulceration is one of the most severe and debilitating complications of diabetes, which leads to the cause of non-traumatic lower-extremity amputation in 15-24% of affected individuals. The healing of diabetic foot (DF) is a significant therapeutic problem due to complications from the multifactorial healing process. Electrospun nanofibrous scaffold loaded with various wound dressing materials has excellent wound healing properties due to its multifunctional action.
PURPOSE: This work aimed to develop and characterize chitosan (CS)-polyvinyl alcohol (PVA) blended electrospun multifunctional nanofiber loaded with curcumin (CUR) and zinc oxide (ZnO) to accelerate diabetic wound healing in STZ-induced diabetic rats.
RESULTS: In-vitro characterization results revealed that nanofiber was fabricated successfully using the electrospinning technique. SEM results confirmed the smooth surface with web-like fiber nanostructure diameter ranging from 200 - 250 nm. An in-vitro release study confirmed the sustained release of CUR and ZnO for a prolonged time. In-vitro cell-line studies demonstrated significantly low cytotoxicity of nanofiber in HaCaT cells. Anti-bacterial studies demonstrated good anti-bacterial and anti-biofilm activities of nanofiber. In-vivo animal studies demonstrated an excellent wound-healing efficiency of the nanofibers in STZ-induced diabetic rats. Furthermore, the ELISA assay revealed that the optimized nanofiber membrane terminated the inflammatory phases successfully by downregulating the pro-inflammatory cytokines (TNF-α, MMP-2, and MMP-9) in wound healing. In-vitro and in-vivo studies conclude that the developed nanofiber loaded with bioactive material can promote diabetic wound healing efficiently via multifunction action such as the sustained release of bioactive molecules for a prolonged time of duration, proving anti-bacterial/anti-biofilm properties and acceleration of cell migration and proliferation process during the wound healing.
DISCUSSION: CUR-ZnO electrospun nanofibers could be a promising drug delivery platform with the potential to be scaled up to treat diabetic foot ulcers effectively.

Matched MeSH terms: Delayed-Action Preparations/pharmacology
Nanoparticle-laden contact lens for controlled release of vancomycin with enhanced antibiotic efficacy

Tong WY, Tan WN, Kamarul Azizi MA, Leong CR, El Azab IH, Lim JW, et al.

Chemosphere, 2023 Oct;338:139492.
PMID: 37451643 DOI: 10.1016/j.chemosphere.2023.139492

Vancomycin is the last resort antibiotic for the treatment of severe bacterial keratitis. Its clinical application is limited due to its hydrophilicity and high molecular weight. To overcome this, this study aims to develop nanoparticles-laden contact lens for controlled ocular delivery of vancomycin. Polyvinyl alcohol (PVA) was used as encapsulant material. The nanoparticles had a negative surface charge and an average size of 147.6 nm. A satisfactory encapsulation efficiency (61.24%) was obtained. The release profile was observed to be slow and sustained, with a release rate of 1.29 μL mg-1 h-1 for 48 h. Five out of 6 test bacteria were suppressed by vancomycin nanoparticles-laden contact lens. Vancomycin is generally ineffective against Gram-negative bacteria and unable to pass through the outer membrane barrier. In this study, vancomycin inhibited Proteus mirabilis and Pseudomonas aeruginosa. Nano-encapsulation enables vancomycin to penetrate the Gram-negative cell wall and further destroy the bacterial cells. On Hohenstein challenge test, all test bacteria exhibited significant reduction in growth when exposed to vancomycin nanoparticles-laden contact lens. This study created an effective and long-lasting vancomycin delivery system via silicone hydrogel contact lenses, by using PVA as encapsulant. The antibiotic efficacy and vancomycin release should be further studied using ocular in vivo models.

Matched MeSH terms: Delayed-Action Preparations/pharmacology
Probing the effects of fish oil on the delivery and inflammation-inducing potential of imiquimod

Rehman K, Aluwi MF, Rullah K, Wai LK, Mohd Amin MC, Zulfakar MH

Int J Pharm, 2015 Jul 25;490(1-2):131-41.
PMID: 26003416 DOI: 10.1016/j.ijpharm.2015.05.045

Imiquimod is a chemotherapeutic agent for many skin-associated diseases, but it has also been associated with inflammatory side effects. The aim of this study was to prevent the inflammatory effect of commercial imiquimod (Aldara(®)) by controlled release of imiquimod through a hydrogel/oleogel colloidal mixture (CA bigel) containing fish oil as an anti-inflammatory agent. Imiquimod permeability from Aldara® cream and bigel through mice skin was evaluated, and the drug content residing in the skin via the tape stripping technique was quantified. The fish oil fatty acid content in skin along with its lipophilic environment was also determined. An inflammation study was conducted using animal models, and Aldara(®) cream was found to potentially cause psoriasis-like inflammation, which could be owing to prolonged application and excessive drug permeation. Controlled release of imiquimod along with fish oil through CA bigel may have caused reduced imiquimod inflammation. NMR studies and computerized molecular modeling were also conducted to observe whether the fish oil and imiquimod formed a complex that was responsible for improving imiquimod transport and reducing its side effects. NMR spectra showed dose-dependent chemical shifts and molecular modeling revealed π-σ interaction between EPA and imiquimod, which could help reduce imiquimod inflammation.

Matched MeSH terms: Delayed-Action Preparations/pharmacology
Fulltext Antimicrobial and controlled release studies of a novel nystatin conjugated iron oxide nanocomposite

Hussein-Al-Ali SH, El Zowalaty ME, Kura AU, Geilich B, Fakurazi S, Webster TJ, et al.

Biomed Res Int, 2014;2014:651831.
PMID: 24900976 DOI: 10.1155/2014/651831

Nystatin is a tetraene diene polyene antibiotic showing a broad spectrum of antifungal activity. In the present study, we prepared a nystatin nanocomposite (Nyst-CS-MNP) by loading nystatin (Nyst) on chitosan (CS) coated magnetic nanoparticles (MNPs). The magnetic nanocomposites were characterized by X-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), thermogravimetry analysis (TGA), vibrating sample magnetometer (VSM), and scanning electron microscopy (SEM). The XRD results showed that the MNPs and nanocomposite are pure magnetite. The FTIR analysis confirmed the binding of CS on the surface of the MNPs and also the loading of Nyst in the nanocomposite. The Nyst drug loading was estimated using UV-Vis instrumentation and showing a 14.9% loading in the nanocomposite. The TEM size image of the MNPs, CS-MNP, and Nyst-CS-MNP was 13, 11, and 8 nm, respectively. The release profile of the Nyst drug from the nanocomposite followed a pseudo-second-order kinetic model. The antimicrobial activity of the as-synthesized Nyst and Nyst-CS-MNP nanocomposite was evaluated using an agar diffusion method and showed enhanced antifungal activity against Candida albicans. In this manner, this study introduces a novel nanocomposite that can decrease fungus activity on-demand for numerous medical applications.

Matched MeSH terms: Delayed-Action Preparations/pharmacology
Development of biodegradable sustained-release damnacanthal nanocapsules for potential application in in-vitro breast cancer studies

Mohd MR, Ariff TM, Mohamad N, Abdul Latif AZ, Wan Nik WMN, Mohamed A, et al.

Pak J Pharm Sci, 2019 Sep;32(5):2155-2162.
PMID: 31813882

The "noni" species of Morinda citrifolia L., is using in traditional medicine in the tropical country for over 2000 years. Noni fruit has come from the Morinda citrifolia tree which is called Rubiaceae, and it is from the coffee family. It is a perennial herb whose ripe fruit has a robust butyric acid smell and flavor. Recently scientists have proven that this fruit has antioxidant and antibiotic properties in vitro. An anthraquinone, damnacanthal, is one of the constituents of Morinda citrifolia. It has been demonstrated to have anti-cancer properties. Damnacanthal has low water solubility and low bioavailability. Formulating of damnacanthal into the biodegradable nanocapsule drug delivery system may increase its bioavailability. Various formulations of damnacanthal would be developed to enable the selection of a dosage form that could offer the provision of the anti-cancer bioactive substance with suitable sustained- or controlled release properties. The efficiency of extraction of damnacanthal will be compared using both conventional and traditional method. Both the damnacanthal and an anthraquinone active compounds extracted from noni roots, are currently being studied in the context of anti-cancer study. Soon, the medical values, bioactivities and nutritional of this fruit can be assessed, especially its anti-cancer activity, this fruit extract could play an outstanding economic role in Malaysia and other tropical countries.

Matched MeSH terms: Delayed-Action Preparations/pharmacology*
Carboxymethyl fenugreek galactomannan-g-poly(N-isopropylacrylamide-co-N,N'-methylene-bis-acrylamide)-clay based pH/temperature-responsive nanocomposites as drug-carriers

Bera H, Abbasi YF, Gajbhiye V, Liew KF, Kumar P, Tambe P, et al.

Mater Sci Eng C Mater Biol Appl, 2020 May;110:110628.
PMID: 32204068 DOI: 10.1016/j.msec.2020.110628

The current study dealt with the synthesis and characterization of carboxymethyl fenugreek galactomannang-g-poly(N-isopropylacrylamide-co-N,N'-methylene-bis-acrylamide)-bentonite [CFG-g-P(NIPA-co-MBA)-BEN] based nanocomposites (NCs) as erlotinib (ERL)-delivery devices for lung cancer cells to suppress excessive cell proliferation. The blank NCs exhibited outstanding biodegradability and pH/temperature-dependent swelling profiles, which were significantly influenced by their BEN contents (0-20%). The molar mass (M¯c) between the crosslinks of these NCs was declined with temperature. The composite architecture of these scaffolds was confirmed by XRD, FTIR, TGA, DSC and SEM analyses. The corresponding ERL-loaded matrices (F-1-F-3) portrayed outstanding drug encapsulation efficiency (DEE, 93-100%) with zeta potential between -8 and -16 mV and diameter between 615 and 1258 nm. These formulations demonstrated sustained ERL elution profiles (Q8h, 62-98%) with an initial burst release of drug. The drug dissolution pattern of the optimized matrices (F-3) obeyed first-order kinetic model and was driven by Fickian diffusion. The mucin adsorption behavior of F-3 was best fitted to Freudlich isotherms. The ERL-loaded formulation suppressed A549 cell proliferation and promoted apoptosis to a greater extent than the pristine drug, as detected by cellular uptake analysis, MTT cytotoxicity test and AO/EB staining assay.

Matched MeSH terms: Delayed-Action Preparations/pharmacology
Fulltext Sustained release of anticancer agent phytic acid from its chitosan-coated magnetic nanoparticles for drug-delivery system

Barahuie F, Dorniani D, Saifullah B, Gothai S, Hussein MZ, Pandurangan AK, et al.

Int J Nanomedicine, 2017;12:2361-2372.
PMID: 28392693 DOI: 10.2147/IJN.S126245

Chitosan (CS) iron oxide magnetic nanoparticles (MNPs) were coated with phytic acid (PTA) to form phytic acid-chitosan-iron oxide nanocomposite (PTA-CS-MNP). The obtained nanocomposite and nanocarrier were characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, vibrating sample magnetometry, transmission electron microscopy, and thermogravimetric and differential thermogravimetric analyses. Fourier transform infrared spectra and thermal analysis of MNPs and PTA-CS-MNP nanocomposite confirmed the binding of CS on the surface of MNPs and the loading of PTA in the PTA-CS-MNP nanocomposite. The coating process enhanced the thermal stability of the anticancer nanocomposite obtained. X-ray diffraction results showed that the MNPs and PTA-CS-MNP nanocomposite are pure magnetite. Drug loading was estimated using ultraviolet-visible spectroscopy and showing a 12.9% in the designed nanocomposite. Magnetization curves demonstrated that the synthesized MNPs and nanocomposite were superparamagnetic with saturation magnetizations of 53.25 emu/g and 42.15 emu/g, respectively. The release study showed that around 86% and 93% of PTA from PTA-CS-MNP nanocomposite could be released within 127 and 56 hours by a phosphate buffer solution at pH 7.4 and 4.8, respectively, in a sustained manner and governed by pseudo-second order kinetic model. The cytotoxicity of the compounds on HT-29 colon cancer cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The HT-29 cell line was more sensitive against PTA-CS-MNP nanocomposite than PTA alone. No cytotoxic effect was observed on normal cells (3T3 fibroblast cells). This result indicates that PTA-CS-MNP nanocomposite can inhibit the proliferation of colon cancer cells without causing any harm to normal cell.

Matched MeSH terms: Delayed-Action Preparations/pharmacology
Fulltext In vitro delivery and controlled release of Doxorubicin for targeting osteosarcoma bone cancer

Kamba SA, Ismail M, Hussein-Al-Ali SH, Ibrahim TA, Zakaria ZA

Molecules, 2013 Aug 30;18(9):10580-98.
PMID: 23999729 DOI: 10.3390/molecules180910580

Drug delivery systems are designed to achieve drug therapeutic index and enhance the efficacy of controlled drug release targeting with specificity and selectivity by successful delivery of therapeutic agents at the desired sites without affecting the non-diseased neighbouring cells or tissues. In this research, we developed and demonstrated a bio-based calcium carbonate nanocrystals carrier that can be loaded with anticancer drug and selectively deliver it to cancer cells with high specificity by achieving the effective osteosarcoma cancer cell death without inducing specific toxicity. The results showed pH sensitivity of the controlled release characteristics of the drug at normal physiological pH 7.4 with approximately 80% released within 1,200 min but when exposed pH 4.8 the corresponding 80% was released in 50 min. This study showed that the DOX-loaded CaCO₃ nanocrystals have promising applications in delivery of anticancer drugs.

Matched MeSH terms: Delayed-Action Preparations/pharmacology