Processes

Research

17 pages, 2175 KiB

Open AccessArticle

Method Development, Stability, and Pharmacokinetic Studies of Acyclovir-Loaded Topical Formulation in Spiked Rat Plasma

by Safar M. Alqahtani, Ali Altharawi, Mohammad A. Altamimi, Manal A. Alossaimi, Wael A. Mahdi, Mohhammad Ramzan and Afzal Hussain

Processes 2022, 10(10), 2079; https://doi.org/10.3390/pr10102079 - 14 Oct 2022

Cited by 7 | Viewed by 1618

Abstract

Acyclovir (ACV) is a synthetic acyclic nucleoside analogue active against herpes simplex virus type 1 and 2 (HSV-1 and HSV-2). The current research entails optimization, development, and validation of the sensitive, accurate, and precise high performance liquid chromatography-photo-diode array detector (HPLC-PDA) bioanalytical method [...] Read more.

Acyclovir (ACV) is a synthetic acyclic nucleoside analogue active against herpes simplex virus type 1 and 2 (HSV-1 and HSV-2). The current research entails optimization, development, and validation of the sensitive, accurate, and precise high performance liquid chromatography-photo-diode array detector (HPLC-PDA) bioanalytical method for quantification of ACV in rat plasma. The central composite design (CCD) of Design Expert (quality by design tool) was employed for identification of significant attributes (flow rate and concentration of buffer), which affected the performance of the developed method. The elution of ACV was achieved by separating the XBridge C₁₈ column and the mobile phase comprising of the potassium dihydrogen phosphate buffer (pH-6.8) and acetonitrile in a 90:10 v/v ratio pumped at a flow rate of 1.0 mL/ min. The method was validated as per International Council for Harmonization (ICH) guidelines in terms of selectivity, linearity, recovery, accuracy, and precision. The values of the lower limit of detection and the lower limit of quantification were found to be 30 and 100 ng/mL, respectively. Conclusively, the study showed superior performance with high robustness, sensitivity, and specificity of the developed bioanalytical method. The developed quantification method was applied for estimating pharmacokinetic (PK) parameters of ACV loaded vesicular systems (ethosomes, elastic liposomes, colloidal solution, and solution) transdermally applied to rat skin (using a previously published report). The method was successful in quantifying PK profiles for comparative assessment with a high robustness, re-validity, re-transferable, and simplicity approach. Full article

(This article belongs to the Special Issue Analysis, Determination and Pharmacokinetics of Active Substances in Drug Development)

► Show Figures

Figure 1

9 pages, 905 KiB

Open AccessArticle

Changes in High-Density Lipoprotein (HDL), Low-Density Lipoprotein (LDL) and Cholesterol Concentration in Heavy Cannabis Users: A Single-Centre Study in Cusco, Peru

by Sandro Cusihuaman, Jeel Moya-Salazar, Pedro Wong-Salgado, Marcia M. Moya-Salazar, Betsy Cañari, Karina Chicoma-Flores and Hans Contreras-Pulache

Processes 2022, 10(8), 1597; https://doi.org/10.3390/pr10081597 - 12 Aug 2022

Cited by 3 | Viewed by 6189

Abstract

Background: The effect of cannabis on cholesterol and lipid balance has been reported for decades. However, there are conflicting reports on the reduction of low-density lipoprotein (LDL-C) and total cholesterol. The purpose of this study was to determine the immediate changes of Cannabis [...] Read more.

Background: The effect of cannabis on cholesterol and lipid balance has been reported for decades. However, there are conflicting reports on the reduction of low-density lipoprotein (LDL-C) and total cholesterol. The purpose of this study was to determine the immediate changes of Cannabis spp. consumption by pyrolytic route in heavy users. Methods: A cross-sectional study on 20 Peruvian heavy cannabis users (mean age: 31 ± 9.5 years). The inclusion criteria were males with an average weight of 50–70 kg, normal BMI, and having used cannabis, without association with other drugs, for at least one year with a high frequency per week (use: 4–7 days/week). High-density lipoprotein (HDL-C), LDL-C, and total cholesterol were evaluated 30 and 120 min after the administration of Cannabis spp. (~0.2 g by inhalation). Results: Of the total 12 (60%), 10 (50%), and 11 (55%) had desirable total cholesterol, fairly good HDL-C (40–60 mg/dL) and fairly good LDL-C (100–129 mg/dL) values, respectively. The mean basal concentration of total cholesterol, HDL-cholesterol, and LDL-cholesterol was 193.37 ± 20.18 mg/dL, 60.05 ± 6.36 mg/dL, and 129.65 ± 14.50 mg/dL, respectively. HDL-cholesterol showed progressive increases in participants with desirable HDL-C > 60 mg/dL at 30 min (10 vs. 14 participants, p < 0.001) and at 120 min (10 vs. 16 participants, p < 0.001), while LDL-C peaked in participants with concentrations < 100 mg/dL at 30 min (desirable cholesterol: 0 vs. 2, p = 0.001). HDL-C concentration showed differences after cannabis consumption, showing increases at 30 (63.25 ± 7.68 mg/dL) and 120 min (69.15 ± 18.67 mg/dL) and total cholesterol concentration changed to 180.95 ± 19.3 mg/dL (95%CI 172.5 to 189.4) at 120 min (p = 0.007). Conclusions: HDL-C cholesterol increased 30 and 120 min after Cannabis spp. ingestion, while LDL-C and total cholesterol showed partial reductions in heavy-users from Cusco, Peru. Full article

(This article belongs to the Special Issue Analysis, Determination and Pharmacokinetics of Active Substances in Drug Development)

► Show Figures

Graphical abstract

15 pages, 7267 KiB

Open AccessArticle

3D-QSAR, ADME-Tox In Silico Prediction and Molecular Docking Studies for Modeling the Analgesic Activity against Neuropathic Pain of Novel NR2B-Selective NMDA Receptor Antagonists

by Mohamed El fadili, Mohammed Er-rajy, Hamada Imtara, Mohammed Kara, Sara Zarougui, Najla Altwaijry, Omkulthom Al kamaly, Aisha Al Sfouk and Menana Elhallaoui

Processes 2022, 10(8), 1462; https://doi.org/10.3390/pr10081462 - 26 Jul 2022

Cited by 23 | Viewed by 2369

Abstract

A new class of selective antagonists of the N-Methyl-D-Aspartate (NMDA) receptor subunit 2B have been developed using molecular modeling techniques. The three-dimensional quantitative structure–activity relationship (3D-QSAR) study, based on comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) [...] Read more.

A new class of selective antagonists of the N-Methyl-D-Aspartate (NMDA) receptor subunit 2B have been developed using molecular modeling techniques. The three-dimensional quantitative structure–activity relationship (3D-QSAR) study, based on comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) models, indicate that steric, electrostatic and hydrogen bond acceptor fields have a key function in the analgesic activity against neuropathic pain. The predictive accuracy of the developed CoMFA model (Q² = 0.540, R² = 0.980, R² pred = 0.613) and the best CoMSIA model (Q² = 0.665, R² = 0.916, R² pred = 0.701) has been successfully examined through external and internal validation. Based on ADMET in silico properties, L1, L2 and L3 ligands are non-toxic inhibitors of 1A2, 2C19 and 2C9 cytochromes, predicted to passively cross the blood–brain barrier (BBB) and have the highest probability to penetrate the central nervous system (CNS). Molecular docking results indicate that the active ligands (L1, L2 and L3) interact specifically with Phe176, Glu235, Glu236, Gln110, Asp136 and Glu178 amino acids of the transport protein encoded as 3QEL. Therefore, they could be used as analgesic drugs for the treatment of neuropathic pain. Full article

(This article belongs to the Special Issue Analysis, Determination and Pharmacokinetics of Active Substances in Drug Development)

► Show Figures

Figure 1

12 pages, 2808 KiB

Open AccessArticle

Acute Hepatic and Renal Toxicity Assessment of Euphorbia huanchahana (Klotzsch & Garcke) Boissier (Huachangana) in Holtzman Rats

by Graciela Villafuerte, Daniel Ñañez, Luis M. Félix, Marcia M. Moya-Salazar, Ernesto R. Torres-Véliz, Antonio G. Ramos, Hans Contreras-Pulache and Jeel Moya-Salazar

Processes 2022, 10(7), 1286; https://doi.org/10.3390/pr10071286 - 30 Jun 2022

Viewed by 1522

Abstract

Background: Euphorbia huachahana (Klotzch & Garcke) Boissier (Huachangana) (EhKGBh) has been used for over a century for medicinal purposes in the Peruvian population; however, its safety and possible toxic effects of use have not been reported. The purpose of this study was to [...] Read more.

Background: Euphorbia huachahana (Klotzch & Garcke) Boissier (Huachangana) (EhKGBh) has been used for over a century for medicinal purposes in the Peruvian population; however, its safety and possible toxic effects of use have not been reported. The purpose of this study was to determine the acute hepatic and renal toxicity of EhKGBh in Holtzman rats. Methods: Analytical and experimental study. The population consisted of 52 rats of both sexes weighing between 300 and 350 g divided into four groups: G1 and G2 EhKGBh groups (26 rats each) and two control groups (10 rats each). The experimental group was administered EhKGBh at a single dose of 2000 mg/kg P.O. to demonstrate toxicity during the 14-day follow-up. A daily assessment of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBIL), and conjugated bilirubin (CBIL) was performed. Results: Evaluation of the liver tissue showed mild changes in inflammation, predominantly vascular, with small clots. Kidney tissue did not show inflammatory or necrotic changes. However, we showed differences in the weight of the rats between both groups (p < 0.004) and significant increases in TBIL (0.98–1.07 mg/dL), CBIL (0.43–0.45 mg/dL), AST (126.4–141.8 U/L), and ALP (254–298 U/L) but not ALT (39.7–41.1 U/L) (p < 0.05). Conclusion: The single dose of EhKGBh extract at 2000 mg/kg has no toxicity, and there is no change in tissue toxicity during the 14-day follow-up. Full article

(This article belongs to the Special Issue Analysis, Determination and Pharmacokinetics of Active Substances in Drug Development)

► Show Figures

Figure 1

12 pages, 1528 KiB

Open AccessArticle

Parallel Reaction Monitoring Mode for Atenolol Quantification in Dried Plasma Spots by Liquid Chromatography Coupled with High-Resolution Mass Spectrometry

by Liliya V. Aksenova, Vladimir V. Koval and Alexander A. Chernonosov

Processes 2022, 10(7), 1240; https://doi.org/10.3390/pr10071240 - 22 Jun 2022

Cited by 1 | Viewed by 1576

Abstract

In this study, we reported a rapid, sensitive, robust, and validated method for atenolol quantification in dried plasma spots (DPS) by liquid chromatography with high-resolution mass spectrometry (LC-HRMS) using parallel reaction monitoring mode (PRM). Aliquots of 25 µL human plasma were placed onto [...] Read more.

In this study, we reported a rapid, sensitive, robust, and validated method for atenolol quantification in dried plasma spots (DPS) by liquid chromatography with high-resolution mass spectrometry (LC-HRMS) using parallel reaction monitoring mode (PRM). Aliquots of 25 µL human plasma were placed onto Whatman 903 Cards and air-dried. Disks (3.2 mm internal diameter) were punched, and a 100 µL working internal standard solution was added to each sample and then incubated on a shaker for 15 min at 40 °C, followed by rapid centrifugation (10,000× g, 10 s). The supernatant was transferred into 300 µL vials for subsequent LC–HRMS analysis. After chromatographic separation, atenolol and the internal standard were quantified in positive-ion parallel reaction monitoring mode by detection of all target product ions at 10 ppm tolerances. The total time of the analysis was 5 min. The calibration curve was linear in the range of 5–1000 ng/mL with interday and intraday precision levels and biases of <14.4%, and recovery was 62.9–81.0%. The atenolol in DPS was stable for ≥30 days at 25 and 4 °C. This fully validated method is selective and suitable for atenolol quantitation in DPS using LC–HRMS. Full article

(This article belongs to the Special Issue Analysis, Determination and Pharmacokinetics of Active Substances in Drug Development)

► Show Figures

Figure 1

12 pages, 1307 KiB

Open AccessArticle

Antibacterial and Antifungal Activity of Functionalized Cotton Fabric with Nanocomposite Based on Silver Nanoparticles and Carboxymethyl Chitosan

by Carlos Alberto Arenas-Chávez, Luciana Maria de Hollanda, Arturo A. Arce-Esquivel, Aldo Alvarez-Risco, Shyla Del-Aguila-Arcentales, Jaime A. Yáñez and Corina Vera-Gonzales

Processes 2022, 10(6), 1088; https://doi.org/10.3390/pr10061088 - 30 May 2022

Cited by 20 | Viewed by 3113

Abstract

Cotton is the most widely used natural fiber for textiles; however, the capacity of cotton fibers to absorb large amounts of moisture, retain oxygen, and have a high specific surface area makes them more prone to microbial contamination, becoming an appropriate medium for [...] Read more.

Cotton is the most widely used natural fiber for textiles; however, the capacity of cotton fibers to absorb large amounts of moisture, retain oxygen, and have a high specific surface area makes them more prone to microbial contamination, becoming an appropriate medium for the growth of bacteria and fungi. In recent years, the incorporation of silver nanoparticles in textile products has been widely used due to their broad-spectrum antibacterial activity and low toxicity towards mammalian cells. The aim of the current study is to continue the assessment of our developed nanocomposite and evaluate the antibacterial and antifungal activity of the nanocomposite based on silver nanoparticles and carboxymethyl chitosan (AgNPs-CMC) against Escherichia coli, Staphylococcus aureus, and Candida albicans, evaluated by the well diffusion method. The antibacterial activity against E. coli and S. aureus was also evaluated by the qualitative method of inhibition zone and the quantitative method of colony counting. Likewise, the antifungal activity of the functionalized fabric against Candida albicans and Aspergillus niger was determined by the inhibition zone method and the antifungal activity method GBT 24346-2009, respectively. The functionalized fabric showed 100% antibacterial activity against E. coli and S. aureus and good antifungal activity against C. albicans and A. niger. Our results indicate that the functionalized fabric could be used in garments for hospital use to reduce nosocomial infections. Full article

(This article belongs to the Special Issue Analysis, Determination and Pharmacokinetics of Active Substances in Drug Development)

► Show Figures

Figure 1

12 pages, 1537 KiB

Open AccessArticle

Preventive and Regenerative Effect of Glutamine and Probiotics on Gastric Mucosa in an Experimental Model of Alcohol-Induced Injury in Male Holtzman Rats

by Michelle Lozada-Urbano, Christian Pitot, Paulo Recoba-Obregón, Diego Paredes-Inofuente, Cristina Cáceres, Oriana Rivera-Lozada, Fiorella Inga-Berrospi and Cesar Bonilla-Asalde

Processes 2022, 10(3), 504; https://doi.org/10.3390/pr10030504 - 02 Mar 2022

Cited by 1 | Viewed by 8782

Abstract

Background: The purpose of this study was to measure the preventive and regenerative effect of glutamine and probiotics induced by alcohol injury in Holtzman rats. Methods: Analytical, experimental and prospective study. The population consisted of 56 male rats between 300 and 350 g, [...] Read more.

Background: The purpose of this study was to measure the preventive and regenerative effect of glutamine and probiotics induced by alcohol injury in Holtzman rats. Methods: Analytical, experimental and prospective study. The population consisted of 56 male rats between 300 and 350 g, distributed in three experimental phases: Pre-pilot phase PPP (6 rats), Pilot phase PP (10 rats), and Experimental phase EP (40 rats). In the pilot phase, 10 rats were subjected to damage with 8.5% ethanol, which was given intragastrically. The dosage was calculated for 10 rats in two groups: the first with 7.5 mL/kg in 5 rats and the second with 8.5 mL/kg in 5 rats. The experimental phase was performed in 40 rats divided into 6 groups, the negative control group (healthy), positive control group (injured), preventive experimental group (glutamine and glutamine with probiotic) and regenerative experimental group (glutamine and glutamine with probiotic). At the end of each phase, the rats were sacrificed with sodium pentobarbital (Halathal) and a portion of their stomachs was stored in formol. Results: The evaluation of stomach tissue samples (desquamation, erythema, hyperemia) showed that in the preventive phase, glutamine shows effectiveness in comparison to glutamine with probiotic. In the regenerative phase, glutamine and glutamine with probiotic did not show significant differences. Conclusions: Glutamine and probiotics can potentially serve as a therapy for the treatment for gastritis. Full article

(This article belongs to the Special Issue Analysis, Determination and Pharmacokinetics of Active Substances in Drug Development)

► Show Figures

Figure 1

12 pages, 1486 KiB

Open AccessArticle

Liquid Chromatography Tandem Mass Spectrometric Analytical Method for Study of Colchicine in Rats Given Low Doses

by Hamdah M. Al Nebaihi, Tyson S. Le, Neal M. Davies and Dion R. Brocks

Processes 2021, 9(11), 2007; https://doi.org/10.3390/pr9112007 - 10 Nov 2021

Cited by 4 | Viewed by 1882

Abstract

A selective and sensitive assay was developed for colchicine in rat specimens. Colchicine and its deuterated analog (as internal standard, IS) were extracted from rat specimens (minimal 0.1 mL plasma, whole blood, or urine) using liquid-liquid extraction with n-hexane:dichloromethane:isopropanol. The mobile phase (formic [...] Read more.

A selective and sensitive assay was developed for colchicine in rat specimens. Colchicine and its deuterated analog (as internal standard, IS) were extracted from rat specimens (minimal 0.1 mL plasma, whole blood, or urine) using liquid-liquid extraction with n-hexane:dichloromethane:isopropanol. The mobile phase (formic acid: ammonium acetate: methanol) was pumped with uniform flow through an octadecylsilane analytical column. Detection was carried out by electrospray positive ionization in the multiple-reaction monitoring mode. The assay (total run time <3 min) had excellent linearity over a wide (400–800-fold) concentration range. The mean absolute recovery was >96.8%. The intra- and inter-day coefficients of variation were ˂15%, with lower limits of quantitation of 0.5 ng/mL in 0.1 mL of rat plasma. The method also provided the same lower limits of quantitation in urine and whole blood with 0.1 mL volumes, and 0.1 ng/mL using 0.5 mL of rat plasma. The blood-to-plasma ratio was >1. Rats had measurable colchicine blood concentrations for at least 24 h after intravenous doses of 0.1 mg/kg. The method possessed suitable measures of sensitivity and selectivity for detecting colchicine in several specimen types in rats given low doses. Full article

(This article belongs to the Special Issue Analysis, Determination and Pharmacokinetics of Active Substances in Drug Development)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Analysis, Determination and Pharmacokinetics of Active Substances in Drug Development

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Published Papers (8 papers)

Research

Further Information

Guidelines

MDPI Initiatives

Follow MDPI