Investigating the in-vitro bioactivity, biodegradability and drug release behavior of the newly developed PES/HA/WS biocompatible nanocomposites as bone graft substitute.

The nucleation of carbonate-containing apatite on the biomaterials surface is regarded as a significant stage in bone healing process. In this regard, composites contained hydroxyapatite (Ca10(PO4)6(OH)2, HA), wollastonite (CaSiO3, WS) and polyethersulfone (PES) were synthesized via a simple solvent casting technique. The in-vitro bioactivity of the prepared composite films with different weight ratios of HA and WS was studied by placing the samples in the simulated body fluid (SBF) for 21 days. The results indicated that the the surface of composites containing 2 wt% HA and 4 wt% WS was completely covered by a thick bone-like apatite layer, which was characterized by Grazing incidence X-ray diffraction, attenuated total reflectance-Fourier transform infrared spectrometer, field emission electron microscopy and energy dispersive X-ray analyzer (EDX). The degradation study of the samples showed that the concentration of inorganic particles could not influence the degradability of the polymeric matrix, where all samples expressed similar dexamethasone (DEX) release behavior. Moreover, the in-vitro cytotoxicity results indicated the significant cyto-compatibility of all specimens. Therefore, these findings revealed that the prepared composite films composed of PES, HA, WS and DEX could be regarded as promising bioactive candidates with low degradation rate for bone tissue engineering applications.

Development and Characterization of Thiolated Cyclodextrin-Based Nanoparticles for Topical Delivery of Minoxidil.

PURPOSE: The aim of this research was to prepare adhesive nanoparticles for the topical application of Minoxidil (MXD). METHODS: Thiolated ß-CDs were prepared via conjugation of cysteamine with oxidized CDs. MXD was encapsulated within thiolated and unmodified ß-CDs. Ionic gelation method was used to prepare nanoparticles (Thio-NP and blank NP) of CDs with chitosan. Nanoparticles were analyzed for size and zetapotential. Inclusion complexes were characterized via FTIR. Drug dissolution studies were carried out. An in vitro adhesion study over human hair was performed. An in vivo skin irritation study was performed. Ex vivo drug uptake was evaluated by using a Franz diffusion cell. RESULTS: Thiolated ß-CDs presented 1804.68 ± 25 µmol/g thiol groups and 902.34 ± 25 µmol/g disulfide bonds. Nanoparticles displayed particle sizes within a range of 231 ± 07 nm to 354 ± 13 nm. The zeta potential was in the range of -8.1 ± 02 mV, +16.0 ± 05 mV. FTIR analyses confirmed no interaction between the excipients and drug. Delayed drug release was observed from Thio-NP. Thio-NP retained over hair surfaces for a significantly longer time. Similarly, drug retention was significantly improved. Thio-NP displayed no irritation over rabbit skin. CONCLUSION: Owing to the above results, nanoparticles developed with MXD-loaded thiolated ß-CDs might be a potential drug delivery system for topical scalp diseases.

Mucoadhesive, Fluconazole-Loaded Nanogels Complexed with Sulfhydryl-ß-cyclodextrin for Oral Thrush Treatment.

The objective of this study was to generate fluconazole-loaded mucoadhesive nanogels to address the problem of hydrophobicity of fluconazole (FL). An inclusion complex was formulated with sulfhydryl-ß-CD (SH-ß-CD) followed by nanogels formation by a Schiff base reaction of carbopol 940 (CA-940) and gelatin (GE). For characterization, PXRD, FT-IR analysis, drug content, and phase solubility studies were performed. Similarly, nanogels were assessed for particle size, zeta potential, organoleptic, and spreadability studies. Moreover, drug contents, rheological, in vitro drug permeation, release kinetics, toxicity, and stability studies of nanogels were performed. Furthermore, mucoadhesive characteristics over the buccal mucosal membrane of the goat were evaluated. The nanogels formulated with a higher amount of CA-940 and subsequently loaded with the inclusion complexes of FL showed promising results. PXRD and FT-IR analysis confirmed the physical complexes by displaying a reduction in the intensity of peaks of FL. The average particle size of nanogels was in the range of 257 to 361 nm. The highest drug content of 88% was encapsulated within the FL-SH-ß-CD complex. All formulations at 0.5-1% concentration displayed no toxicity to the Caco-2 cell lines. Nanogels loaded with FL-SH-ß-CD complexes showed 18-fold improved mucoadhesion on the buccal mucous membrane of the goat when compared to simple nanogels. The in vitro permeation study exhibited significantly enhanced permeation and first-order concentration-dependent drug release was observed. On the bases of these findings, we can conclude that a mucoadhesive nanogel-based drug delivery system can be an ideal therapy for candidiasis.

Enhanced Intestinal Permeability of Cefixime by Self-Emulsifying Drug Delivery System: In-Vitro and Ex-Vivo Characterization.

BACKGROUND: Cefixime (CFX) belongs to a group of third-generation cephalosporin antibiotics with low water solubility and low intestinal permeability, which ultimately leads to significantly low bioavailability. AIM: This study aimed to increase solubility, improve drug release, and intestinal permeability of CFX by loading into SEDDS. METHODS: Suitable excipients were selected based on drug solubility, percent transmittance, and emulsification efficiency. Pseudo-ternary phase diagram was fabricated for the identification of effective self-emulsification region. The best probably optimized formulations were further assessed for encumbered drug contents, emulsification time, cloud point measurement, robustness to dilution, mean droplet size, zeta potential, polydispersity index (PDI), and thermodynamic and chemical stability. Moreover, in vitro drug release studies and ex vivo permeation studies were carried out and apparent drug permeability Papp of different formulations was compared with the marketed brands of CFX. RESULTS: Amongst the four tested SEDDS formulations, F-2 formulation exhibited the highest drug loading of 96.32%, emulsification time of 40.37 ± 3 s, mean droplet size of 19.01 ± 1.12 nm, and demonstrated improved long-term thermodynamic and chemical stability when stored at 4 °C. Release studies revealed a drug release of 97.32 ± 4.82% within 60 min in simulated gastric fluid. Similarly, 97.12 ± 5.02% release of CFX was observed in simulated intestinal fluid within 120 min; however, 85.13 ± 3.23% release of CFX was observed from the marketed product. Ex vivo permeation studies displayed a 2.7-fold increase apparent permeability compared to the marketed product in 5 h. CONCLUSION: Owing to the significantly improved drug solubility, in vitro release and better antibacterial activity, it can be assumed that CFX-loaded SEDDS might lead to an increased bioavailability and antibacterial activity, possibly leading to improved therapeutic effectiveness.

In-depth drug delivery to tumoral soft tissues via pH responsive hydrogel.

A pH responsive nanoparticle-hydrogel hybrid drug delivery system was investigated for in-depth anticancer drug delivery to solid tumours. It consists of acid susceptible polymer nanoparticles loaded in a chitosan hydrogel. The hybrid formulation was characterized by UV-visible spectroscopy, FTIR, SEM, TEM, particle size analysis, zeta potential measurement and viscosity measurement. Drug encapsulation and nanoparticle loading efficiencies were found to be 48% and 72% respectively which describes the efficient interaction of the chemical entities in this hybrid drug delivery system. The hydrogel exhibited pH responsive behaviour: minimal drug and nanoparticle release at physiological pH but an increase in viscosity under acidic conditions and fast nanoparticle and drug release. The cytotoxicity of the drug loaded hydrogel was investigated against the MCF-7 breast cancer cell line along with the drug and nanoparticles without hydrogel. The drug loaded hydrogel showed a better cytotoxic effect on MCF-7 cancer cells. Thus, drug loaded nanoparticles containing hydrogel could be a better option for maximum drug distribution in tumours.

Nano-Formulation Based Intravesical Drug Delivery Systems: An Overview of Versatile Approaches to Improve Urinary Bladder Diseases.

Intravesical drug delivery is a direct drug delivery approach for the treatment of various bladder diseases. The human urinary bladder has distinctive anatomy, making it an effective barrier against any toxic agent seeking entry into the bloodstream. This screening function of the bladder derives from the structure of the urothelium, which acts as a semi-permeable barrier. However, various diseases related to the urinary bladder, such as hyperactive bladder syndrome, interstitial cystitis, cancer, urinary obstructions, or urinary tract infections, can alter the bladder's natural function. Consequently, the intravesical route of drug delivery can effectively treat such diseases as it offers site-specific drug action with minimum side effects. Intravesical drug delivery is the direct instillation of medicinal drugs into the urinary bladder via a urethral catheter. However, there are some limitations to this method of drug delivery, including the risk of washout of the therapeutic agents with frequent urination. Moreover, due to the limited permeability of the urinary bladder walls, the therapeutic agents are diluted before the process of permeation, and consequently, their efficiency is compromised. Therefore, various types of nanomaterial-based delivery systems are being employed in intravesical drug delivery to enhance the drug penetration and retention at the targeted site. This review article covers the various nanomaterials used for intravesical drug delivery and future aspects of these nanomaterials for intravesical drug delivery.

Safety and Pharmaceutical Evaluation of a Novel Natural Polymer, Ocicum, as Solubility and Dissolution Enhancer in Solid Dispersion.

Plant mucilages are commonly employed as excipients in pharmaceutical manufacturing. Ocimum basilicum (Lamiaceae family), a source of hydrophilic mucilage referred herein as Ocicum, was evaluated for the solubility enhancer of a model drug, aceclofenac, in solid dispersions prepared using different methods. Polymer was extracted from O. basilicum and solid dispersions of aceclofenac were fabricated with Ocicum or Poloxamer 407 using polymer-to-drug ratios of 1:1, 1:2 and 1:3 utilizing solvent evaporation, lyophilization and melt methods. Ocicum was evaluated for its safety via acute toxicity study including different biochemical and hematological parameters including liver and kidney profiles. Moreover, different characterization studies including melting-point, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and differential thermal analysis (TGA) were used for evaluation of polymer and solid dispersions. Furthermore, solubility and dissolution studies were performed to confirm solubility enhancement. Ocicum was found to be safer, and different characterization studies confirmed the purity of the compounds. In addition, Ocicum exhibited up to 6.27-fold enhanced solubility as compared to pure aceclofenac; similarly, 4.51-fold increased solubility by the synthetic polymer in their respective solid dispersions was shown. Furthermore, Ocicum-based solid dispersions showed substantial improvement in dissolution of aceclofenac. Therefore, it can be concluded from the above-mentioned results that Ocicum might be used as an economical natural oral delivery carrier alternative to the synthetic polymers.

Antihypertensive and Vasorelaxant Effects of Citrus aurantifolia Linn. Fruit: Proposed Mechanisms.

Background: Citrus aurantifolia Linn. fruit, a natural dietary item, has long been used traditionally to treat hypertension in Pakistan. The current research work aims to explore the effect on blood pressure and its mechanisms. Methods: The aqueous methanol extract of plant fruit was used to evaluate hypotensive/antihypertensive, vasorelaxation, and safety profiles. Moreover, the in vitro inhibitory effect of AMECA on phosphodiesterase was also evaluated. Results: In hypotensive studies, extracts of Citrus aurantifolia fruit exhibited a concentration-dependent reduction in SBP, DBP, MAP, and heart rate. A similar effect has been observed on anesthetized rats, but the effects exerted by the extract were not altered significantly in the presence of L-NAME, atropine, captopril, and propranolol. Moreover, in coronary arteries, the extract significantly potentiated relaxations induced by cGMP- and cAMP-dependent relaxing agonists. When exposed to PDEs, the extract concentration dependently subdued cGMP-hydrolyzing activity of different PDEs with IC50 values of 40-130 µg/mL. Conclusion: It is conceivable that extracts obtained from Citrus aurantifolia fruit produced hypotensive and antihypertensive effects in rats. The extract elicited endothelium-independent vasorelaxation, possibly by acting directly on smooth muscles of the coronary artery and by increasing cGMP and cAMP via nonselective inhibition of vascular PDEs.

Protective Effect of Butanolic Fraction of Delphinium brunonianum on Fructose-Mediated Metabolic Alterations in Rats.

The present study was conducted with an intent to evaluate the protective effect of butanolic fraction of Delphinium brunonianum on fructose mediated metabolic abnormalities in rats. Rats in all groups except control group were fed on 10% fructose for 6 weeks; however, rats in the treated group also received butanolic fraction for the last 3 weeks, along with the fructose. Moreover, phytoconstituents present in butanolic fraction were analyzed using LC-MS. All doses of butanolic fraction profoundly reduce the fructose-induced blood pressure, sympathetic over-activity, and weight gain. Furthermore, butanolic fraction prominently reduces the glucose intolerance and hyperinsulinemia in fructose-fed rats. On treatment with butanolic fraction, oxidative enzymes and the functionality of the aorta was also restored. Phytochemical analysis revealed the presence of several active constituents including bergenin, scopolin, rutinoside, kaempferol, coumaric acid, apigenin, and gingerol. In conclusion, butanolic fraction of Delphinium brunonianum has the potential to prevent and recover the fructose-induced metabolic perturbations.

Ex vivo, in vitro, and in silico approaches to unveil the mechanisms underlying vasorelaxation effect of Mentha Longifolia (L.) in porcine coronary artery.

OBJECTIVE: Mentha (M.) longifolia (L.) is traditionally used for various ailments. The current study was intended to explore the underlying vasorelaxation mechanisms of M. longifolia. MATERIAL AND METHODS: Aqueous-methanol extract from the aerial parts of M. longifolia was prepared and subjected to activity-guided fractionation. The vasorelaxant activity was performed using porcine coronary arteries with intact and denuded endothelium. In-vitro PDE inhibitory activity of the active fraction was carried out using the radio-enzymatic assay. The active fraction was also subjected to GCMS. Docking and molecular dynamic simulation studies were also performed RESULT: We had observed that aqueous-methanolic extract induced relaxation in the coronary artery in a dose-dependent manner when the endothelium was intact and denuded. n-butanol fraction (MLB) has produced a maximum effect, and it was selected for mechanistic studies. MLB has significantly enhanced the relaxation produced by cAMP and cGMP, elevating atrial natriuretic peptide, sodium nitroprusside, isoproterenol, and forskolin. The pre-treatment with MLB inhibited the contractile response produced by KCl, U46619, and CaCl2 in without endothelium rings. MLB has non-selectively inhibited the PDE isoforms. GCMS analysis of MLB has revealed the presence of menthol, thymol, and carvacrol in the active fraction. Docking and molecular dynamic simulation studies have indicated that thymol can be a competitive inhibitor for PDE1. CONCLUSION: It is postulated that an n-butanol fraction of Mentha longifolia produced endothelium-independent relaxation due to increased levels of cAMP and cGMP caused by the inhibition of various PDEs.

Reduction of Hepatic Steatosis, Oxidative Stress, Inflammation, Ballooning and Insulin Resistance After Therapy with Safranal in NAFLD Animal Model: A New Approach.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is intimately linked to hepatic steatosis, inflammation, insulin resistance (IR), oxidative stress (OS), and ballooning. A high fat diet (HFD) is considered a major etiological factor that primarily covers the numerous features of NAFLD. METHODS: The present study aimed to evaluate the protective effect of safranal on hepatic steatosis, OS, liver index, IR index, liver function enzymes, plasma lipids, TNF-α, malondialdehyde (MDA), advanced oxidation protein products (AOPPs) and nitrite (NO2 -) levels in a NAFLD rat model fed with a HFD for 12 weeks. The ELISA kits were used to measure TNF-α and insulin in serum and plasma, respectively. RESULTS: HFD significantly induced hepatic steatosis, OS, IR, liver, and oxidative enzyme elevation and inflammation in experimental animals. Rats treated with safranal in ascending order of doses 250 and 500 mg/kg orally for 4-weeks showed a reduction in hepatic lipid's accumulation, liver index, hepatic enzymes, collagen, hepatic oxidonitrative stress markers (like AOPP, MDA and NO2 -), and raised the levels of catalase (CAT) and superoxide dismutase (SOD) enzymes. Glutathione system components, namely glutathione (GSH), glutathione peroxidase (GPx), and glutathione-S-transferase (GST) levels were also restored in the safranal-treated groups. The reduction in serum TNF-α and IR provided further support to the anti-NAFLD effect of safranal. Moreover, the histopathological images indicated reverse of NAFLD activity score (NAS) through mild fatty degeneration, ballooning and inflammation in hepatocytes of treated groups. CONCLUSION: Findings of blood and tissue analysis concluded that safranal can be a good choice in the management and cure of NAFLD.

Thiolated pectins: In vitro and ex vivo evaluation of three generations of thiomers.

In recent decades, three generations of thiomers have been developed with the main purpose of obtaining enhanced interactions with mucosal tissues. Therefore, many different types of thiolated ligands have been generated and attached to polymeric backbones. The aim of this study was to synthesize all three generations of thiomers and to directly compare their properties regarding mucus penetration and mucoadhesion. Starting from pectin, the unprotected thiomer pectin-cysteine (Pec-Cys), the preactivated S-protected thiomer pectin-cysteine-mercaptonicotinic acid (Pec-Cys-MNA) and the less reactive S-protected thiomer pectin-cysteine-glutathione (Pec-Cys-GSH) were synthesized and characterised by FT-IR, NMR, and colorimetric studies. The polymers were evaluated regarding their cytotoxicity, swelling behaviour, viscosity after mixing with mucus, mucus diffusion, penetration into mucosa, and mucoadhesion. The amount of the three ligands (Cys, Cys-MNA and Cys-GSH) bound to the polymer was determined to be in the range of 193-196 µmol/g. All polymers showed no cytotoxicity. Viscosity of the mixture of Pec-Cys-MNA and Pec-Cys-GSH with mucus increased 21.5- and 26.7-fold, respectively, compared to the unmodified polymer within 3 hours. Swelling, mucoadhesion, interpenetration and mucus diffusion were increased in the following rank order: Pec-Cys < Pec-Cys-MNA < Pec-Cys-GSH. Results of mucoadhesion study indicated a 7.4 and 8.1-fold increase of Pec-Cys-MNA and Pec-Cys-GSH, respectively, compared to the unmodified polymer. As the less reactive S-protected thiomer exhibited higher mucoadhesive properties than the other thiomers, this study provides evidence for the superior mucoadhesion of 3rd generation thiomers. STATEMENT OF SIGNIFICANCE: Three generations of thiolated polymers have been developed bearing different types of thiol ligands with the main purpose of enhancing mucus interactions. In this study, all generations were synthesized on the polymeric backbone of pectin for the first time to directly compare their mucus penetrating and mucoadhesive properties. 1st generation exhibited covalently bound L-cysteine moieties. For 2nd generation, thiols of cysteines were S-protected with 2-mercaptonicotinic acid (MNA), resulting in high reactive disulfide bonds. 3rd generation was synthesized by a thiol/disulfide exchange of glutathione with MNA, producing a less reactive disulfide bond. Mucus penetrating and mucoadhesive properties were found to be increased as follows: 1st generation < 2nd generation < 3rd generation. According to these results, the thiomer of 3rd generation represents a promising excipient with strong mucoadhesion.

RETRACTED: Potential of ephedrine to suppress the gene expression of TNF-α, IL-1ß, IL-6 and PGE2: A novel approach towards management of rheumatoid arthritis.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. A reader reported that Figure 9 of the above paper contains similar section with Figure 4 of another article authored by the same group in Inflammopharmacology, 29, (2021) 1119-1129, https://doi.org/10.1007/s10787-021-00840-9, and part of the Figure 9 of the above paper is used in Figure 9 of another article authored by the same group in Inflammopharmacology, 29, (2021) 673­682, https://doi.org/10.1007/s10787-021-00804-z. The journal requested the authors to explain the repeated use of the image and provide the raw data. However, the authors were not able to fulfill this request and therefore the Editor-in-Chief has decided to retract the article.

Impact of pharmacist-led interventions in improving adherence to glaucoma medications in the geriatric population.

OBJECTIVES: Geriatric patients can be non-adherent to ophthalmic glaucoma medications because of complex eye drops instillation techniques and forgetfulness, so pharmacists can play their part in improving the clinical outcomes of patients by acting as care providers. The purpose of the current study was to implement various pharmacist-led interventions to improve adherence to glaucoma medications and to evaluate the outcomes of interventions in the geriatric population. METHODS: The Morisky Green Levine (MGL) adherence scale was used for analysis because it measures the extent of non-adherence and analyses the reasons for it. The interview-based sessions were conducted with control and interventional groups followed by educational interventions, including techniques for eye drop instillation, graphical images, precautionary measures, and individual patient counselling for the interventional group. Patients were asked to complete the adherence scale after the conclusion of every follow-up session for a duration of 6 months. RESULTS: After 6 months of pharmacist-led interventions, a significant shift was found in the interventional group from low to high adherence according to MGL scale evaluation. Moreover, the number of patients in the interventional group whose intraocular pressure was in the safe range significantly increased and follow-up sessions significantly improved the patient's knowledge about glaucoma. CONCLUSION: The results of this pharmacist-led educational interventional study showed it was effective in improving adherence to glaucoma medications in the geriatric patients, who showed better adherence scores and improved intraocular pressure.

Venlafaxine demonstrated anti-arthritic activity possibly through down regulation of TNF-α, IL-6, IL-1ß, and COX-2.

Venlafaxine is a serotonin-norepinephrine reuptake inhibitor used to treat depression. Previous studies demonstrated its anti-nociceptive and anti-inflammatory activities through the suppression of pro-inflammatory cytokines. Present research aimed to explore its anti-arthritic potential. Different in-vitro assays including egg albumin, bovine serum albumin denaturation and human red blood cell (RBC) membrane stabilization assays along with in-vivo models of formaldehyde and complete Freund's adjuvant-induced arthritis were used to study its anti-arthritic effect. Venlafaxine inhibited egg albumin and bovine serum albumin denaturation and preserve the integrity of red blood cells membrane in concentration-dependent manner. In formaldehyde-induced arthritis venlafaxine significantly (p < 0.001) reduced the paw edema on treatment for 10 days. Chronic administration of venlafaxine for 28 days in Freund's adjuvant-induced arthritis model decreased the paw volume (p < 0.001), arthritic index (p < 0.01), flexion pain score (p < 0.05), mobility score (p < 0.05), and improved the stance score (p < 0.05). Venlafaxine also significantly declined the rheumatoid factor (p < 0.01) and C-reactive protein (p < 0.05) levels and increased the RBC count (p < 0.01) and Hb value (p < 0.001). Upon PCR analysis venlafaxine remarkably turndown the mRNA expression of TNF-α, IL-6, IL-1ß, and COX-2. Taken together it is inferred from current findings that venlafaxine possesses the significant anti-arthritic activity and could be a potential therapeutic option for the treatment of rheumatoid arthritis.

Anti-rheumatic activity of pseudoephedrine (a substituted phenethylamine) in complete Freund's adjuvant-induced arthritic rats by down regulating IL-1ß, IL-6 and TNF-α as well as upregulating IL-4 and IL-10.

Pseudoephedrine (substituted phenethylamine) is well known as psychotic and bronchodilator. Numerous studies on phenethylamine derivatives indicated that these agents have the potential to abolish inflammatory responses in the non-biological and biological systems. These facts provided the basis to conduct a study on pseudoephedrine to explore its therapeutics in Complete Freund's Adjuvant (CFA)-induced arthritis. Furthermore, existing treatment approaches for RA associated with limited effect on chronic immunological models. Real-time polymerase chain reaction (q-PCR) was performed to execute the expression of pro and anti-inflammatory cytokines in treated and non-treated arthritic rats. These findings were further co investigate by histological observations. The paw volume, paw diameter, weight variations and arthritic score were determined at specific days throughout the experiment of 28 days. Pseudoephedrine at all doses significantly (p < 0.001) suppressed the expression of PGE2, TNF-α, IL-1ß and IL-6. Moreover, pseudoephedrine (20 and 40 mg/kg) caused significant augmentation of IL-4 and IL-10. Similarly, the drug expressed a significant anti-arthritic effect by reducing the paw volume, paw diameter and arthritic score. Similarly, it also reverts the reduction in body weight of arthritic rats at all above-mentioned doses. These findings supported the anti-arthritic potential of pseudoephedrine and recommended it for clinical trials.

Thiolated cyclodextrins: Mucoadhesive and permeation enhancing excipients for ocular drug delivery.

Thiolated ß-cyclodextrin (ß-CD) has the potential to enhance mucoadhesive and permeation enhancing properties on ocular mucosa. Thiolated ß-CD was synthesized via replacement of all primary hydroxyl groups on ß-CD backbone by halogen followed by substitution with thiol groups. The structure was confirmed by FT-IR and 1H NMR spectroscopy. Thiolated CD was characterized for hemolytic effect, ocular irritation, solubility enhancement, viscoelastic behavior and mucoadhesive properties. Moreover, the permeation enhancing effect of thiolated oligomer on different ocular tissues including conjunctiva, sclera and cornea was evaluated with sodium fluorescein (Na-Flu) as a marker. Thiolated ß-CD displayed 5360 ± 412 µmol/g thiol groups. The newly synthesized oligomer did not show any hemolytic effect on red blood cells at a concentration of 0.5% (m/v) for an incubation period of 3 h and minimal corneal irritation effects without any inflammation within 72 h. Thiolated ß-CD exhibited a 5.3-fold improved aqueous solubility as compared to the unmodified ß-CD. Thiolated oligomer (0.5% m/v) enhanced the viscosity of mucus up to 6.2-fold within 4 h and provided a 26-fold prolonged ocular residence time due to mucoadhesion. Moreover, 0.5% (m/v) thiolated ß-CD enhanced the permeation of Na-Flu 9.6-, 7.1- and 5.3-fold on conjunctiva, sclera and cornea, respectively. Based on these findings, thiolated ß-CD might be a promising auxiliary agent for ocular drug delivery.

Zeta potential changing nanoemulsions based on a simple zwitterion.

HYPOTHESIS: Simple zwitterions used as auxiliary agents might have the potential to change the zeta potential of oil-in-water (o/w) nanoemulsions on the mucosa. EXPERIMENTS: The zwitterion phosphorylated tyramine (p-Tyr) was synthesized by phosphorylation of Boc-tyramine (Boc-Tyr) using phosphoryl chloride (POCl3). It was incorporated with 2% (m/v) in a self-emulsifying lipophilic phase comprising Captex 35, Cremophor EL, Capmul MCM and glycerol 85 at a ratio of 30:30:30:10 v/v. Phosphate release and resulting change in zeta potential were evaluated by incubating p-Tyr containing nanoemulsion with isolated intestinal alkaline phosphatase (AP). Mucus permeating behavior was evaluated across mucus obtained from porcine small intestinal mucosa. Subsequently, cellular uptake studies were accomplished on Caco-2 cells. FINDINGS: The p-Tyr loaded nanoemulsion exhibited a mean droplet size of 43 ± 1.7 nm and zeta potential of -8.40 mV. Phosphate moieties were rapidly cleaved from p-Tyr loaded nanoemulsions after incubation with isolated AP resulting in a shift in zeta potential from -8.40 mV to +1.2 mV. p-Tyr loaded nanoemulsion revealed a significantly (p ≤ 0.001) improved mucus permeation compared to the same nanoemulsion having been pre-treated with AP. Cellular uptake of the zeta potential changing oily droplets was 2.4-fold improved. Phosphorylated zwitterions seem to be an alternative to cationic surfactants and considered as promising auxiliary agents for zeta potential changing nanoemulsions.

Anti-Proliferative and Apoptosis-Inducing Activity of Acacia Modesta and Opuntia Monocantha Extracts on HeLa Cells.

BACKGROUND: Cancer is one of the leading causes of death in the world. Numerous phytochemicals from plants have shown antineoplastic effects via programmed cell death (apoptosis). The aim of this study was to evaluate the effect of anti-proliferative and apoptosis-inducing activity of Acacia modesta and Opuntia monocantha against HeLa cells. METHODS: To estimate anti-proliferative activity of the plants against HeLa cells, ethanol solvent was used for the extraction. For the evaluation of anti-proliferative effects, MTT assay was performed with 100, 200, and 400 µg/mL dose. The antioxidant assays including glutathione reductase (GSH), superoxide dismutase (SOD) and catalase were performed. Moreover, enzyme linked immunosorbent assay (ELISA) was performed. Furthermore, immunocytometry P53 and flow cytometry were also carried out to assess the apoptosis in HeLa cell. RESULTS: MTT assay showed that the groups treated with Opuntia monocantha and Acacia modest have less level of toxicity as compared to untreated groups. Antioxidant assays confirmed that GSH, SPD and, catalase activities were quite decreased in treated groups as compared to untreated groups. Similarly, ELISA and apoptosis p53 have shown more pronounced apoptosis effect in treated groups as compared to untreated groups. CONCLUSION: Based on above findings, treatment of HeLa cells with these plant extracts induced apoptosis, restricts proliferation, and enhances the anti-oxidative index in post treated cells.
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