Application of hyaluronic acid in tissue engineering, regenerative medicine, and nanomedicine: A review.

Hyaluronic acid (HA) plays a vital role in cellular processes and its contribution to physical and immunological barriers is considered to be an important property for the formulation of modern therapeutics. With the increasing demand for non-toxic and targeted therapy, HA-based materials could be utilized for biomedical applications due to their tendency to bio-mimic the hosts. Moreover, HA is a versatile compound in the fabrication of HA-based products such as hydrogels, nanofibers, and 3D materials. These have been implemented in various medical fields, such as bone and tissue regeneration, topical gels for wound healing, and cancer treatment via HA-loaded drug delivery approaches. Herein, we have discussed the characteristics of HA and its significance in drug delivery in addition to synergistic effects with other therapeutic compounds in the fields of nanomedicine, tissue engineering, and regenerative medicine.

Characterizations of Alpha-Cellulose and Microcrystalline Cellulose Isolated from Cocoa Pod Husk as a Potential Pharmaceutical Excipient.

Cellulose is a non-toxic, bio-degradable, and renewable biopolymer which is abundantly available in nature. The most common source of commercial microcrystalline cellulose is fibrous wood pulp. Cellulose and its derivatives have found wide commercial applications in the pharmaceutical, cosmetic, food, paper, textile, and engineering industries. This study aims to isolate and characterize cellulose forms from cocoa pod husk (CPH) and to assess its mechanical and disintegration properties as a direct compression excipient in metronidazole tablets. Two isolated cellulose types (i.e., cocoa alpha-cellulose (CAC) and cocoa microcrystalline cellulose (C-MCC)) were compared with avicel (AV). CAC and C-MCC were characterized for their physicochemical properties using Scanning Electron Microscopy (SEM), FTIR spectroscopy, Differential Scanning Calorimetry (DSC), and X-Ray Powder Diffraction (XRD). Metronidazole tablets were produced by direct compression with cellulose. The mechanical and disintegration properties of the tablets were evaluated. CAC and C-MCC yield was 42.3% w/w and 38.25% w/w, respectively. Particle diameters were significantly different with CAC (282.22 µm) > C-MCC (161.32 µm) > AV (72.51 µm). CAC and C-MCC had a better flow than AV. SEM revealed the fibrous nature of the cellulose. FTIR and XRD analysis confirmed the presence of cellulose with crystallinity index of 69.26%, 43.83%, and 26.32% for AV, C-MCC, and CAC, respectively. C-MCC and AV are more crystalline and thermally stable at high temperatures compared to CAC. The mechanical and disintegration properties of C-MCC and AV tablets complied with pharmacopeia specifications. Taken together, C-MCC isolated from CPH displayed some fundamental characteristics suitable for use as a pharmaceutical excipient and displayed better properties compared to that of AV.

Impact of industrial effluents on the environment and human health and their remediation using MOFs-based hybrid membrane filtration techniques.

The hazardous risk posed by industrial effluent discharge into the ecosystem has raised a plethora of environmental issues, public health, and safety concerns. The effluents from industries such as tanning, leather, petrochemicals, pharmaceuticals, and textiles are create significant stress on the aquatic ecosystem, which induces significant toxicity, involved in endocrine disruptions, and inhibits reproductive functions. Therefore, this review presented an overall abridgment of the effects of these effluents and their ability to synergize with modern pollutants such as pharmaceuticals, cosmetic chemicals, nanoparticles, and heavy metals. We further emphasize the metal organic framework (MOF) based membrane filtration approach for remediation of industrial effluents in comparison to the traditional remediation process. The MOF based-hybrid membrane filters provide higher reusability, better adsorption, and superior removal rates through the implication of nanotechnology, while the traditional remediation process offers poorer filtration rates and stability.

Two Promising Anti-Cancer Compounds, 2-Hydroxycinnaldehyde and 2- Benzoyloxycinnamaldehyde: Where do we stand?

Natural bioactive compounds with anti-carcinogenic activity are gaining tremendous interest in the field of oncology. Cinnamon, an aromatic condiment commonly used in tropical regions, appeared incredibly promising as an adjuvant for cancer therapy. Indeed, its whole or active parts (e.g., bark, leaf) exhibited significant anti-carcinogenic activity, which is mainly due to two cinnamaldehyde derivatives, namely 2-hydroxycinnaldehyde (HCA) and 2- benzoyloxycinnamaldehyde (BCA). In addition to their anti-cancer activity, HCA and BCA exert immunomodulatory, anti-platelets, and anti-inflammatory activities. The highly reactive α,ßunsaturated carbonyl pharmacophore, called Michael acceptor, contributes to their therapeutic effects. The molecular mechanisms underlying their anti-tumoral and anti-metastatic effects are miscellaneous, strongly suggesting that these compounds are multi-targeting compounds. Nevertheless, unravelling the exact molecular mechanisms of HCA and BCA remains a challenging matter which is necessary for optimal controlled-drug targeting delivery, safety, and efficiency. Eventually, their poor pharmacological properties (e.g., systemic bioavailability and solubility) represent a limitation and depend both on their administration route (e.g., per os, intravenously) and the nature of the formulation (e.g., free, smart nano-). This concise review focused on the potential of HCA and BCA as adjuvants in cancer. We describe their medicinal effects as well as provide an update about their molecular mechanisms reported either in-vitro, ex-vivo, or in animal models.

A comprehensive review on immuno-nanomedicine for breast cancer therapy: Technical challenges and troubleshooting measures.

Nanosized drug carriers have received a major attention in cancer therapeutics and theranostics. The immuno-nanomedicine is a combination of monoclonal antibody (mAb)/mAb-drug-nanoparticles. The immuno-nanomedicine offers a promising strategy to target cancer cells. However, the understating of nanotechnology, cancer biology, immunomedicine, and nanoparticle surface chemistry has provided a better clue to prepare the effective immuno-nanomedicine for cancer therapy. Moreover, the selection of nanoparticles type and its composition is essential for development of efficient drug delivery system (DDS) to target the cancer cell site. Immuno-nanomedicine works in the ligand-receptor binding mechanism through the interaction of mAb conjugated nanoparticles and specific antigen over expressed on target cancer cells. Therefore, the selection of specific receptors in the cancer cell and their ligand is important to prepare the active immuno-nanomedicines. Moreover, the factors such as drug loading, entrapment efficiency, size, shape, and ligand conjugation of a nanocarrier are considered as major factors for a better cancer cell, internalization, drug release, and cancer cell ablation. The target-based over-expression of antigen, mAb is engineered and conjugated with nanoparticles for successful targeting of the cancer cells without causing adverse effects to normal cells. Therefore, this review analyzed the fundamental factors in the immuno-nanomedicine for breast cancer and its technical challenges in the fabrication of the antibody alone/and drug conjugated nanoparticles.

Marine Algae-Derived Bioactive Compounds: A New Wave of Nanodrugs?

Marine algae are rich in bioactive nutraceuticals (e.g., carbohydrates, proteins, minerals, fatty acids, antioxidants, and pigments). Biotic (e.g., plants, microorganisms) and abiotic factors (e.g., temperature, pH, salinity, light intensity) contribute to the production of primary and secondary metabolites by algae. Easy, profitable, and sustainable recovery methods include novel solid-liquid and liquid-liquid extraction techniques (e.g., supercritical, high pressure, microwave, ultrasound, enzymatic). The spectacular findings of algal-mediated synthesis of nanotheranostics has attracted further interest because of the availability of microalgae-based natural bioactive therapeutic compounds and the cost-effective commercialization of stable microalgal drugs. Algal extracts can serve as stabilizing/capping and reducing agents for the synthesis of thermodynamically stable nanoparticles (NPs). Different types of nanotherapeutics have been synthesized using physical, chemical, and biological methods. Marine algae are a fascinating source of lead theranostics compounds, and the development of nanotheranostics has been linked to enhanced drug efficacy and safety. Indeed, algae are remarkable nanobiofactories, and their pragmatic properties reside in their (i) ease of handling; (ii) capacity to absorb/accumulate inorganic metallic ions; (iii) cost-effectiveness; and (iv) capacity of eco-friendly, rapid, and healthier synthesis of NPs. Preclinical and clinical trials shall enable to really define effective algal-based nanotherapies. This review aims to provide an overview of the main algal compounds that are nutraceuticals and that can be extracted and purified for nanotheranostic purposes.

Ecological and Industrial Implications of Dynamic Seaweed-Associated Microbiota Interactions.

Seaweeds are broadly distributed and represent an important source of secondary metabolites (e.g., halogenated compounds, polyphenols) eliciting various pharmacological activities and playing a relevant ecological role in the anti-epibiosis. Importantly, host (as known as basibiont such as algae)-microbe (as known as epibiont such as bacteria) interaction (as known as halobiont) is a driving force for coevolution in the marine environment. Nevertheless, halobionts may be fundamental (harmless) or detrimental (harmful) to the functioning of the host. In addition to biotic factors, abiotic factors (e.g., pH, salinity, temperature, nutrients) regulate halobionts. Spatiotemporal and functional exploration of such dynamic interactions appear crucial. Indeed, environmental stress in a constantly changing ocean may disturb complex mutualistic relations, through mechanisms involving host chemical defense strategies (e.g., secretion of secondary metabolites and antifouling chemicals by quorum sensing). It is worth mentioning that many of bioactive compounds, such as terpenoids, previously attributed to macroalgae are in fact produced or metabolized by their associated microorganisms (e.g., bacteria, fungi, viruses, parasites). Eventually, recent metagenomics analyses suggest that microbes may have acquired seaweed associated genes because of increased seaweed in diets. This article retrospectively reviews pertinent studies on the spatiotemporal and functional seaweed-associated microbiota interactions which can lead to the production of bioactive compounds with high antifouling, theranostic, and biotechnological potential.

Green and Cost-Effective Synthesis of Metallic Nanoparticles by Algae: Safe Methods for Translational Medicine.

Metal nanoparticles (NPs) have received much attention for potential applications in medicine (mainly in oncology, radiology and infectiology), due to their intriguing chemical, electronical, catalytical, and optical properties such as surface plasmon resonance (SPR) effect. They also offer ease in controlled synthesis and surface modification (e.g., tailored properties conferred by capping/protecting agents including N-, P-, COOH-, SH-containing molecules and polymers such as thiol, disulfide, ammonium, amine, and multidentate carboxylate), which allows (i) tuning their size and shape (e.g., star-shaped and/or branched) (ii) improving their stability, monodispersity, chemical miscibility, and activity, (iii) avoiding their aggregation and oxidation over time, (iv) increasing their yield and purity. The bottom-up approach, where the metal ions are reduced in the NPs grown in the presence of capping ligands, has been widely used compared to the top-down approach. Besides the physical and chemical synthesis methods, the biological method is gaining much consideration. Indeed, several drawbacks have been reported for the synthesis of NPs via physical (e.g., irradiation, ultrasonication) and chemical (e.g., electrochemisty, reduction by chemicals such as trisodium citrate or ascorbic acid) methods (e.g., cost, and/ortoxicity due to use of hazardous solvents, low production rate, use of huge amount of energy). However, (organic or inorganic) eco-friendly NPs synthesis exhibits a sustainable, safe, and economical solution. Thereby, a relatively new trend for fast and valuable NPs synthesis from (live or dead) algae (i.e., microalgae, macroalgae and cyanobacteria) has been observed, especially because of its massive presence on the Earth's crust and their unique properties (e.g., capacity to accumulate and reduce metallic ions, fast propagation). This article discusses the algal-mediated synthesis methods (either intracellularly or extracellularly) of inorganic NPs with special emphasis on the noblest metals, i.e., silver (Ag)- and gold (Au)-derived NPs. The key factors (e.g., pH, temperature, reaction time) that affect their biosynthesis process, stability, size, and shape are highlighted. Eventually, underlying molecular mechanisms, nanotoxicity and examples of major biomedical applications of these algal-derived NPs are presented.

Double deboronation and homometalation of 1,1'-bis(ortho-carborane).

Double deboronation of 1,1'-bis(ortho-carborane) results in a mixture of racemic and meso diastereoisomers which are sources of the [7-(7'-7',8'-nido-C2B9H10)-7,8-nido-C2B9H10]4- tetraanion. Consistent with this, metalation of the mixture with {Ru(p-cymene)} affords the diastereoisomers α-[1-(8'-2'-(p-cymene)-2',1',8'-closo-RuC2B9H10)-3-(p-cymene)-3,1,2-closo-RuC2B9H10] (3α) and ß-[1-(8'-2'-(p-cymene)-2',1',8'-closo-RuC2B9H10)-3-(p-cymene)-3,1,2-closo-RuC2B9H10] (3ß) in which the primed cage has undergone a spontaneous 3',1',2' to 2',1',8'-RuC2B9 isomerisation. Analogous cobaltacarboranes α-[1-(8'-2'-Cp-2',1',8'-closo-CoC2B9H10)-3-Cp-3,1,2-closo-CoC2B9H10] (4α) and ß-[1-(8'-2'-Cp-2',1',8'-closo-CoC2B9H10)-3-Cp-3,1,2-closo-CoC2B9H10] (4ß) are formed by metalation with CoCl2/NaCp followed by oxidation, along with a small amount of the unique species [8-(8'-2'-Cp-2',1',8'-closo-CoC2B9H10)-2-Cp-2,1,8-closo-CoC2B9H10] (5) if the source of the tetraanion is [HNMe3]2[7-(7'-7',8'-nido-C2B9H11)-7,8-nido-C2B9H11]. Two-electron reduction and subsequent reoxidation of 4α and 4ß afford species indistinguishable from 5. The reaction between [Tl]2[1-(1'-3',1',2'-closo-TlC2B9H10)-3,1,2-closo-TlC2B9H10] and [CoCpI2(CO)] leads to the isolation of a further isomer of (CpCoC2B9H11)2, rac-[1-(1'-3'-Cp-3',1',2'-closo-CoC2B9H10)-3-Cp-3,1,2-closo-CoC2B9H10] (6), which displays intramolecular dihydrogen bonding. Thermolysis of 6 yields 4α, allowing a link to be established between the α and ß forms of 3 and 4 and racemic and meso forms of the [7-(7'-7',8'-nido-C2B9H10)-7,8-nido-C2B9H10]4- tetraanion, whilst reduction-oxidation of 6 again results in a product indistinguishable from 5.

Icosahedral metallacarborane/carborane species derived from 1,1'-bis(o-carborane).

Examples of singly-metallated derivatives of 1,1'-bis(o-carborane) have been prepared and spectroscopically and structurally characterised. Metallation of [7-(1'-1',2'-closo-C2B10H11)-7,8-nido-C2B9H10](2-) with a {Ru(p-cymene)}(2+) fragment affords both the unisomerised species [1-(1'-1',2'-closo-C2B10H11)-3-(p-cymene)-3,1,2-closo-RuC2B9H10] (2) and the isomerised [8-(1'-1',2'-closo-C2B10H11)-2-(p-cymene)-2,1,8-closo-RuC2B9H10] (3), and 2 is easily transformed into 3 with mild heating. Metallation with a preformed {CoCp}(2+) fragment also affords a 3,1,2-MC2B9-1',2'-C2B10 product [1-(1'-1',2'-closo-C2B10H11)-3-Cp-3,1,2-closo-CoC2B9H10] (4), but if CoCl2/NaCp is used followed by oxidation the result is the 2,1,8-CoC2B9-1',2'-C2B10 species [8-(1'-1',2'-closo-C2B10H11)-2-Cp-2,1,8-closo-CoC2B9H10] (5). Compound 4 does not convert into 5 in refluxing toluene, but does do so if it is reduced and then reoxidised, perhaps highlighting the importance of the basicity of the metal fragment in the isomerisation of metallacarboranes. A computational study of 1,1'-bis(o-carborane) is in excellent agreement with a recently-determined precise crystallographic study and establishes that the {1',2'-closo-C2B10H11} fragment is electron-withdrawing compared to H.