Fabrication of cellulose nanocrystals as potential anticancer drug delivery systems for colorectal cancer treatment.

Polysaccharide nanocrystals have great potential to be used as improved drug carriers due to their low cost, high biodegradability, and biocompatibility. This study reports the synthesis of cellulose nanocrystals (CNC) loaded with 5-fluorouracil (CNC/5FU) to evaluate their anticancer activity against colorectal cancer cells. X-ray and Fourier-transform infrared spectroscopy demonstrated that acid hydrolysis successfully degraded the amorphous cellulose to liberate the crystal regions. From transmission electron microscopy, CNC/5FU appeared as rod-like nanocrystals with an average length and width of 69.53 ± 1.14 nm and 8.13 ± 0.72 nm, respectively. The anticancer drug 5FU showed improved thermal stability after being loading onto CNC. From UV-vis spectroscopy data, the drug encapsulation efficiency in CNC/5FU was estimated to be 83.50 ± 1.52%. The drug release of CNC/5FU was higher at pH 7.4 compared to those at pH 4.2 and 1.2. From the cytotoxicity assays, CNC did not affect the viability of CCD112 colon normal cells. On the other hand, CNC/5FU exhibited anticancer effects against HCT116 and HT-29 colorectal cancer cells. The anticancer actions of CNC/5FU against HCT116 cells were then confirmed using an in vitro tumor-on-chip model and clonogenic assay. Mechanistic studies demonstrated that CNC/5FU killed the cancer cells by mainly inducing cell apoptosis and mitochondrial membrane damage. Overall, this study indicated that CNC/5FU could be a potential nanoformulation for improved drug delivery and colorectal cancer treatment.

Antimicrobial Double-Layer Wound Dressing Based on Chitosan/Polyvinyl Alcohol/Copper: In vitro and in vivo Assessment.

PURPOSE: Today, the development of wounds and their side effects has become a problematic issue in medical science research. Hydrogel-based dressings are some of the best candidates for this purpose due to their ability to keep the wound bed clean, as well as provide proper moisture, tissue compatibility and an antimicrobial effect for wound healing. On the other hand, copper and its compounds have been used experimentally for many years in studies as an antimicrobial substance. Various studies have been performed determining the antimicrobial properties of this element, during which significant effects on infection have been shown. METHODS: Chitosan/polyvinyl alcohol/copper nanofibers were successfully prepared by incorporating Cu onto a polymer electrospun using an electrospinning technique. A double-layer nanofiber composed of poly(vinyl alcohol) and chitosan incorporated with Cu nanoparticles as a protective layer and a second layer composed of polyvinylpyrrolidone (PVP) nanofibers which was adjacent to the damaged cells was prepared. The prepared nanofiber was characterized by TGA, FT-IR, TEM, SEM-EDS, and X-ray powder diffraction. The antimicrobial efficiency of the nanofibers was demonstrated through biological tests on some Gram-positive and Gram-negative bacteria. Finally, the prepared hydrogel formulations were prepared to evaluate their effect on the healing process of rat open wounds. RESULTS: In this study, data from SEM, TEM, EDS, and XRD confirmed the formation of uniform fibers with nanodiameters and the presence of Cu nanoparticles onto the electrospun nanofibers. The antibacterial activity of copper was observed against all of the selected bacteria, but the Gram-positive bacteria were more sensitive compared to Gram-negative bacteria. CONCLUSION: According to the obtained results, the hydrogel wound dressing prepared in this research can be effective in caring for open wounds in the early stages of wound healing and preventing the occurrence of prolonged open wounds.

The Potential Anticancer Activity of 5-Fluorouracil Loaded in Cellulose Fibers Isolated from Rice Straw.

INTRODUCTION: Green-based materials have been increasingly studied to circumvent off-target cytotoxicity and other side-effects from conventional chemotherapy. MATERIALS AND METHODS: Here, cellulose fibers (CF) were isolated from rice straw (RS) waste by using an eco-friendly alkali treatment. The CF network served as an anticancer drug carrier for 5-fluorouracil (5-FU). The physicochemical and thermal properties of CF, pure 5-FU drug, and the 5-FU-loaded CF (CF/5-FU) samples were evaluated. The samples were assessed for in vitro cytotoxicity assays using human colorectal cancer (HCT116) and normal (CCD112) cell lines, along with human nasopharyngeal cancer (HONE-1) and normal (NP 460) cell lines after 72-hours of treatment. RESULTS: XRD and FTIR revealed the successful alkali treatment of RS to isolate CF with high purity and crystallinity. Compared to RS, the alkali-treated CF showed an almost fourfold increase in surface area and zeta potential of up to -33.61 mV. SEM images illustrated the CF network with a rod-shaped structure and comprised of ordered aggregated cellulose. TGA results proved that the thermal stability of 5-FU increased within the drug carrier. Based on UV-spectroscopy measurements for 5-FU loading into CF, drug loading encapsulation efficiency was estimated to be 83 ±0.8%. The release media at pH 7.4 and pH 1.2 showed a maximum drug release of 79% and 46%, respectively, over 24 hours. In cytotoxicity assays, CF showed almost no damage, while pure 5-FU killed most of the both normal and cancer cells. Impressively, the drug-loaded sample of CF/5-FU at a 250 µg/mL concentration demonstrated a 58% inhibition against colorectal cancer cells, but only a 23% inhibition against normal colorectal cells. Further, a 62.50 µg/mL concentration of CF/5FU eliminated 71% and 39% of nasopharyngeal carcinoma and normal nasopharyngeal cells, respectively. DISCUSSION: This study, therefore, showed the strong potential anticancer activity of the novel CF/5-FU formulations, warranting their further investigation.

Enzymatic Synthesis of Ricinoleyl Hydroxamic Acid Based on Commercial Castor Oil, Cytotoxicity Properties and Application as a New Anticancer Agent.

BACKGROUND: New anticancer agents that rely on natural/healthy, not synthetic/toxic, components are very much needed. METHODS: Ricinoleyl hydroxamic acid (RHA) was synthesized from castor oil and hydroxylamine using Lipozyme TL IM as a catalyst. To optimize the conversion, the effects of the following parameters were investigated: type of organic solvent, period of reaction, amount of enzyme, the molar ratio of reactants and temperature. The highest conversion was obtained when the reaction was carried out under the following conditions: hexane as a solvent; reaction period of 48 hours; 120 mg of Lipozyme TL IM/3 mmol oil; HA-oil ratio of 19 mmol HA/3 mmol oil; and temperature of 40°C. The cytotoxicity of the synthesized RHA was assessed using human dermal fibroblasts (HDF), and its application towards fighting cancer was assessed using melanoma and glioblastoma cancer cells over a duration of 24 and 48 hours. RESULTS: RHA was successfully synthesized  and it demonstrated strong anticancer activity against glioblastoma and melanoma cells at as low as a 1 µg/mL concentration while it did not demonstrate any toxicity against HDF cells. CONCLUSION: This is the first report on the synthesis of RHA with great potential to be used as a new anticancer agent.

Green Synthesis of Zeolite/Fe2O3 Nanocomposites: Toxicity & Cell Proliferation Assays and Application as a Smart Iron Nanofertilizer.

PURPOSE: The aim of this study was to prepare zeolite/iron (III) oxide nanocomposites (zeolite/Fe2O3-NCs) as a smart fertilizer to improve crop yield and soil productivity. METHODS: Zeolite/Fe2O3-NCs were successfully produced by loading of Fe2O3-NPs onto the zeolite surface using a quick green precipitation method. The production of zeolite/Fe2O3 nanocomposites was performed under a mild condition using environmentally friendly raw materials as a new green chemistry method. The product was characterized using several techniques such as near and far Fourier-transform infrared spectroscopy (FT-IR), powder X-ray diffraction (PXRD), energy-dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). RESULTS: The results confirmed the formation of Fe2O3-NPs with mean particle sizes of 1.45, 2.19, and 2.20 nm on the surface of the zeolite per amount of 4, 7 and 12 wt% Fe2O3-NPs, respectively. Such results indicated that the size of the Fe2O3-NPs did not significantly change when Fe amounts increased from 7 to 12 wt% for the zeolite/Fe2O3-NCs. In terms of medical applications, in vitro cell studies demonstrated that zeolites and zeolite/Fe2O3-NCs were generally non-toxic to human fibroblast cells and significantly pernicious to human malignant melanoma cells. From MTS cytotoxicity assays, the concentration of Fe2O3 within the zeolite/Fe2O3-NCs that was effective at inhibiting the growth of malignant melanoma cells by 50% (the IC50 value) was ~14.9 wt%. The three types of nanocomposites were further tested as an iron smart nanofertilizer for the slow-release of iron ions. CONCLUSION: Advantages of this project include the production of non-toxic nanocomposites as a smart fertilizer to develop crops while the reaction involves the use of commercial and natural materials as low-cost raw materials with low energy usage due to a mild reaction condition, as well as the use of an environmentally friendly solvent (water) with no toxic residues.

Recent Developments in the Facile Bio-Synthesis of Gold Nanoparticles (AuNPs) and Their Biomedical Applications.

Gold nanoparticles (AuNPs) are extensively studied nanoparticles (NPs) and are known to have profound applications in medicine. There are various methods to synthesize AuNPs which are generally categorized into two main types: chemical and physical synthesis. Continuous efforts have been devoted to search for other more environmental-friendly and economical large-scale methods, such as environmentally friendly biological methods known as green synthesis. Green synthesis is especially important to minimize the harmful chemical and toxic by-products during the conventional synthesis of AuNPs. Green materials such as plants, fungi, microorganisms, enzymes and biopolymers are currently used to synthesize various NPs. Biosynthesized AuNPs are generally safer for use in biomedical applications since they come from natural materials themselves. Multiple surface functionalities of AuNPs allow them to be more robust and flexible when combined with different biological assemblies or modifications for enhanced applications. This review focuses on recent developments of green synthesized AuNPs and discusses their numerous biomedical applications. Sources of green materials with successful examples and other key parameters that determine the functionalities of AuNPs are also discussed in this review.

Wound dressings functionalized with silver nanoparticles: promises and pitfalls.

Infections are the main reason why most people die from burns and diabetic wounds. The clinical challenge for treating wound infections through traditional antibiotics has been growing steadily and has now reached a critical status requiring a paradigm shift for improved chronic wound care. The US Centers for Disease Control have predicted more deaths from antimicrobial-resistant bacteria than from all types of cancers combined by 2050. Thus, the development of new wound dressing materials that do not rely on antibiotics is of paramount importance. Currently, incorporating nanoparticles into scaffolds represents a new concept of 'nanoparticle dressing' which has gained considerable attention for wound healing. Silver nanoparticles (Ag-NPs) have been categorized as metal-based nanoparticles and are intriguing materials for wound healing because of their excellent antimicrobial properties. Ag-NPs embedded in wound dressing polymers promote wound healing and control microorganism growth. However, there have been several recent disadvantages of using Ag-NPs to fight infections, such as bacterial resistance. This review highlights the therapeutic approaches of using wound dressings functionalized with Ag-NPs and their potential role in revolutionizing wound healing. Moreover, the physiology of the skin and wounds is discussed to place the use of Ag-NPs in wound care into perspective.

Status of Plant Protein-Based Green Scaffolds for Regenerative Medicine Applications.

In recent decades, regenerative medicine has merited substantial attention from scientific and research communities. One of the essential requirements for this new strategy in medicine is the production of biocompatible and biodegradable scaffolds with desirable geometric structures and mechanical properties. Despite such promise, it appears that regenerative medicine is the last field to embrace green, or environmentally-friendly, processes, as many traditional tissue engineering materials employ toxic solvents and polymers that are clearly not environmentally friendly. Scaffolds fabricated from plant proteins (for example, zein, soy protein, and wheat gluten), possess proper mechanical properties, remarkable biocompatibility and aqueous stability which make them appropriate green biomaterials for regenerative medicine applications. The use of plant-derived proteins in regenerative medicine has been especially inspired by green medicine, which is the use of environmentally friendly materials in medicine. In the current review paper, the literature is reviewed and summarized for the applicability of plant proteins as biopolymer materials for several green regenerative medicine and tissue engineering applications.

A review of small molecules and drug delivery applications using gold and iron nanoparticles.

Conventional cancer treatment techniques show several limitations including low or no specificity and consequently a low efficacy in discriminating between cancer cells and healthy cells. Recent nanotechnology developments have introduced smart and novel therapeutic nanomaterials that take advantage of various targeting approaches. The use of nanotechnology in medicine and, more specifically, drug delivery is set to spread even more rapidly than it has over the past two decades. Currently, many nanoparticles (NPs) are under investigation for drug delivery including those for cancer therapy. Targeted nanomaterials bind selectively to cancer cells and greatly affect them with only a minor effect on healthy cells. Gold nanoparticles (Au-NPs), specifically, have been identified as significant candidates for new cancer therapeutic modalities because of their biocompatibility, easy functionalization and fabrication, optical tunable characteristics, and chemophysical stability. In the last decade, there has been significant research on Au-NPs and their biomedical applications. Functionalized Au-NPs represent highly attractive and promising candidates for drug delivery, owing to their unique dimensions, tunable surface functionalities, and controllable drug release. Further, iron oxide NPs due to their "superparamagnetic" properties have been studied and have demonstrated successful employment in numerous applications. In targeted drug delivery systems, drug-loaded iron oxide NPs can accumulate at the tumor site with the aid of an external magnetic field. This can lead to incremental effectiveness in drug release to the tumor site and vanquish cancer cells without harming healthy cells. In order for the application of iron oxide NPs in the human body to be realized, they should be biodegradable and biocompatible to minimize toxicity. This review illustrates recent advances in the field drug and small molecule delivery such as fluorouracil, folic acid, doxorubicin, paclitaxel, and daunorubicin, specifically when using gold and iron oxide NPs as carriers of anticancer therapeutic agents.

A review of using green chemistry methods for biomaterials in tissue engineering.

Although environmentally safe, or green, technologies have revolutionized other fields (such as consumables, automobiles, etc.), its use in biomaterials is still at its infancy. However, in the few cases in which safe manufacturing technology and materials have been implemented to prevent postpollution and reduce the consumption of synthesized scaffold (such as bone, cartilage, blood cell, nerve, skin, and muscle) has had a significant impact on different applications of tissue engineering. In the present research, we report the use of biological materials as templates for preparing different kinds of tissues and the application of safe green methods in tissue engineering technology. These include green methods for bone and tissue engineering-based biomaterials, which have received the greatest amount of citations in recent years. Thoughts on what is needed for this field to grow are also critically included. In this paper, the impending applications of safe, ecofriendly materials and green methods in tissue engineering have been detailed.

A review of drug delivery systems based on nanotechnology and green chemistry: green nanomedicine.

This review discusses the impact of green and environmentally safe chemistry on the field of nanotechnology-driven drug delivery in a new field termed "green nanomedicine". Studies have shown that among many examples of green nanotechnology-driven drug delivery systems, those receiving the greatest amount of attention include nanometal particles, polymers, and biological materials. Furthermore, green nanodrug delivery systems based on environmentally safe chemical reactions or using natural biomaterials (such as plant extracts and microorganisms) are now producing innovative materials revolutionizing the field. In this review, the use of green chemistry design, synthesis, and application principles and eco-friendly synthesis techniques with low side effects are discussed. The review ends with a description of key future efforts that must ensue for this field to continue to grow.

Benzyl and methyl fatty hydroxamic acids based on palm kernel oil as chelating agent for liquid-liquid iron(III) extraction.

Liquid-liquid iron(III) extraction was investigated using benzyl fatty hydroxamic acids (BFHAs) and methyl fatty hydroxamic acids (MFHAs) as chelating agents through the formation of iron(III) methyl fatty hydroxamate (Fe-MFHs) or iron(III) benzyl fatty hydroxamate (Fe-BFHs) in the organic phase. The results obtained under optimized conditions, showed that the chelating agents in hexane extract iron(III) at pH 1.9 were realized effectively with a high percentage of extraction (97.2% and 98.1% for MFHAs and BFHAs, respectively). The presence of a large amount of Mg(II), Ni(II), Al(III), Mn(II) and Co(II) ions did affect the iron(III) extraction. Finally stripping studies for recovering iron(III) from organic phase (Fe-MFHs or Fe-BFHs dissolved in hexane) were carried out at various concentrations of HCl, HNO(3) and H(2)SO(4). The results showed that the desired acid for recovery of iron(III) was 5 M HCl and quantitative recovery of iron(III) was achieved from Fe(III)-MFHs and Fe(III)-BFHs solutions in hexane containing 5 mg/L of Fe(III).

Enzymatic synthesis of fatty hydroxamic acid derivatives based on palm kernel oil.

Fatty hydroxamic acid derivatives were synthesized using Lipozyme TL IM catalyst at biphasic medium as the palm kernel oil was dissolved in hexane and hydroxylamine derivatives were dissolved in water: (1) N-methyl fatty hydroxamic acids (MFHAs); (2) N-isopropyl fatty hydroxamic acids (IPFHAs) and (3) N-benzyl fatty hydroxamic acids (BFHAs) were synthesized by reaction of palm kernel oil and N-methyl hydroxylamine (N-MHA), N-isopropyl hydroxylamine (N-IPHA) and N-benzyl hydroxylamine (N-BHA), respectively. Finally, after separation the products were characterized by color testing, elemental analysis, FT-IR and 1H-NMR spectroscopy. For achieving the highest conversion percentage of product the optimum molar ratio of reactants was obtained by changing the ratio of reactants while other reaction parameters were kept constant. For synthesis of MFHAs the optimum mol ratio of N-MHA/palm kernel oil = 6/1 and the highest conversion was 77.8%, for synthesis of IPFHAs the optimum mol ratio of N-IPHA/palm kernel oil = 7/1 and the highest conversion was 65.4% and for synthesis of BFHAs the optimum mol ratio of N-BHA/palm kernel oil = 7/1 and the highest conversion was 61.7%.