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

Jahangirian H, Azizi S, Rafiee-Moghaddam R, Baratvand B, Webster TJ

Biomolecules, 2019 10 17;9(10).
PMID: 31627453 DOI: 10.3390/biom9100619

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

Jahangirian H, Haron MJ, Yusof NA, Silong S, Kassim A, Rafiee-Moghaddam R, et al.

Molecules, 2011 Aug 05;16(8):6634-44.
PMID: 25134767 DOI: 10.3390/molecules16086634

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

Jahangirian H, Lemraski EG, Webster TJ, Rafiee-Moghaddam R, Abdollahi Y

Int J Nanomedicine, 2017;12:2957-2978.
PMID: 28442906 DOI: 10.2147/IJN.S127683

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

Jahangirian H, Kalantari K, Izadiyan Z, Rafiee-Moghaddam R, Shameli K, Webster TJ

Int J Nanomedicine, 2019;14:1633-1657.
PMID: 30880970 DOI: 10.2147/IJN.S184723

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.
Wound dressings functionalized with silver nanoparticles: promises and pitfalls

Kalantari K, Mostafavi E, Afifi AM, Izadiyan Z, Jahangirian H, Rafiee-Moghaddam R, et al.

Nanoscale, 2020 Jan 28;12(4):2268-2291.
PMID: 31942896 DOI: 10.1039/c9nr08234d

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

Lee KX, Shameli K, Yew YP, Teow SY, Jahangirian H, Rafiee-Moghaddam R, et al.

Int J Nanomedicine, 2020;15:275-300.
PMID: 32021180 DOI: 10.2147/IJN.S233789

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

Yusefi M, Shameli K, Jahangirian H, Teow SY, Umakoshi H, Saleh B, et al.

Int J Nanomedicine, 2020;15:5417-5432.
PMID: 32801697 DOI: 10.2147/IJN.S250047

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

Haron MJ, Jahangirian H, Silong S, Yusof NA, Kassim A, Rafiee-Moghaddam R, et al.

Int J Mol Sci, 2012;13(2):2148-59.
PMID: 22408444 DOI: 10.3390/ijms13022148

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

Yusefi M, Soon ML, Teow SY, Monchouguy EI, Neerooa BNHM, Izadiyan Z, et al.

Int J Biol Macromol, 2022 Feb 28;199:372-385.
PMID: 34998882 DOI: 10.1016/j.ijbiomac.2021.12.189

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.