Critical Review in Designing Plant-Based Anticancer Nanoparticles against Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC), accounting for 85% of liver cancer cases, continues to be the third leading cause of cancer-related deaths worldwide. Although various forms of chemotherapy and immunotherapy have been investigated in clinics, patients continue to suffer from high toxicity and undesirable side effects. Medicinal plants contain novel critical bioactives that can target multimodal oncogenic pathways; however, their clinical translation is often challenged due to poor aqueous solubility, low cellular uptake, and poor bioavailability. Nanoparticle-based drug delivery presents great opportunities in HCC therapy by increasing selectivity and transferring sufficient doses of bioactives to tumor areas with minimal damage to adjacent healthy cells. In fact, many phytochemicals encapsulated in FDA-approved nanocarriers have demonstrated the ability to modulate the tumor microenvironment. In this review, information about the mechanisms of promising plant bioactives against HCC is discussed and compared. Their benefits and risks as future nanotherapeutics are underscored. Nanocarriers that have been employed to encapsulate both pure bioactives and crude extracts for application in various HCC models are examined and compared. Finally, the current limitations in nanocarrier design, challenges related to the HCC microenvironment, and future opportunities are also discussed for the clinical translation of plant-based nanomedicines from bench to bedside.

Newer guar gum ester/chicken feather keratin interact films for tissue engineering.

This work intends to synthesis newer guar gum indole acetate ester and design film scaffolds based on protein-polysaccharide interactions for tissue engineering applications. Guar gum indole acetate(GGIA) was synthesized for the first time from guar gum in presence of aprotic solvent activated hofmeister ions. The newer biopolymer was fully characterized in FT-IR,13C NMR, XRD and TGA analysis. High DS (Degree of Substitution, DS = 0.61) GGIA was cross-linked with hydrolyzed keratin, extracted from chicken feather wastes. Films were synthesized from different biopolymer ratios and the surface chemistry appeared interesting. Physicochemical properties for GGIA-keratin association were notable. Fully bio-based films were non-cytotoxic and exhibited excellent biocompatibility for human dermal fibroblast cell cultivations. The film scaffold showed 63% porosity and the recorded tensile strength at break was 6.4 MPa. Furthermore, the standardised film exerted superior antimicrobial activity against both the Gram-positive and Gram-negative bacteria. MICs were recorded at 130 µg/mL and 212 µg/mL for E. coli and S. aureus respectively. In summary, GGIA-keratin film scaffolds represented promising platforms for skin tissue engineering applications.

Guar gum cinnamate ouzo nanoparticles for bacterial contact killing in water environment.

Herein we report the synthesis of newer guar gum cinnamate esters (GGC) following a Hofmeister cation guided homogeneous phase reaction. High degree of substitution (DS) guar gum cinnamate was obtained using, cinnamic acid halide reactant at a 1:3 M ratio. The biopolymer was fully characterized in FT-IR,13C NMR, XRD and thermal analysis. Nanoparticles were further developed in a facile ouzo solvent diffusion technique. SEM studies confirmed quasi spherical shape of the nanoparticles (GGCN) with an average size of 200 nm. Nanoparticles GGCN, expressed antibacterial activity against water borne gram negative and gram positive bacteria. The MIC was recorded at 300 µg mL-1against Escherichia coli and 500 µg mL-1against Staphylococcus aureus. Bacterial contact killing was confirmed from the bacterial morphology studies in SEM. Thus, nanoparticles from GGC may be employed for bacterial killing and water decontamination.

Semi-interpenetrating hydrogels from carboxymethyl guar gum and gelatin for ciprofloxacin sustained release.

The present work reports the synthesis of new generation semi-interpenetrating (s-IPN) hydrogels from carboxymethyl guar gum (CMGG) and gelatin with enhanced gel properties for suitable drug delivery applications. Hydrogels are three dimensional polymer networks which respond to water and ion interactions. Irreversible s-IPN hydrogels were prepared by CMGG interactions in gelatin and characterized in FT-IR, SEM and thermal studies. CMGG was synthesized by Hofmeister ion guided homogeneous phase reactions. The swelling kinetics of the newer s-IPN hydrogels followed Schott's pseudo second order model. Furthermore, the hydrogels were hemocompatible, non-cytotoxic and appropriate for applications in physiological environment. Model drug ciprofloxacin was loaded within the hydrogels and the drug release was found to be a combination of both diffusion and hydrogel degradation. New generation s-IPN biopolymer hydrogels of carboxymethyl guar gum and gelatin holds promise for its application as sustained drug delivery device or alternatively as hydrogel sorbents for bio-toxins and molecules of biomedical importance.

Carboxymethyl guar gum synthesis in homogeneous phase and macroporous 3D scaffolds design for tissue engineering.

Guar gum (GG) is a galactomannan obtained directly from the Cyamopsis tetragonoloba seeds pericarb. The biopolymer hydrates hugely in three chain associated coil formations. Chaotropic Hofmeister ion like lithium interacts at the hydrogen bonding sites and render GG homogenization in polar solvents like dimethyl sulfoxide. This phenomenon was used for the first time for galactomannan derivatisations in homogeneous phase. Higher degree of substitution (DS) that was hereto unattainable in GG was achieved due to Hofmeister ion assisted assembly deformations. Furthermore, carboxymethyl guar gum (CMGG, DS = 1.10) blends well in poly-vinyl alcohol (PVA) at 2:1 mass ratio and enabled hydrophilic porous scaffold design for cell propagation. CMGG-PVA scaffolds porosity was 70-90% and the tensile strength was 6.32 MPa. CMGG-PVA scaffolds were useful as cell factories and in tissue engineering. New generation guar gum derivative scaffolds were non cytotoxic and permitted cell propagation in growth medium.

Andrographolide inhibits human serum albumin fibril formations through site-specific molecular interactions.

Protein misfolding and fibrillation are the fundamental traits in degenerative diseases like Alzheimer's, Parkinsonism, and diabetes mellitus. Bioactives such as flavonoids and terpenoids from plant sources are known to express protective effects against an array of diseases including diabetes, Alzheimer's and obesity. Andrographolide (AG), a labdane diterpenoid is prescribed widely in the Indian and Chinese health care systems for classical efficacy against a number of degenerative diseases. This work presents an in depth study on the effects of AG on protein fibrillating pathophysiology. Thioflavin T fluorescence spectroscopy and DLS results indicated concentration dependent inhibition of human serum albumin (HSA) fibrillation. The results were confirmed by electron microscopy studies. HSA fibril formations were markedly reduced in the presence of AG. Fluorescence studies and UV-Vis experiments confirmed further that AG molecularly interacts with HSA at site. In silico molecular docking studies revealed hydrogen bonding and hydrophobic interactions with HSA in the native state. Thus AG interacts with HSA, stabilizes the native protein structure and inhibits fibrillation. The results demonstrated that the compound possesses anti-amyloidogenic properties and can be promising against some human degenerative diseases.

Guar gum benzoate nanoparticle reinforced gelatin films for enhanced thermal insulation, mechanical and antimicrobial properties.

This work relates to guar gum benzoate self assembly nanoparticles synthesis and nano composite films development with gelatin. Guar gum benzoate was synthesized in a Hofmeister cation guided homogeneous phase reaction. Self assembly polysaccharide nanoparticles were prepared in solvent displacement technique. Electron microscopy and DLS study confirmed uniform quasi spherical nanoparticles with ζ-potential - 28.7mV. Nanocomposite films were further developed in gelatin matrix. The film capacity augmenting due to nanoparticles incorporation was noteworthy. Superior barrier properties, reinforcing and thermal insulation effects were observed in films dispersed with 20% w/w nanoparticles. Detailed FTIR studies and thermal analysis confirmed nanoparticles interactions in the film matrix. The nanocomposite film water vapour permeability was at 0.75gmm-1kPa-1h-1, thermal conductivity 0.39Wm-1K-1 and the tensile strength were recorded at 3.87MPa. The final film expressed excellent antimicrobial properties against water born gram negative and gram positive bacteria.

Candesartan cilexetil microemulsions for transdermal delivery: formulation, in-vitro skin permeation and stability assessment.

The work investigates the formulation and evaluation of microemulsions containing olive oil, Tween 80 and isopropyl alcohol for transdermal candesartan cilexetil delivery. The pseudoternary phase diagram was constructed to determine composition of microemulsions. These formulated microemulsions were evaluated for in vitro skin permeation and stability. The microemulsion containing 72 % olive oil, 8 % water, 15 % Tween 80, and 5 % isopropylalcohol showed maximum viscosity of 29.54±0.32 mPas, average small droplet size of 180.90 nm, smaller polydispersity index of 0.37, zeta potential of -12.20 and maximum candesartan cilexetil permeation flux of 0.49±0.05 µg/cm2/h through excised porcine skin. The degradation of candesartan cilexetil microemulsions after 3 months storage was found low and its shelf-life was calculated as 3.92 years at room temperature.

Ondansetron HCl Microemulsions for Transdermal Delivery: Formulation and In Vitro Skin Permeation.

Ondansetron HCl delivery through oral route suffers due to its low bioavailability due to first-pass metabolism. Therefore, the microemulsion-based transdermal delivery may be a better substitute for it. The pseudoternary phase diagrams were constructed to determine compositions of microemulsions, and ondansetron HCl microemulsions for transdermal delivery were developed using isopropyl myristate or oleic acid as the oil phase, Tween 80 as the surfactant, and isopropyl alcohol as the cosurfactant evaluated for in vitro skin permeation through excised porcine skin. The in vitro skin permeation from these formulated microemulsions was sustained over 24 hours. The microemulsion F-8 (contained 10% of isopropyl myristate as oil phase, 8% of aqueous phase, and 82% of surfactant phase containing Tween 80 and isopropyl alcohol, 3 : 1) showed the highest permeation flux of 0.284 ± 0.003 µg/cm(2)/hour. All these microemulsions followed the Korsmeyer-Peppas model (R(2) = 0.971 to 0.998) with non-Fickian, "anomalous" mechanism over a period of 24 hours.