Curcumin Encapsulation in Geranium Oil Microemulsion Elevates Its Antibacterial, Antioxidant, Anti-Inflammatory, and Anticancer Activities.

One of the major challenges with curcumin is its poor solubility in water, which limits its absorption and bioavailability in the body. This study aimed to develop and characterize stable microemulsions (MEs) as MEs increase the dispersibility of curcumin in water and aid its absorption in the body. Curcumin-loaded MEs were developed with the goal of enhancing topical delivery and its pharmacological activity (antioxidant, antibacterial, anticancer activity, and anti-inflammatory). The pseudoternary phase diagram was constructed to find out the desired microemulsion region. The prepared MEs (ME1-ME5) were evaluated for pH, viscosity, size of the particle, electrical conductivity, zeta potential, and ex vivo permeation of the drug. The optimized ME formulation was selected based on particle size and was further evaluated for biological activity (in vitro/vivo). In vitro cytotoxic effects of formulations were checked on the human liver cancer cell line, HEPG2 (a cell line exhibiting epithelial-like morphology that was isolated from a hepatocellular carcinoma). Geranium oil, Tween 80 (as a surfactant), and propylene glycol (as a cosurfactant) were screened out based on solubility to formulate MEs. The optimized ME formulation (ME5), with a composition of 20:50:30 (geranium oil:Tween 80:propylene glycol), exhibited pH 4.36 ± 0.057, conductivity of 40.06 ± 0.05 µS/cm, viscosity of 165 ± 0.37 mPa·s, and droplet diameter of 199.39 ± 0.017 nm. The ex vivo permeation study demonstrated a significant cumulative amount of curcumin permeated in 24 h and had a flux of 130.91 ± 0.02 µg/cm2/h. Antioxidant activity demonstrated that curcumin-loaded microemulsion (ME5) exhibited higher scavenging activity (99.27 ± 0.021%) than blank microemulsion (94.67 ± 0.001%). Optimized curcumin-loaded microemulsion (ME5) exhibited zones of inhibition of 25.18 and 28.37 mm against Escherichia coli and Staphylococcus aureus, respectively. Among the cell lines tested, a higher concentration of ME5 showed the greatest cytotoxicity with a % viability of 8.22 ± 1.09%. Evidently, it also revealed significant in vivo anti-inflammatory effects with 93.29 ± 0.030% inhibition by the carrageenan-induced paw edema model (6 h study) and 88.39 ± 0.002% inhibition by the formalin-induced paw edema model (14 day study). In conclusion, microemulsion was safe and effective for effective delivery of curcumin with the potential for antioxidant, antibacterial, cytotoxic, and in vivo anti-inflammatory activities.

Nanosizing of Lavender, Basil, and Clove Essential Oils into Microemulsions for Enhanced Antioxidant Potential and Antibacterial and Antibiofilm Activities.

Plant essential oils (EOs) possess significant bioactivities (antibacterial and antioxidant) and can be substituted for potentially harmful synthetic preservatives in the food industry. However, limited water solubility, bioavailability, volatility, and stability limit their use. Therefore, the goal of this research was nanosizing lavender essential oil (LEO), basil essential oil (BEO), and clove essential oil (CEO) in a microemulsion (ME) to improve their physicochemical attributes and bioefficacy. Tween 80 and Transcutol P were utilized for construction of pseudoternary phase diagrams. It was observed that the concentration of EOs had a great impact on the physicochemical and biological properties of MEs. A spherical droplet of MEs with a diameter of less than 20 nm with a narrower size distribution (polydispersity index (PDI) = 0.10-0.27) and a ζ potential of -0.27 to -9.03 was observed. ME formulations were also evaluated for viscosity, conductivity, and the refractive index. Moreover, the impact of delivery systems on the antibacterial property of EOs was assessed by determining the zone of inhibition and minimum inhibitory concentration against two distinct pathogen classes (S. aureus and E. coli). Crystal violet assay was used to measure the growth and development of biofilms. According to bioefficacy assays, ME demonstrated more efficient antibacterial activity against microorganisms at concentrations lower than pure EOs. CEO ME had superior activity againstS. aureus and E. coli. Similarly, dose-dependent antioxidant capacity was noted for MEs. Consequently, nanosized EO formulations with improved physicochemical properties and enhanced bioactivities can be employed in the food processing sector as a preservation agent.

Curcumin-Loaded Bioactive Polymer Composite Film of PVA/Gelatin/Tannic Acid Downregulates the Pro-inflammatory Cytokines to Expedite Healing of Full-Thickness Wounds.

Curcumin (Cur) entrapped poly(vinyl alcohol) (PVA)/gelatin composite films were prepared by cross-linking with tannic acid (TA) as bioactive dressings for rapid wound closure. Films were evaluated for mechanical strength, swelling index, water vapor transmission rate (WVTR), film solubility, and in-vitro drug release studies. SEM revealed uniform and smooth surfaces of blank (PG9) and Cur-loaded composite films (PGC4). PGC4 exhibited excellent mechanical strength (tensile strength (TS) and Young's modulus (YM) were 32.83 and 0.55 MPa, respectively), swelling ability (600-800% at pH 5.4, 7.4, and 9), WVTR (2003 ± 26), and film solubility (27.06 ± 2.0). Sustained release (81%) of the encapsulated payload was also observed for 72 h. The antioxidant activity determined by DPPH free radical scavenging showed that the PGC4 possessed strong % inhibition. The PGC4 formulation displayed higher antibacterial potential against S. aureus (14.55 mm zone of inhibition) and E. coli (13.00 mm zone of inhibition) compared to blank and positive control by the agar well diffusion method. An in-vivo wound healing study was carried out on rats using a full-thickness excisional wound model. Wounds treated with PGC4 showed very rapid healing about 93% in just 10 days post wounding as compared to 82.75% by Cur cream and 80.90% by PG9. Furthermore, histopathological studies showed ordered collagen deposition and angiogenesis along with fibroblast formation. PGC4 also exerted a strong anti-inflammatory effect by downregulating the expression of pro-inflammatory cytokines (TNF-α and IL-6 were lowered by 76% and 68% as compared to the untreated group, respectively). Therefore, Cur-loaded composite films can be an ideal delivery system for effective wound healing.

Correction to Therapeutic Potential of Standardized Extract of Melilotus indicus (L.) All. and Its Phytochemicals against Skin Cancer in Animal Model: In Vitro, In Vivo, and In Silico Studies.

[This corrects the article DOI: 10.1021/acsomega.2c03053.].

Therapeutic Potential of Standardized Extract of Melilotus indicus (L.) All. and Its Phytochemicals against Skin Cancer in Animal Model: In Vitro, In Vivo, and In Silico Studies.

Melilotus indicus (L.) All. is known to have anti-inflammatory and anticancer properties. The present study explored the in vivo skin carcinogenesis attenuating potential of ethanolic extract of M. indicus (L.) All. (Miet) in a 7,12-dimethylbenz[a]anthracene (DMBA)-induced skin cancer model. The ethanolic extract of the plant was prepared by a maceration method. HPLC analysis indicated the presence of quercetin in abundance and also various other phytoconstituents. DPPH radical scavenging assay results showed moderate antioxidant potential (IC50 = 93.55 ± 5.59 µg/mL). A topical acute skin irritation study showed the nonirritant nature of Miet. Data for the skin carcinogenic model showed marked improvement in skin architecture in Miet and its primary phytochemicals (quercetin and coumarin) treated groups. Miet 50% showed comparable effects with 5-fluorouracil. Significant (p < 0.05) anticancerous effects were seen in coumarin-quercetin combination-treated animals than in single agent (coumarin and quercetin alone)-treated animals. Chorioallantoic membrane (CAM) assay results showed the antiangiogenic potential of Miet. Treatment with Miet significantly down-regulated the serum levels of CEA (carcinoembryonic antigen) and TNF-α (Tumor necrosis factor-α). Data for the docking study indicated the binding potential of quercetin and coumarin with TNF-α, EGFR, VEGF, and BCL2 proteins. Thus, it is concluded that Miet has skin cancer attenuating potential that is proposed to be due to the synergistic actions of its bioactive molecules. Further studies to explore the effects of Miet and its bioactive molecules as an adjuvant therapy with low dose anticancer drugs are warranted, which may lead to a new area of research.

Preparation of smart PVP/HPMC based IPN hydrogel, its characterization and toxicity evaluation.

In this study, the interpenetrating polymeric network (IPN) were fabricated via free radical polymerization using polymers hydroxypropyl methylcellulose (HPMC), Polyvinylpyrrolidone (PVP) and monomer Methacrylic acid (MAA) and also investigated their influence by changing their concentrations. The developed polymeric network is crosslinked via N' N' -methylene bis-acrylamide (MBA). Different characterizations have been performed to analyze fabricated interpenetrating polymeric network structure i.e., Scanning Electron Microscopy (SEM), X-ray Powder Diffraction (XRD), Fourier-Transform Infrared Spectroscopy (FT-IR), Thermo-gravimetric Analysis (TGA) and Differential Scanning Calorimetry (DSC). Letrozole (LTZ) was loaded as a model drug in the developed system. Swelling dynamics as well as drug release behavior were thoroughly examined. FTIR studies corroborated the formation of interpenetrating polymeric network. SEM uncovered porous structure while TGA depicted enhanced thermal stability of polymeric network. PXRD depicted amorphous dispersion of LTZ. Swelling dynamics as well as LTZ release behavior from developed interpenetrating polymeric network hydrogels were dependent upon pH of the medium and concentration of pure reactants employed. Higuchi model was best fit to regression coefficient which indicated diffusion controlled mechanism of drug release. Acute oral toxicity study depicted no mortality or any signs relating to acute toxicity throughout the whole observed period. Hence, the designed interpenetrating polymeric network might turn out to be a safe and a potential carrier system for the delivery of LTZ in the treatment of breast cancer (BC).

Assessment of palmitoyl and sulphate conjugated glycol chitosan for development of polymeric micelles.

INTRODUCTION: Amphiphilic copolymers are capable of forming core shell-like structures at the critical micellar concentration (CMC); hence, they can serve as drug carriers. Thus, in the present work, polymeric micelles based on novel chitosan derivative were synthesized. METHODS: Block copolymer of palmitoyl glycol chitosan sulfate (PGCS) was prepared by grafting palmitoyl and sulfate groups serving as hydrophobic and hydrophilic fractions, respectively. Then, fourier transform infrared spectra (FTIR) and spectral changes in iodine/iodide mixture were carried out. RESULTS: FTIR studies confirmed the formation of palmitoyl glycol chitosan sulfate (PGCS) and spectral changes in iodine/iodide mixture indicated CMC which lies in the range of 0.003-0.2 mg/ml. CONCLUSION: Therefore, our study indicated that polymeric micelles based on palmitoyl glycol chitosan sulphate could be used as a prospective carrier for water insoluble drugs.

Formulation study of topically applied lotion: in vitro and in vivo evaluation.

INTRODUCTION: This article presents the development and evaluation of a new topical formulation of diclofenac diethylamine (DDA) as a locally applied analgesic lotion. METHODS: To this end, the lotion formulations were formulated with equal volume of varying concentrations (1%, 2%, 3%, 4%; v/v) of permeation enhancers, namely propylene glycol (PG) and turpentine oil (TO). These lotions were subjected to physical studies (pH, viscosity, spreadability, homogeneity, and accelerated stability), in vitro permeation, in vivo animal studies and sensatory perception testing. In vitro permeation of DDA from lotion formulations was evaluated across polydimethylsiloxane membrane and rabbit skin using Franz cells. RESULTS: It was found that PG and TO content influenced the permeation of DDA across model membranes with the lotion containing 4% v/v PG and TO content showed maximum permeation enhancement of DDA. The flux values for L4 were 1.20±0.02 µg.cm(-2).min(-1) and 0.67 ± 0.02 µg.cm(-2).min(-1) for polydimethylsiloxane and rabbit skin, respectively. Flux values were significantly different (p < 0.05) from that of the control. The flux enhancement ratio of DDA from L4 was 31.6-fold and 4.8-fold for polydimethylsiloxane and rabbit skin, respectively. In the in vivo animal testing, lotion with 4% v/v enhancer content showed maximum anti-inflammatory and analgesic effect without inducing any irritation. Sensatory perception tests involving healthy volunteers rated the formulations between 3 and 4 (values ranging between -4 to +4, indicating a range of very bad to excellent, respectively). CONCLUSION: It was concluded that the DDA lotion containing 4% v/v PG and TO exhibit the best performance overall and that this specific formulation should be the basis for further clinical investigations.