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Context: The application of soil amendments to immobilise pesticide residues is a promising technology for meeting human health requirements, environmental protection and cost-effective remediation. Aims: This study aims to evaluate the effect of rice straw biochar (RB), rice straw compost (RC) and their mixtures at rates of 0.5% and 1.0% in pots, on the immobilisation of pesticides (such as atrazine, glyphosate and chlorpyrifos) in contaminated soil, using spectroscopy analysis under grown canola (Brassica napus L.) plants. Methods: Determination of immobilisation of pesticide residues by GC or HPLC and chemical properties of RB and RC and adding them at differentrates to the contaminated soil. Keyresults: The results showed that the addition of RB or RC alone or their mixtures led to a significant increase in the exchangeable Ca2+ contents, organic matter (OM), cation exchange capacity (CEC), uptake of N, P and K and dry weight of canola plants. Pesticide concentrations decreased with increasing OM, CEC, and exchangeable Ca2+ with the soil amended by RC and RB. The data indicated that adding RB at levels of 0.5% and 1.0% resulted in reductions in chloropyrifos by 43.2% and 63.1%, glyphosate by 32.8% and 77.3%, and atrazine by 21.9% and 72.2%, respectively, as compared to the control. Addition of (RC + RB) at 0.5% gave the highest pesticide immobilisation, followed (RC+RB) at 1.0%. Conclusion: These results indicate that the dominant mechanisms of pesticides immobilisation in the alkaline soils amended with RC and RB by FTIR and XRD analysis were π–π interaction, pore filling, hydrophobic effect, H-bonding, degradation as well as improvement of soil properties and dry yield of canola plants. Implications: Our results suggested the possibility of adding recycled rice straw in the form of compost or biochar to the contaminated soil to improve its properties, immobilise pesticides and increase its production capacity. The application of soil amendments to immobilise pesticide residues is a promising technology for meeting human health requirements, environmental protection and cost-effective remediation. The addition of biochar with compost increased the canola growth and decreased the concentrations of pesticide residues. Spectroscopy analysis indicated that the π–π interaction, pore filling, hydrophobic effect, H-bonding, and degradation are the dominant mechanisms of the studied pesticide residues with rice straw of biochar and compost amendments in the alkaline soils. [ABSTRACT FROM AUTHOR]

Aya M Khallaf,1 Riham M El-Moslemany,1 Mahmoud F Ahmed,2 Mahmoud H Morsi,3 Nawal M Khalafallah1 1Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; 2Managing Director at Ultimate Pharma Company, Alexandria, Egypt; 3Department of Ophthalmology, Faculty of Medicine, Alexandria University, Alexandria, EgyptCorrespondence: Riham M El-MoslemanyDepartment of Pharmaceutics, Faculty of Pharmacy, Alexandria University, 1, Khartoum Square, Azarita, Alexandria, 21521, EgyptTel +20 1006020405Email riham.elmoslemany@alexu.edu.egPurpose: Fasudil hydrochloride (Fas), a rho-associated protein kinase inhibitor, proved to be promising for glaucoma management owing to its IOP lowering and antioxidant effects. However, its highly hydrophilic nature limits ocular permeation and bioavailability. Hence, the study objective was the development of Fas loaded vesicular system with high entrapment efficiency formulated as a thermosensitive gel for local administration aiming to enhance ocular retention and permeation and hence therapeutic efficacy.Methods: Fasudil complex with phospholipid (Fas/PL) was prepared by solvent evaporation technique and characterized by Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD). Fas/PL was further formulated as liposomes by methanol injection method and characterized regarding colloidal properties, entrapment efficiency (EE%) and in vitro drug release. The prepared liposomes were incorporated into an optimized thermosensitive in situ gel (Fas/PL-LipoP407/HPMCgel) selected based on gelling time and temperature and rheological properties. The effect of incorporation into gel on the in vitro characteristics of liposomes was investigated. The in vitro mucoadhesive potential, ex vivo permeation, irritability and efficacy in a glaucoma rabbit model were also assessed.Results: FT-IR and XRD suggested interactions between Fas and PL, proposing complexation. Fas/PL liposomal dispersions showed good colloidal properties (particle size: 132.5 ± 1.6 nm, zeta potential: − 21.6 ± 0.9 and %EE 78.6 ± 0.3%) with sustained drug release. In situ thermosensitive gel (20% poloxamer 407 and 0.5% HPMC) showed optimum gelling properties. The selected gel formulation reduced burst release of the drug, enhanced mucoadhesive properties and prolonged corneal permeation ex vivo. HET-CAM test confirmed that the prepared formulations were non-irritant. In vivo pharmacodynamic study indicated improved bioavailability and significantly lower intraocular pressure (IOP) of Fas/PL-LipoP407/HPMC gel compared to drug solution and liposomal dispersion.Conclusion: The results present Fas/PL-LipoP407/HPMC gel as a potential platform for ophthalmic delivery of fasudil with improved pharmaceutical attributes and enhanced bioavailability and efficacy in glaucoma.Keywords: fasudil hydrochloride, glaucoma, phospholipid-complex, liposomes, thermosensitive gel

Enrichment of calcareous soils with phosphogypsum and poultry manure amendments could increase nutrient availability, improve calcareous chemical characteristics, and enhance barley plant growth. In the current study, phosphogypsum (PG) and poultry manure (PM) were used to determine the effects of PG and PM application on soil fauna diversity, soil fertility, and barley yield. The pot experiment treatments were: C: control; PG1: 4.20 g kg -1 soil; PG2: 6.30 g kg -1 soil; PM1: 4.20 g kg -1 soil; PM: 6.30 g kg -1 soil, and their combinations. The results indicated that the application of PM alone or combined with PG had significant effects on the microbial biomass carbon (MBC), organic matter (OM), soil NPK availability, and yield of barley. Collembola and Prostigmata accounted for 50.0 and 43.3%, respectively, of the total number of soil fauna. Shannon and evenness indices increased significantly in the soil amended with PM alone or combined with PG. Amended soil with PG and/or PM significantly increased the yield and yield components of plants compared to the control. The PM1PG2 treatment increased the yield by 76.2% above the control., (© 2023. The Author(s).)

Background: In Egypt, calcareous soils represent a large part of desert soils suffering from a shortage of nutrients and organic matter, affecting production and biological diversity in agroecosystems. Organic wastes, negatively affect the environment, recycling it as a promising technology in different farming systems, and its impact on crop productivity and soil fauna is largely unknown. In this study, the effects of integrating poultry manure (PM) alone or combined with vinasse (V) at rates of 4.2 g kg - 1 and 6.3 g kg - 1 in pots, on improving soil fauna diversity, soil fertility, soil consistency and yield of barley (Hordeum aestivum L.) grown in a calcareous soil were investigated., Results: The results showed that the addition of PM alone or combined with V at different rates led to a significant increase in the microbial biomass carbon (MBC), organic matter (OM), NPK soil availability and yield of barley. The addition of 6.3 g PM and 4.2 g V kg - 1 soil have the best results in OM with 65.0% compared to control, and V contributes more than 16% of them. Prostigmata and Collembola were the dominant groups and accounted for 43.3% and 50.0% in the PM1 and 50.0% and 20.0% in the PM2 of the total individuals, respectively. Shannon and Evenness indices increased significantly with the soil amended by PM alone or combined with V. Soil fauna plays a key role in soil consistency because of a significant relationship between soil fauna and soil OM, MBC and soil fertility index. The addition of 6.3 g PM and 4.2 g V kg - 1 soil gave the best results in grain yield by 76.90% compared to the control., Conclusion: In conclusion, the interaction between PM and V can be used as a promising organic amendments to increase barley yield and improve efficiency of a recycled PM and V on soil fauna and soil fertility of calcareous soil., (© 2022. The Author(s).)

Photodynamic therapy (PDT) to manage non-melanoma skin cancers has garnered great attention over the past few years. Hypericin (Hy) is a potent lipid-soluble photosensitiser with promising anticancer therapeutic activities. Nevertheless, its poor water-solubility, aggregation in biological systems and insufficient skin penetration restricted its effective exploitation. Herein, we report for the first-time encapsulation of Hy into lipid nanocapsules (Hy-LNCs), and then application of an AdminPen™ hollow microneedles (Ho-MNs) array and an in-house fabricated Ho-MN to enable efficient intradermal delivery. The physicochemical properties, photoactivity, ex vivo drug distribution and cellular uptake were evaluated. Results showed that Hy-LNCs were successfully formed with a particle size of 47.76 ± 0.49 nm, PDI of 0.12 ± 0.02, high encapsulation efficiency (99.67% ± 0.35), 396 fold higher photoactivity, 7 fold higher skin drug deposition, significantly greater cellular uptake and higher photocytotoxicity compared to free Hy. The therapeutic effect of Hy-LNCs was finally assessed in vivo using a nude mouse model with transplanted tumours. Interestingly, Hy-LNCs delivered by Ho-MN exhibited remarkable anti-tumour destruction (85.84%) after irradiation with 595 nm. This study showed that Ho-MNs-driven delivery of Hy-LNCs followed by irradiation could form a promising minimally invasive, effective and site-specific approach for managing non-melanoma skin cancers., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Controversies surround levothyroxine sodium as a drug and product, and are reflected in compendia (USP vs BP) differences in levothyroxine sodium tablets specifications concerning potency limit and dissolution test conditions, and in lack of consensus on several issues such as whether the drug BCS class I or III. We have recently published a clinical study in patients comparing the efficacy of multisource 100 mcg levothyroxine sodium tablets (three sources, two brands, a total of five batches). Clinical efficacy and dissolution rate data varied among the tablet batches studied and indicated that brand/source interchangeability could not be claimed. The efficacy parameters showed good correlation with dissolution data generated under BP 2014, but not under USP 2014 dissolution test conditions. In the present study, we decided to expand the number of tablet batches studied in vitro to a total of 12, to report potency and content uniformity data missing in the clinical study, and to further examine the discrepancy in dissolution results based on the medium used. The wide range of batch age in the studied samples allowed investigating the effect of batch age on in-vitro tablet performance parameters. Generated potency values indicated the prevalence of super-potent tablet batches. The dissolution data reflected the effect of compendia monograph differences in dissolution medium. The results also indicated an inverse relationship between tablet potency and batch age and, between dissolution and batch age. The possible effect of potency results on the generated dissolution data was discussed. Statistical significance of correlations examined was assessed by linear and non-linear regression analysis. Statistical significance was evident for the relation between batch age and BP 2014 dissolution data, compared to USP 2014 dissolution results.

The study aimed to develop a patient-friendly acyclovir gel with improved efficacy in viral mouth infections, in response to patients' need for an intraoral acyclovir product. Acyclovir was loaded in lipid nanocapsules in gel form, and formulae were evaluated for oromucosal delivery. Lipid nanocapsules were prepared by the phase inversion method. Formulae were optimized to achieve maximum acyclovir entrapment and minimum acyclovir precipitation. Colloidal properties, and pharmaceutical performance indicators were assessed. Drug-loaded lipid nanocapsules were in the nanorange (39-120 nm), PdI (0.03-0.2), negative zeta potential, and entrapment efficiency (33-64%). Acyclovir (0.3% w/w) lipid nanocapsules gels were prepared using hydroxyethylcellulose (3% w/w). Resulting gel attributes were considered suitable. Lipid nanocapsules gels (0.3% w/w) showed enhanced Ex vivo acyclovir permeation across, and comparable retention in chicken pouch membrane compared to the 5% marketed cream despite lower drug content. The data provides basis for future exploration of lipid nanocapsules as carrier for transmucosal delivery of acyclovir; the enhanced acyclovir retention in chicken pouch membrane, compared to controls, suggests suitability of lipid nanocapsules for drug delivery to the viral lesion within the buccal membrane., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The present study investigates the effect of the preparation method (four methods) and formulation additives (propylene glycol (PG) and cholesterol (CH)) on the entrapment efficiency (EE) of pyridoxine hydrochloride (vitamin B6 (VB6)), representing hydrophilic water-soluble low permeable vitamins, in unilamellar liposomes. The main aim is to compare determined EE with predicted values generated using a web-published, computational model. Results showed that among the different preparation methods, modified film hydration showed significantly higher EE (p < 0.05). With regard to formulation additives, PG (5% w/v) produced smaller vesicles size with narrow size distribution. Agreement between determined and model-generated EE values was more evident in formulae with narrow size distribution (polydispersity index (PdI) below 0.23). Formulae containing PG showed slightly higher determined than predicted EE values indicating vitamin-phospholipid bilayer interaction. Meanwhile, agreement between determined and predicted EE was limited to VB6-to-phospholipid ratio below (1.2:2). The comparison provided further insight into the usefulness of the prediction model factors affecting agreement between determined and predicted EE data.

A clinical study was initiated in response to patients' complaints, supported by the treating physicians, of suspected differences in efficacy among multisource levothyroxine sodium tablets marketed in Egypt. The study design was a multiple dose (100μg levothyroxine sodium tablet once daily for 6 months) and involved 50 primary hypothyroidism female patients (5 equal groups). Tablets administered included five tablet batches (two brands, three origin locations) purchased from local pharmacies in Alexandria. Assessment parameters (measured on consecutive visits) included the thyroid stimulating hormone, total and free levothyroxine. Tablet dissolution rate was determined (BP/EP 2014 & USP 2014). In vitro vs in vivovs correlations were developed. Clinical and pharmaceutical data confirmed inter-brand and inter-source differences in efficacy. Correlations examined indicated potential usefulness of in vitro dissolution test in detecting poor performing levothyroxine sodium tablets during shelf life., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

This study aims at improving the buccal delivery of vitamin B6 (VB6) as a model highly water-soluble, low permeable vitamin. Two main strategies were combined; first VB6 was entrapped in liposomes, which were then formulated as mucoadhesive film. Both plain and VB6-loaded liposomes (LPs) containing Lipoid S100 and propylene glycol (∼ 200 nm) were then incorporated into mucoadhesive film composed of SCMC and HPMC. Results showed prolonged release of VB6 (72.65%, T50% diss 105 min) after 6h from LP-film compared to control film containing free VB6 (96.37%, T50% diss 30 min). Mucoadhesion was assessed both ex vivo on chicken pouch and in vivo in human. Mucoadhesive force of 0.2N and residence time of 4.4h were recorded. Ex vivo permeation of VB6, across chicken pouch mucosa indicated increased permeation from LP-systems compared to corresponding controls. Interestingly, incorporation of the vesicles in mucoadhesive film reduced the flux by 36.89% relative to LP-dispersion. Meanwhile, both films provided faster initial permeation than the liquid forms. Correlating the cumulative percent permeated ex vivo with the cumulative percent released in vitro indicated that LPs retarded VB6 release but improved permeation. These promising results represent a step forward in the field of buccal delivery of water-soluble vitamins., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Deformable liposomes and ethosomes were investigated as carriers for skin delivery of ketotifen (KT) in terms of vesicle size, entrapment efficiency, stability, in vitro permeation and skin deposition properties. Phosphatidylcholine (PC) from soybean lecithin was used in the preparation of all vesicles. Sodium cholate, sodium deoxycholate and Tween 80 were investigated as edge activators in preparation of KT deformable liposomes. KT ethosomes were prepared in two PC concentrations, 2% and 4.25% w/v, in 30% v/v ethanol. KT deformable liposomes showed improved entrapment efficiency over KT ethosomes. KT deformable liposomes with Tween 80 as an edge activator were more stable upon storage at 5 +/- 1 degree C than those prepared using sodium cholate or sodium deoxycholate and were more stable than KT ethosomes. In vitro permeation and skin deposition studies employed only deformable liposomes with Tween 80 as an edge activator and ethosomes with 4.25% w/v PC concentration. Both of them improved skin delivery of KT over controls and over traditional liposomes, with greater improvement of KT skin deposition than KT skin permeation, hence are more useful for dermal than for transdermal delivery of KT.

Formulation of local anesthetics in liposomal topical drug delivery system could provide a sustained and localized anesthesia. The aim of this study was to develop a liposomal dibucaine base (DB) local anesthetic delivery system. DB-loaded multilamellar vesicles (MLVs) were prepared through varying lipid composition, induced charge and pH of the hydration medium. Liposomes were characterized for morphology, size, entrapment efficiency (EE), in vitro drug release and stability including leakage stability. The percentage of drug entrapped in liposomes was found to be hydration medium pH dependent and charge dependent and more pronounced for negatively charged liposomes prepared using hydration medium of pH 9. In vitro release studies of liposomes have shown a sustained release of entrapped dibucaine compared to control solution. Results revealed that adjusting the various formulation variables of dibucaine base MLVs could yield stable and effective topical liposomal local anesthetic formulations.

Possible leakage of 5-fluorouracil from stable plurilamellar vesicles was monitored during storage of the liposomal concentrates, gels and lyophilized powders. Changes in release profile of dibucaine were taken as indicator of instability. Release profiles were obtained using the dialysis technique for a freshly prepared liposomal concentrate, gel or reconstituted lyophilized powder (zero time) and storage for one, two and four weeks in well closed tubes at 4 degrees C for the liposomal concentrate or gel and at 25 degrees C for liposomal lyophilized powder. Aiming at increasing stability of 5-fluorouracil liposomal dispersion, freshly prepared liposomal concentrates were directly incorporated in hydroxypropyl methylcellulose gel. Stability release profiles of liposomal gels and concentrates indicated a significant increase in stability of liposomal formulations. Also, lyophilization increases the shelf life of liposomes by preserving it in a dry form as a lyophilized cake to be reconstituted immediately prior to administration or direct incorporation into a final dosage form. Release and physico-chemical stability studies showed superior potentials of the lyophilized product after reconstitution in comparison to concentrate and gel forms. It could be concluded that lyophilization of liposomes loaded with a water-soluble drug such as 5-fluorouracil could significantly increase the stability of the liposomal vesicles and decrease leakage from it.

To explore the effect of dioctyl sodium sulfosuccinate on drug absorption in humans, the urinary excretion of a poorly absorbable drug, phenolsulfonphthalein, administered in solution with and without the surfactant was determined. Coadministration of a therapeutic dose of the surfactant with the drug solution resulted in a significant increase in the initial rate of absorption. A small increase in the extent of absorption was also observed. Pretreatment with the surfactant for 6 nights, followed by administration of the drug on the 7th day, did not significantly change the rate of extent of absorption. The surfactant is thought to have a direct effect on the GI membrane, resulting in a temporary change in its permeability. This effect appears to be reversible after a few hours.

Binding of prednisolone to rabbit tissue was determined experimentally and by computation to assess factors and proteins responsible for tissue distribution of this corticosteroid. Binding in tissue slices ranged from 36% in the lung to 83% in the liver. The results obtained were compared with steady-state tissue distribution data generated in vivo in the rabbit. Linear uptake with good agreement between the two sets of data was observed for the skeletal muscle and kidney, but not for the liver and lung. In vivo uptake of prednisolone in the liver is severely affected by metabolism and biliary excretion, while in vitro distribution into liver slices showed a pattern typical of saturation of a low-capacity site followed by linear nonspecific binding at higher concentrations. Specific saturable binding (K1 = 1.95 X 10(7) M-1) accounted for 74% of drug bound at a steroid concentration in the liver of 0.3 X 10(-6) M, but its contribution decreased to 5% at a concentration of 20 X 10(-6) M. Expected prednisolone binding in rabbit tissue was calculated based on various effective protein concentrations in tissues and binding parameters of prednisolone to rabbit plasma. The use of total Lowry protein concentrations markedly overestimates, while albumin (and transcortin) concentrations severely underestimate the tissue binding of prednisolone. The thiopental effective protein fraction best approximates the in vivo and tissue slice binding of prednisolone. Metabolism and saturable binding in liver complicate the otherwise relatively linear uptake of prednisolone into various tissues where macromolecules other than albumin dominate in tissue binding of the steroid.