Magnetic nanoparticles that are currently explored for various biomedical applications exhibit a high propensity to minimize total surface energy through aggregation. This study introduces a unique, thermoresponsive nanocomposite design demonstrating substantial colloidal stability of superparamagnetic Fe3O4 nanoparticles (SPIONs) due to a surface-immobilized lipid layer. Lipid coating was accomplished in different buffer systems, pH 7.4, using an equimolar mixture of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and L-α-dipalmitoyl-phosphatidyl glycerol (DPPG). Particle size and zeta potential were measured by dynamic laser light scattering. Heating behavior within an alternating magnetic field was compared between the commercial MFG-1000 magnetic field generator at 7 mT (1 MHz) and an experimental, laboratory-made magnetic hyperthermia system at 16.6 mT (13.7 MHz). The results revealed that product quality of lipid-coated SPIONs was significantly dependent on the colloidal stability of uncoated SPIONs during the coating process. Greatest stability was achieved at 0.02 mg/mL in citrate buffer (mean diameter = 80.0 ± 1.7 nm; zeta potential = −47.1 ± 2.6 mV). Surface immobilization of an equimolar DPPC/DPPG layer effectively reduced the impact of buffer components on particle aggregation. Most stable suspensions of lipid-coated nanoparticles were obtained at 0.02 mg/mL in citrate buffer (mean diameter = 179.3 ± 13.9 nm; zeta potential = −19.1 ± 2.3 mV). The configuration of the magnetic field generator significantly affected the heating properties of fabricated SPIONs. Heating rates of uncoated nanoparticles were substantially dependent on buffer composition but less influenced by particle concentration. In contrast, thermal behavior of lipid-coated nanoparticles within an alternating magnetic field was less influenced by suspension vehicle but dramatically more sensitive to particle concentration. These results underline the advantages of lipid-coated SPIONs on colloidal stability without compromising magnetically induced hyperthermia properties. Since phospholipids are biocompatible, these unique lipid-coated Fe3O4 nanoparticles offer exciting opportunities as thermoresponsive drug delivery carriers for targeted, stimulus-induced therapeutic interventions.

Objectives: The purpose of this study was to formulate and characterize metoclopramide solid lipid nanoparticles (MCP-SLNs) and incorporating it into suppository bases for treatment of nausea and vomiting, produced with chemotherapeutic agents, using one dose per day. Methods: MCP-SLNs was prepared using high shear homogenization (hot homogenization) technique using different surfactants (tween 80, poloxamer 407, poloxamer 188 and cremophore) in two different concentrations (2.5% and 5%) then solid lipid nanoparticle (SLN), whose release percentage above 50%, was incorporated into suppository for treatment of nausea and vomiting. The prepared SLN and suppositories were then evaluated and characterized. Key findings: Formulation of poloxamer 407 with compritol and drug (F9) produced highest in-vitro % release (80%). Transmission electron microscopy showed that SLN had round and spherical shape in form of solid dispersion or drug-enriched core. Particle size analysis of SLN showed a size range of 24.99–396.8 nm. Negative zeta potential proves complete drug entrapment. In-vivo study of MCP-SLN suppositories produced the same %GE as the market metoclopramide (MCP) suppository (Primperan) with sustained release effect. Conclusion: MCP-SLN suppositories (formula F) can reverse decrease in %GE because of emesis with sustained release effect. So it succeeded to be an alternative to MCP suppositories with no multiple dosing.

Betamethasone sodium phosphate is a potent glucocorticoid with anti-inflammatory activity and can be used in treatment of macular edema. The aim of this work is to formulate and investigate mucoadhesive chitosan-sodium alginate nanoparticles as new vehicle for the prolonged topical ophthalmic delivery of betamethasone sodium phosphate. Ionotropic gelation method was used to produce betamethasone loaded chitosan alginate nanoreservoir system. The effect of changing different formulation parameters (pH of chitosan solution, sodium alginate concentration, calcium chloride concentration, chitosan concentration, drug concentration and the addition of tween 80) on the physicochemical properties and in-vitro release of the drug loaded nanoparticles was studied. The mean particle size ranged from 16.8 to 692 nm and the zeta potential generally ranged from +18.49 to +29.83 mV depending on the formulation conditions. The highest encapsulating efficiency obtained was 64%. In-vitro release studies showed an initial burst release of the drug followed by slow sustained release over 24, 48 or 72 hours depending on the formulation parameters. The in-vivo studies carried out for two selected formulations showed the release of 84%, 59.5% of the drug over 12 hours for both F3C and F12 respectively. The results of physicochemical properties of F3C and F12 upon storage showed good stability at both 25°C and 40°C as the drug content was within the accepted range, the pH was (5–7) and the mean particle size for both formulations over the three months was still interesting for ophthalmic application. The results of this study suggest that chitosan alginate nanoparticles would be a promising system for the sustained release delivery of betamethasone sodium phosphate to the posterior segment of the eye.

The present work focuses on treatment of glaucoma by formulating ocular inserts of different polymeric combination and Timolol maleate to enhance therapeutic effect through prolonging contact time with corneal surface, accurate, and sustain the release of the drug over a long period. The selected polymers for formulation of ocular inserts are Methyl Cellulose (MC), Hydroxypropyl cellulose (HPC), Eudragit RL100 (ERL100), Eudragit RS100 (ERS100), Ethylcellulose (EC), Polyvinylpyrrolidone (PVP). Films were plasticized using different plasticizers. The prepared ocular inserts were evaluated for their mechanical properties and physico-chemical properties. Accelerated stability studies were conducted to investigate the change in appearance, pH, and drug content after storage in drastic conditions. In-vitro drug release and kinetics of drug release from different formulations were studied. In-vitro permeation study was conducted on selected formulations showed better results in previous studies. In-vivo release study was conducted on rabbits after sterilization of ocular inserts by gamma radiation. Intraocular pressure was measured at different time intervals using Schotz tonometer. The in-vitro release data of Timolol maleate from the prepared formulations followed diffusion mechanism. The permeability studies data revealed that the permeability coefficient was found to be dependent on polymer type, the higher the solubility of the polymer the higher permeability coefficient. The reduction in IOP for F3 (HPC/ERL100 5:1), F7 (MC/ERL100 1:1), and F8 (MC/ERL100 1:3) was prolonged for 120 hours (5 days), and 96 hours (4 days) for F12 (HPC/EC 15:1).

The present work describes the synthesis and evaluation of some new acetohydrazones, 1,3,4-oxadiazoles and 1,2,4-triazoles of 1,2,4-triazolo[1,5-a]benzimidazole as anti-inflammatory-analgesic agents. Structure elucidation of these compounds was confirmed by IR, 1H NMR, and mass spectrometry along with elemental microanalyses. Most compounds exhibited significant anti-inflammatory activity in comparison to indomethacin. Further, some compounds were tested for their analgesic effects where two compounds showed results comparable to indomethacin at 4 h interval. The most active anti-inflammatory and analgesic compounds (4c and 11a) were examined on gastric mucosa and didn’t show any gastric ulcerogenic effect compared with the reference indomethacin. Moreover, LD50 of compounds (4c and 11a) were determined in mice; they were found non toxic up to 240 and 300 mg/kg (i.p.). Also, docking simulation of some compounds into COX active sites was studied.

The present work describes the synthesis and evaluation of some new acetohydrazones, 1,3,4-oxadiazoles and 1,2,4-triazoles of 1,2,4-triazolo[1,5-a]benzimidazole as anti-inflammatory-analgesic agents. Structure elucidation of these compounds was confirmed by IR, 1H NMR, and mass spectrometry along with elemental microanalyses. Most compounds exhibited significant anti-inflammatory activity in comparison to indomethacin. Further, some compounds were tested for their analgesic effects where two compounds showed results comparable to indomethacin at 4 h interval. The most active anti-inflammatory and analgesic compounds (4c and 11a) were examined on gastric mucosa and didn’t show any gastric ulcerogenic effect compared with the reference indomethacin. Moreover, LD50 of compounds (4c and 11a) were determined in mice; they were found non toxic up to 240 and 300 mg/kg (i.p.). Also, docking simulation of some compounds into COX active sites was studied.

The present work describes the synthesis and evaluation of some new acetohydrazones, 1,3,4-oxadiazoles and 1,2,4-triazoles of 1,2,4-triazolo[1,5-a]benzimidazole as anti-inflammatory-analgesic agents. Structure elucidation of these compounds was confirmed by IR, 1H NMR, and mass spectrometry along with elemental microanalyses. Most compounds exhibited significant anti-inflammatory activity in comparison to indomethacin. Further, some compounds were tested for their analgesic effects where two compounds showed results comparable to indomethacin at 4 h interval. The most active anti-inflammatory and analgesic compounds (4c and 11a) were examined on gastric mucosa and didn’t show any gastric ulcerogenic effect compared with the reference indomethacin. Moreover, LD50 of compounds (4c and 11a) were determined in mice; they were found non toxic up to 240 and 300 mg/kg (i.p.). Also, docking simulation of some compounds into COX active sites was studied.

Two novel microwell-based spectrophotometric methods with high throughput have been developed and validated for the determination of ciprofloxacin (CIP), a fluoroquinolone antimicrobial agent. These methods were based on the formation of colored condensation products upon reaction of CIP with each of 1,2-naphthoquinone-4-sulphonic acid sodium salt (NQS) and the oxidized pyrocatechol (OPC). These reactions were carried out in a 96-microwell plate and the absorbance of the colored-product was measured by a microwell plate absorbance reader at 460 and 510 nm for NQS and OPC, respectively. The variables affecting the reactions were carefully investigated and the conditions were optimized. The stoichiometry of the reaction was determined, and the reactions pathways were postulated. The proposed reactions were found to be highly selective for CIP among many fluoroquinolone members. Under the optimum conditions, good linear relationships were obtained between the absorbances and the concentrations of CIP in the ranges of 25–200 and 40–450 μg/mL with limits of detections of 3.66 and 8.79 mg/mL for the methods based on NQS and OPC, respectively. The robustness and ruggedness of the methods were satisfactory. The methods were successfully applied to the bulk drug and pharmaceutical dosage forms; the percentage recoveries were 98.0-101.5 (0.45 ± 1.63%). The results were compared favorably with those obtained by a pre-validated reference method; no significant difference in accuracy and precision as revealed by the accepted values of t– and F–tests, respectively.

Two novel microwell-based spectrophotometric methods with high throughput have been developed and validated for the determination of ciprofloxacin (CIP), a fluoroquinolone antimicrobial agent. These methods were based on the formation of colored condensation products upon reaction of CIP with each of 1,2-naphthoquinone-4-sulphonic acid sodium salt (NQS) and the oxidized pyrocatechol (OPC). These reactions were carried out in a 96-microwell plate and the absorbance of the colored-product was measured by a microwell plate absorbance reader at 460 and 510 nm for NQS and OPC, respectively. The variables affecting the reactions were carefully investigated and the conditions were optimized. The stoichiometry of the reaction was determined, and the reactions pathways were postulated. The proposed reactions were found to be highly selective for CIP among many fluoroquinolone members. Under the optimum conditions, good linear relationships were obtained between the absorbances and the concentrations of CIP in the ranges of 25–200 and 40–450 μg/mL with limits of detections of 3.66 and 8.79 mg/mL for the methods based on NQS and OPC, respectively. The robustness and ruggedness of the methods were satisfactory. The methods were successfully applied to the bulk drug and pharmaceutical dosage forms; the percentage recoveries were 98.0-101.5 (0.45 ± 1.63%). The results were compared favorably with those obtained by a pre-validated reference method; no significant difference in accuracy and precision as revealed by the accepted values of t– and F–tests, respectively.

The present study aims to investigate the possibility of interaction of donepezil (DP) and galantamine (GAL) as acetylcholinestrase inhibitors, on memantine (MT) hydrochloride in rat plasma by HPLC-fluorescence detection. The separation of MT was achieved within 12 min without interference of DP and GAL on the chromatogram. MT levels in rat plasma with a single administration of MT (2.5 mg/kg, i.p.) and those with a co-administration of DP (5.0 mg/kg, i.p.) and GAL (3 mg/kg, i.p.) were monitored. MT concentrations determined in rat plasma ranged from 10.0 to 245.6 ng/mL. Significant difference was observed in the behavior of MT with a co-administration of DP, while no significant difference was observed with a co-administration of GAL.