Polysaccharide-Based Hydrogel from Seeds of Artemisia vulgaris: Extraction Optimization by Box-Behnken Design, pH-Responsiveness, and Sustained Drug Release

The current research work focuses on the extraction and optimization of the hydrogel (AVM) from the seeds of Artemisia vulgaris using Box–Behnken design-response surface methodology (BBD-RSM). The AVM was obtained through a hot water extraction process. The influence of different factors, including pH (U = 4 to 10), temperature (V = 25 to 110 °C), seed/water ratio, i.e., S/W ratio (W = 1/10 to 1/70 w/v), and seed/water contact time, i.e., S/W time (X = 1 to 12 h) on the yield of AVM was evaluated. The p-value for the analysis of variance (ANOVA) was found to be \u3c0.001, indicating that the yield of AVM mainly depended on the abovementioned factors. The highest yield of AVM, i.e., 15.86%, was found at a pH of 7.12, temperature of 80.04 °C, S/W ratio of 1/33.24 w/v, and S/W time of 8.73 h according to Design-Expert Software. The study of the pH-responsive behavior of AVM in tablet form (formulation AVT3) revealed that AVM is a pH-responsive material with significantly high swelling at pH 7.4. However, less swelling was witnessed at pH 1.2. Moreover, AVM was found to be a sustained release material for esomeprazole at pH 7.4 for 12 h. The drug release from AVT3 was according to the super case-II transport mechanism and zero-order kinetics

Design, Synthesis, Molecular Modeling, and Biological Evaluation of Novel Pyrimidine Derivatives as Potential Calcium Channel Blockers

Pyrimidines play an important role in modern medical fields. They have a wide spectrum of biological activities such as antimicrobial, anticancer, anti-allergic, anti-leishmanial, antioxidant agents and others. Moreover, in recent years, 3,4-dihydropyrimidin-2(1H)ones have attracted researchers to synthesize them via Biginelli reaction and evaluate their antihypertensive activities as bioisosters of Nifedipine, which is a famous calcium channel blocker. Our new target compounds were prepared through one-pot reaction of thiourea 1, ethyl acetoacetate 2 and/or 1H-indole-2-carbaldehyde, 2-chloroquinoline-3-carbaldehyde, 1,3-diphenyl-1H-pyrazole-4-carbaldehyde, 3a–c in acid medium (HCl) yielding pyrimidines 4a–c, which in turn were hydrolyzed to carboxylic acid derivatives 5a–c which were chlorinated by SOCl2 to give acyl chlorides 6a–c. Finally, the latter were reacted with some selected aromatic amines, namely, aniline, p-toluidine and p-nitroaniline, producing amides 7a–c, 8a–c, and 9a–c. The purity of the prepared compounds was examined via TLC monitoring, and structures were confirmed by different spectroscopic techniques such as IR, 1HNMR, 13CNMR, and mass spectroscopy. The in vivo evaluation of the antihypertensive activity revealed that compounds 4c, 7a, 7c, 8c, 9b and 9c had comparable antihypertensive properties with Nifedipine. On the other hand, the in vitro calcium channel blocking activity was evaluated by IC50 measurement and results revealed that compounds 4c, 7a, 7b, 7c, 8c, 9a, 9b, and 9c had comparable calcium channel blocking activity with the reference Nifedipine. Based on the aforementioned biological results, we selected compounds 8c and 9c to be docked onto Ryanodine and dihydropyridine receptors. Furthermore, we developed a structure–activity relationship. The designed compounds in this study show promising activity profiles in reducing blood pressure and as calcium channel blockers, and could be considered as new potential antihypertensive and/or antianginal agents

Formulation and Evaluation of Moxifloxacin Loaded Bilosomes In-Situ Gel: Optimization to Antibacterial Evaluation

In this study, moxifloxacin (MX)-loaded bilosome (BS) in situ gel was prepared to improve ocular residence time. MX-BSs were prepared using the thin-film hydration method. They were optimized using a Box–Behnken design (BBD) with bile salt (A, sodium deoxycholate), an edge activator (B, Cremophor EL), and a surfactant (C, Span 60) as process variables. Their effects were assessed based on hydrodynamic diameter (Y1), entrapment efficacy (Y2), and polydispersity index (Y3). The optimized formulation (MX-BSop) depicted a low hydrodynamic diameter (192 ± 4 nm) and high entrapment efficiency (76 ± 1%). Further, MX-BSop was successfully transformed into an in situ gel using chitosan and sodium alginate as carriers. The optimized MX-BSop in situ gel (MX-BSop-Ig4) was further evaluated for gelling capacity, clarity, pH, viscosity, in vitro release, bio-adhesiveness, ex vivo permeation, toxicity, and antimicrobial properties. MX-BSop-Ig4 exhibited an optimum viscosity of 65.4 ± 5.3 cps in sol and 287.5 ± 10.5 cps in gel states. The sustained release profile (82 ± 4% in 24 h) was achieved with a Korsmeyer–Peppas kinetic release model (R2 = 0.9466). Significant bio-adhesion (967.9 dyne/cm2) was achieved in tear film. It also exhibited 1.2-fold and 2.8-fold higher permeation than MX-Ig and a pure MX solution, respectively. It did not show any toxicity to the tested tissue, confirmed by corneal hydration (77.3%), cornea histopathology (no internal changes), and a HET-CAM test (zero score). MX-BSop-Ig4 exhibited a significantly (p < 0.05) higher antimicrobial effect than pure MX against Staphylococcus aureus and Escherichia coli. The findings suggest that bilosome in situ gel is a good alternative to increase corneal residence time, as well as to improve therapeutic activity

Anandamide Reuptake Inhibitor (VDM11) as a Possible Candidate for COVID-19 Associated Depression; a Combination of Network Pharmacology, Molecular Docking and In Vivo Experimental Analysis

Objective: Post-COVID 19 depression has gained much attention due to the increasing percentage of depressive symptoms reported by COVID-19 survivors. Among many factors postulated to be responsible for this depression, neuroinflammation gained the most attention. Therefore, in current work, we selected an anandamide reuptake inhibitor, VDM11, as a possible candidate for managing post-COVID depression. Methods: The role of VDM11 in attenuating neuroinflammation was established by using network pharmacology, molecular docking, and an in vivo LPS-induced depression model. Results: The results of network pharmacology revealed that among all the genes that can be targeted by VDM11, 47 genes were directly linked to the pathophysiology of depression. Additionally, on the basis of protein–protein interaction (PPI) analysis, the top 10 hub genes probably responsible for VDM11 antidepressant attribute were screened. These genes include MAPK3, TNF-α, IL-1β, IL-6, PPARG, MAPK1, CNR1, MTOR, NR3C1, and IGF1R. These genes were also enriched in GO and KEGG analysis. Molecular docking was carried out with top five hub genes screened by PPI network and KEGG analysis which showed that VDM11 interacts well with these targets. The antidepressant potential of VDM11 was also assessed by employing a LPS-induced depression model. Animals provided with VDM11 demonstrated increased exploration time and spontaneous alterations in elevated plus and Y maze models. Additionally, the level of astrocyte marker GFAP, microglia marker CD11b, and proinflammatory cytokines, including TNFα, IL-1β, and IL-6, in the hippocampus were significantly reduced by VDM11, further strengthening its role in neuroinflammation. Conclusion: VDM11, an anandamide reuptake inhibitor, might serve as a possible candidate for post-COVID depression, probably by modulating neuroinflammation. However, detailed pharmacological studies are required to validate these outcomes

Recent Advancement in Chitosan-Based Nanoparticles for Improved Oral Bioavailability and Bioactivity of Phytochemicals: Challenges and Perspectives

The excellent therapeutic potential of a variety of phytochemicals in different diseases has been proven by extensive studies throughout history. However, most phytochemicals are characterized by a high molecular weight, poor aqueous solubility, limited gastrointestinal permeability, extensive pre-systemic metabolism, and poor stability in the harsh gastrointestinal milieu. Therefore, loading of these phytochemicals in biodegradable and biocompatible nanoparticles (NPs) might be an effective approach to improve their bioactivity. Different nanocarrier systems have been developed in recent decades to deliver phytochemicals. Among them, NPs based on chitosan (CS) (CS-NPs), a mucoadhesive, non-toxic, and biodegradable polysaccharide, are considered the best nanoplatform for the oral delivery of phytochemicals. This review highlights the oral delivery of natural products, i.e., phytochemicals, encapsulated in NPs prepared from a natural polymer, i.e., CS, for improved bioavailability and bioactivity. The unique properties of CS for oral delivery such as its mucoadhesiveness, non-toxicity, excellent stability in the harsh environment of the GIT, good solubility in slightly acidic and alkaline conditions, and ability to enhance intestinal permeability are discussed first, and then the outcomes of various phytochemical-loaded CS-NPs after oral administration are discussed in detail. Furthermore, different challenges associated with the oral delivery of phytochemicals with CS-NPs and future directions are also discussed

Formulation and Evaluation of Topical Nano-Lipid-Based Delivery of Butenafine: In Vitro Characterization and Antifungal Activity

The present research work was designed to prepare butenafine (BN)-loaded bilosomes (BSs) by the thin-film hydration method. BN is a sparingly water-soluble drug having low permeability and bioavailability. BSs are lipid-based nanovesicles used to entrap water-insoluble drugs for enhanced permeation across the skin. BSs were prepared by the thin-film hydration method and optimized by the Box–Behnken design (BBD) using lipid (A), span 60 (B), and sodium deoxycholate (C) as independent variables. The selected formulation (BN-BSo) was converted into the gel using Carbopol 940 as a gelling agent. The prepared optimized gel (BN-BS-og) was further evaluated for the gel characterization, drug release, drug permeation, irritation, and anti-fungal study. The optimized bilosomes (BN-BSo) showed a mean vesicle size of 215 ± 6.5 nm and an entrapment efficiency of 89.2 ± 1.5%. The DSC study showed that BN was completely encapsulated in the BS lipid matrix. BN-BSog showed good viscosity, consistency, spreadability, and pH. A significantly (p < 0.05) high release (81.09 ± 4.01%) was achieved from BN-BSo compared to BN-BSog (65.85 ± 4.87%) and pure BN (17.54 ± 1.37 %). The permeation study results revealed that BN-BSo, BN-BSog, and pure BN exhibited 56.2 ± 2.7%, 39.2 ± 2.9%, and 16.6 ± 2.3%. The enhancement ratio of permeation flux was found to be 1.4-fold and 3.4-fold for the BN-BS-og and pure BN dispersion. The HET-CAM study showed that BN-BSog was found to be nonirritant as the score was found within the limit. The antifungal study revealed a significant (p < 0.05) enhanced antifungal activity against C. albicans and A. niger. The findings of the study revealed that BS is an important drug delivery system for transdermal delivery

Preparation of NLCs-Based Topical Erythromycin Gel: In Vitro Characterization and Antibacterial Assessment

In the present study, erythromycin (EM)-loaded nanostructured lipid carriers (NLCs) were prepared by the emulsification and ultra-sonication method. EM-NLCs were optimized by central composite design using the lipid (A), pluronic F127 (B) and sonication time (C) as independent variables. Their effects were evaluated on particle size (Y1) and entrapment efficiency (Y2). The optimized formulation (EM-NLCs-opt) showed a particle size of 169.6 ± 4.8 nm and entrapment efficiency of 81.7 ± 1.4%. EM-NLCs-opt further transformed into an in-situ gel system by using the carbopol 940 and chitosan blend as a gelling agent. The optimized EM-NLCs in situ gel (EM-NLCs-opt-IG4) showed quick gelation and were found to be stable for more than 24 h. EM-NLCs-opt-IG4 showed prolonged drug release compared to EM in situ gel. It also revealed significant high permeation (56.72%) and flux (1.51-fold) than EM in situ gel. The irritation and hydration study results depicted no damage to the goat cornea. HET-CAM results also confirmed its non-irritant potential (zero score). EM-NLCs-opt-IG4 was found to be isotonic and also showed significantly (p < 0.05) higher antimicrobial activity than EM in situ gel. The findings of the study concluded that NLCs laden in situ gel is an alternative delivery of erythromycin for the treatment of bacterial conjunctivitis

Development and Optimization of Hybrid Polymeric Nanoparticles of Apigenin: Physicochemical Characterization, Antioxidant Activity and Cytotoxicity Evaluation

Breast cancer is the most common cancer in females and ranked second after skin cancer. The use of natural compounds is a good alternative for the treatment of breast cancer with less toxicity than synthetic drugs. The aim of the present study is to develop and characterize hybrid Apigenin (AN) Nanoparticles (NPs) for oral delivery (AN-NPs). The hybrid AN-NPs were prepared by the self-assembly method using lecithin, chitosan and TPGS. Further, the NPs were optimized by Box-Behnken design (3-factor, 3-level). The hybrid NPs were evaluated for particle size (PS), entrapment efficiency (EE), zeta potential (ZP), and drug release. The optimized hybrid NPs (ON2), were further evaluated for solid state characterization, permeation, antioxidant, cytotoxicity and antimicrobial study. The formulation (ON2) exhibited small PS of 192.6 ± 4.2 nm, high EE 69.35 ± 1.1%, zeta potential of +36.54 mV, and sustained drug release (61.5 ± 2.5% in 24 h), as well as significantly (p 50 of pure AN was found to be significantly (p p Bacillus subtilis and Salmonella typhimurium. From these findings, it revealed that a hybrid AN polymeric nanoparticle is a good carrier for the treatment of breast cancer

Antibiotic-Loaded Psyllium Husk Hemicellulose and Gelatin-Based Polymeric Films for Wound Dressing Application

Wound infections are one of the major reasons for the delay in the healing of chronic wounds and can be overcome by developing effective wound dressings capable of absorbing exudate, providing local antibiotic release, and improving patient comfort. Arabinoxylan (AX) is a major hemicellulose present in psyllium seed husk (PSH) and exhibits promising characteristics for developing film dressings. Herein, AX-gelatin (GL) films were prepared by blending AX, gelatin (GL), glycerol, and gentamicin (antibiotic). Initially, the optimal quantities of AX, GL, and glycerol for preparing transparent, bubble-free, smooth, and foldable AX-GL films were found. Physiochemical, thermal, morphological, drug release, and antibacterial characteristics of the AX-GL films were evaluated to investigate their suitability as wound dressings. The findings suggested that the mechanical, water vapor transmission, morphological, and expansion characteristics of the optimized AX-GL films were within the required range for wound dressing. The results of Fourier-transform infrared (FTIR) analyses suggested chemical compatibility among the ingredients of the films. In in vitro drug release and antibacterial activity experiments, gentamicin (GM)-loaded AX-GL films released approximately 89% of the GM in 24 h and exhibited better antibacterial activity than standard GM solution. These results suggest that AX-GL films could serve as a promising dressing to protect against wound infections

Antibiotic-Loaded Psyllium Husk Hemicellulose and Gelatin-Based Polymeric Films for Wound Dressing Application

Wound infections are one of the major reasons for the delay in the healing of chronic wounds and can be overcome by developing effective wound dressings capable of absorbing exudate, providing local antibiotic release, and improving patient comfort. Arabinoxylan (AX) is a major hemicellulose present in psyllium seed husk (PSH) and exhibits promising characteristics for developing film dressings. Herein, AX-gelatin (GL) films were prepared by blending AX, gelatin (GL), glycerol, and gentamicin (antibiotic). Initially, the optimal quantities of AX, GL, and glycerol for preparing transparent, bubble-free, smooth, and foldable AX-GL films were found. Physiochemical, thermal, morphological, drug release, and antibacterial characteristics of the AX-GL films were evaluated to investigate their suitability as wound dressings. The findings suggested that the mechanical, water vapor transmission, morphological, and expansion characteristics of the optimized AX-GL films were within the required range for wound dressing. The results of Fourier-transform infrared (FTIR) analyses suggested chemical compatibility among the ingredients of the films. In in vitro drug release and antibacterial activity experiments, gentamicin (GM)-loaded AX-GL films released approximately 89% of the GM in 24 h and exhibited better antibacterial activity than standard GM solution. These results suggest that AX-GL films could serve as a promising dressing to protect against wound infections