Pharmacological Evaluation Research Articles

Evaluation of Anti-depressant activity of Hibiscus rosa sinensis leaves in mice

Objective: The present is to evaluate antidepressant activity of ethanolic extract of Hibiscus rosa sinensis leaves using experimental animals. Method: The current study employed male Swiss albino mice weighing between 20 and 35 g and aged between 6 and 8 weeks. Hibiscus rosa sinensis extract were administered p.o to mice daily in two different doses (200 & 400 mg/kg/p.o) for 14 days regularly. After administration of the extract, the animal will be observed continuously for the first 2 hours and at 24 hrs to detect changes in behavioral responses and also for tremors, convulsion, salivation, diarrhea, lethargy, sleep, and coma and also will be monitored up to 14 days for the toxic symptoms and mortality. On 15th days, the animal subjected to Tail Suspension test (TST) and forced swim test (FST) and plasma corticosterone level. Result: The mice of Hibiscus rosa sinensis extract (200 & 400 mg/kg/p.o) treated group showed no significantly (p<0.05) difference in locomotors activity as compared to control group. Treatment with FXT (10 mg/kg p.o.)also showed no significant change as compared to control group. The above observation suggests that Hibiscus rosa sinensis leaves has antidepressant activity. Conclusion: The Ethanolic extract of Hibiscus rosa sinensis 400 mg/kg showed the most remarkable activity. This plant can be further subjected to isolation of the therapeutic Antidepressant compound and carry out further pharmacological evaluation. Keywords: Depression, herbal medications. Hibiscus rosa sinensis, antidepressant plants

Synthesis, Characterisation, Computational ADME studies, Pharmacological screening and In-vitro Hydrolysis studies of potential novel mutual prodrugs of N-(2,3-xylyl anthranillic acid)

In the present work we report Synthesis, Computational ADME study, Pharmacological evaluation and In-vitro hydrolysis study of new mutual prodrugs of N-(2,3-xylyl anthranillic acid) prepared with and without spacer using Dicyclohexylcarbodiimide (DCC) as coupling agent. The structures of mutual prodrugs formed were confirmed by advanced spectroscopic techniques. The title compounds were tested for analgesic activity by Eddy’s hot plate and tail-flick method; for anti-inflammatory activity by carrageenan induced rat paw edema method and for ulcerogenicity and acute oral toxicity. Title compounds exhibited promising analgesic and anti-inflammatory activity. The compounds were found to be devoid of ulcerogenicity at the test dose level and presented significant values of the ADME properties studied, obeying Lipinski Rule of five violations, good oral absorption and lipophilicity. Hydrolysis studies revealed that the compounds were sufficiently stable at pH 1.2, indicating that no appreciable hydrolysis to the free acids might occur in the stomach. The amount of free drug released on hydrolysis in 80% human plasma (pH 7.4) was greater than that released in aqueous buffers, suggesting that the rate of hydrolysis of compounds in 80% human plasma was markedly accelerated compared with that in aqueous buffers.

Synthesis and Pharmacological Evaluation of 3-alkyl/aryl–2- methylquinazolin-4-one Derivatives

Quinazolin-4-ones with 2, 3-disubstitution is reported to possess significant analgesic, anti-inflammatory and anticonvulsant activities. We have developed an efficient method for the synthesis of 3-substituted-2-methylquinazolin-4-one by the condensation reaction of Anthranilic acid, acetic anhydride with various amines. The synthesized compounds were evaluated for anxiolytic activity by Elevated plus Maze Test and Light and Dark Test. It is observed that the aliphatic and aromatic substitution at 3-position of 2-methylquinazolin-4-one gives potent anxiolytic activity. In particular, ENA showed highest anxiolytic activity in Elevated plus Maze Test and EMQ and AMQ showed highest anxiolytic activity in Light and dark test model

Phytochemical characterization and evaluation of anti-amnesic activity of two source plants of Shankhapushpi

BackgroundShankhapushpi is an important Ayurvedic drug used for treating various disease conditions of nervous system. Convolvulus prostratus Forssk. is the genuine source plant for Shankhapushpi as per Ayurvedic Pharmacopoeia of India; however Clitorea ternatea L. is widely used as Shankhapushpi in southern part of India. In this study, comparative phytochemical and pharmacological evaluation has been done in two plants such as Convolvulus prostratus and Clitorea ternatea used as Shankhapushpi. MethodsPhytochemical comparison was done by High Performance Thin Layer Chromatography (HPTLC) and High Performance Liquid Chromatography (HPLC). Detailed metabolite profiling was performed using Q-TOF-LC/MS-MS analysis. Antiamnesic activity of selected plants has been evaluated against scopolamine induced amnesia model in Wistar rats. ResultsPhytochemical studies showed that only a few chemical constituents are common for both species. Most of the phytochemicals are different for selected species. LC/MS analysis showed presence of genipin and 7-hydroxyflavone in both species. Pharmacological study showed that both plants possess antiamnesic activity against Scopolamine induced memory loss; However C. ternatea possesses significant antiamnesic activity than that of C. prostratus. ConclusionThe study provided valuable information about the selected species in terms of its phytochemical composition and pharmacological properties. The study also provided a scientific support for using both species as Shankhapushpi.

Recent Advances in Pyrazole-based Protein Kinase Inhibitors as Emerging Therapeutic Targets.

Pyrazole-scaffold protein kinase inhibitors (PKIs) have emerged as promising therapeutic agents for the treatment of various diseases, such as cancer, inflammatory disorders, and neurological diseases. This review article provides an overview of the pharmacological properties of pyrazole-scaffold PKIs, including their mechanism of action, selectivity, potency, and toxicity. The article also summarizes the recent developments in the design and synthesis of pyrazole-scaffold PKIs, highlighting the structural features and modifications that contribute to their pharmacological activity. In addition, the article discusses the preclinical and clinical studies of pyrazole-scaffold PKIs, including their efficacy, safety, and pharmacokinetic properties. A comprehensive search has been conducted on several online patent databases, including the United States Patent and Trademark Office (USPTO), the European Patent Office (EPO), and the World Intellectual Property Organization (WIPO). The search was conducted using pyrazole as the keyword. The search was limited to patents filed between 2015 and 2022. Patents were included if they involved articles in the fields of protein kinase inhibitors, and included literature on some pyrazoles and their pharmacological activities. Data were extracted from each included patent on the following variables: patent title, patent number, inventors, assignee, filing date, publication date, patent type, and field of invention. Data were extracted from each patent using a standardized form to ensure consistency and accuracy. The design and pharmacological evaluation of organic compounds containing pyrazole structure as biologically active substances have been done, and the key structures from the pharmacological data obtained as protein kinase inhibitors have been addressed in detail. The review concludes with a discussion on the current challenges and future directions for the development of pyrazole-scaffold PKIs as therapeutic agents. Overall, this review article provides a comprehensive summary of the pharmacological properties of pyrazole-scaffold PKIs, which will be of interest to researchers and clinicians in the field of drug discovery and development.

Colistin-niclosamide effervescent dry suspension combats colistin-resistant Salmonella in vitro and in vivo

The increasing incidence of bacterial infections caused by multidrug-resistant (MDR) Gram-negative bacteria has deepened the need for new effective treatments. It has been reported that niclosamide (NIC) can restore the sensitivity of Gram-negative bacteria to colistin (COL). However, NIC is practically insoluble in water and sparingly soluble in organic solvents, leading to limited therapeutic applications. This study aims to prepare a COL-NIC effervescent dry suspension (CNEDS) and evaluate its antibacterial effect against COL-resistant Salmonella both in vitro and in broiler chickens. With the sedimentation volume ratio as an index, suitable suspending agent, wetting agent, filler and effervescent agent were screened through a single-factor method. The preparation conditions were optimized using the Box-Behnken response surface method to obtain the formulation for CNEDS. The quality evaluation results showed that the successfully prepared CNEDS had a sedimentation volume ratio of 0.99, a drying weight loss of 1.3%, and a re-dispersion capability of 1-2 times, all of which met pharmacopoeial requirements. In terms of pharmacological evaluation, we first demonstrated that CNEDS substantially restored COL sensitivity against COL-resistant bacteria. Subsequently, time-killing analysis, scanning electron microscopy (SEM) and live/dead assays confirmed the antibacterial activity of CNEDS against COL-resistant bacteria. Finally, a Salmonella infection model in broiler chickens was established to further assess the therapeutic effect of CNEDS in vivo. CNEDS improved the survival rate of broiler chickens, reduced the bacterial burden on organs. These findings suggest that CNEDS effectively overcome COL resistance, indicating its potential for the treatment of COL-resistant bacterial infections in broiler chickens.

Characterization of novel nitazene recreational drugs: Insights into their risk potential from in vitro µ-opioid receptor assays and in vivo behavioral studies in mice

2-Benzylbenzimidazole derivatives or ‘nitazenes’ are increasingly present on the recreational drug market. Here, we report the synthesis and pharmacological characterization of 15 structurally diverse nitazenes that might be predicted to emerge or grow in popularity. This work expands the existing knowledge about 2-benzylbenzimidazole structure-activity relationships (SARs), while also helping stakeholders (e.g., forensic toxicologists, clinicians, policymakers) in their risk assessment and preparedness for the potential next generation of nitazenes. In vitro µ-opioid receptor (MOR) affinity was determined via competition radioligand (3[H]DAMGO) binding assays in rat brain tissue. MOR activation (potency and efficacy) was studied by means of a cell-based β-arrestin 2 recruitment assay. For seven nitazenes, including etonitazene, opioid-like pharmacodynamic effects (antinociception, locomotor activity, body temperature changes) were evaluated after subcutaneous administration in male C57BL/6J mice. The results showed that all nitazenes bound to MOR with nanomolar affinities, and the functional potency of several of them was comparable to or exceeded that of fentanyl. In vivo, dose-dependent effects were observed for antinociception, locomotor activity, and body temperature changes in mice. SAR insights included the high opioid-like activity of methionitazene, iso-butonitazene, sec-butonitazene, and the etonitazene analogues 1-ethyl-pyrrolidinylmethyl N-desalkyl etonitazene and ethylene etonitazene. The most potent analogue of the panel across all functional assays was α’-methyl etonitazene. Taken together, through critical pharmacological evaluation, this work provides a framework for strengthened preparedness and risk assessments of current and future nitazenes that have the potential to cause harm to users.

Pharmacological evaluation of rice varieties, Hassawi and Njavara

Hasswai and Njavara are two notable international and Indian red rice cultivars that provide a variety of nutrients and phytochemicals. An effort was made to investigate the pharmacological properties of these rice types. In conclusion, both types of rice exhibit lipid peroxidation, acetylcholinesterase, thrombolytic, anti-arthritic, antioxidant, and anti-inflammatory properties. Methanol extracts showed increased acetylcholinesterase, thrombolytic, and antioxidant activity in the current investigation. On the other hand, aqueous extracts have stronger anti-inflammatory, anti-arthritic, lipid peroxidation, protease inhibition, and amylose inhibitory properties. Of these two varieties, Hasawi showed good activities concerning amylose inhibition, thrombolytic activity, antioxidant activity, and anti-inflammatory and lipid peroxidation. However good protease inhibition and acetylcholinesterase activities were noted in Njavara than in Hasawi. This points to a specific phytochemical composition that these two rice varieties contain. More detailed investigations are warranted to score the exact phytochemical basis for the observed activities.

Exploring the therapeutic potential of Coffea arabica: pharmacological evaluation of extracts, fractions, and isolated compounds to treat diabetes and to treat diabetes-associated hepatic dysfunction and dyslipidemia in rats

Coffea arabica is one of the most widely consumed beverages, used to combat fatigue, improve concentration, enhance alertness and to treat headaches and migraines. It also has antioxidant properties. Cohort studies suggest a reduced risk of type 2 diabetes among coffee drinkers, prompting investigations into compounds other than caffeine. This study investigated the impact of C. arabica on diabetes, specifically its efficacy in alleviating diabetes-induced hepatic dysfunction and dyslipidemia. Initial assessments involved the extraction of coffee, followed by fractionation and isolation of a compound that was subjected to rigorous pharmacological evaluation to determine their potential therapeutic effects. Preliminary findings suggest promising therapeutic effects of coffee in managing diabetes. The study sheds light on the potential of C. arabica for ameliorating diabetes-associated dyslipidemia and hepatic dysfunction. Overall, the therapeutic potential of coffee for treating diabetes and associated complications, emphasising the need for further exploration and clinical translation of these findings.

Efficacy and in vitro pharmacological assessment of novel N-hydroxypyridinediones as hepatitis B virus ribonuclease H inhibitors.

We previously reported N-hydroxypyridinedione (HPD) compounds with mid-nanomolar efficacy and selectivity indexes around 300 against hepatitis B virus (HBV) replication. However, they lack pharmacological evaluation. Here, we report in vitro anti-HBV efficacy, cytotoxicity, and pharmacological characterization of 29 novel HPDs within seven subgroups. The best two compounds had EC50s of 61 and 190 nM and selectivity indexes of 526 and 1,071. Compounds with one halogen on the major R group were most effective and compounds with large ether R groups were most cytotoxic. Compounds were not cytotoxic in primary human hepatocytes. All compounds were freely soluble in pHs reflecting plasma (7.4) and the gastrointestinal tract (5 and 6.5). Almost all highly soluble compounds were passively permeable at pH 5.0 and 7.4. Only 2 of 11 compounds tested were likely to be effluxed by p-glycoprotein. The most potent HPDs inhibited HBV replication over human ribonuclease H1 activity by 10-fold. Four of 19 compounds inhibited CYP2D6 >50%, but their CYP2D6 IC50s were >8× higher than their anti-HBV EC50. No compound substantially inhibited CYP3A4. Thirteen of 15 compounds had human microsomal half-lives >30 min with medium to low rates of intrinsic clearance. Eleven of 12 compounds bound plasma proteins by ≥80%; however, effects against HBV replication for only one would likely be physiologically relevant. These results identify two lead candidate HPDs with pharmacological characteristics resembling commercially available drugs that are suitable for in vivo pharmacological and efficacy studies.

Pharmacological Evaluation of Bakuchiol From Psoralea corylifolia L. as Potent Antimicrobial Agent Against Staphylococcus aureus.

The surge in multidrug resistance in Staphylococcus aureus is the pressing need to identify novel alternatives to combat antimicrobial resistance effectively. Bakuchiol is a bioactive prenylated phenolic meroterpene largely abundant in the seeds of Psoralea corylifolia. In this study, we present the biological assessment of bakuchiol derived from P. corylifolia as an antimicrobial agent. S. aureus, a significant opportunistic pathogen, attracts global concern for its biofilm formation and resilience against numerous antibiotics, escaping antibiotic pressure. The primary screening of bakuchiol as an antimicrobial agent against S. aureus delineated its potential as a strong bactericidal agent with a minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of 2 and 8µg/mL, respectively. Importantly, bakuchiol also exhibited low toxicity against HepG2 cells, showing a favorable selectivity index (SI) of 14.4. Furthermore, bakuchiol demonstrated comparable activity (MIC=2µg/mL) against a laboratory-generated ciprofloxacin-resistant mutant of S. aureus. Bakuchiol could significantly inhibit the biofilm formation of S. aureus in a dose-dependent manner with minimum biofilm inhibitory concentration (MBIC)50 of 0.956µg/mL. Bakuchiol effectively inhibited DNA gyrase supercoiling activity at a concentration eight times the MIC, establishing DNA gyrase inhibition as the mechanism of action for bakuchiol. Our findings suggest bakuchiol as a potential therapeutic agent for S. aureus-mediated nosocomial infections.

Comparative Metabolomic Analysis and Antinociceptive Effect of Methanolic Extracts from Salvia cinnabarina, Salvia lavanduloides and Salvia longispicata.

Mexico is considered one of the countries with the greatest diversity of the Salvia genus. A significant percentage of its species are known for their use in traditional medicine, highlighting their use as an analgesic. The objective of this work was to determine the chemical composition of the methanolic extracts of S. cinnabarina, S. lavanduloides and S. longispicata through untargeted metabolomics, as well as the in vivo evaluation of the antinociceptive effect and acute oral toxicity. The chemical profiling was performed using ultra-high performance liquid chromatography coupled with a high-resolution mass spectrometry (UPLC-ESI+/--MS-QTOF) system and tentative identifications were performed using a compendium of information on compounds previously isolated from Mexican species of the genus. Pharmacological evaluation was carried out using the formalin test and OECD guidelines. The analysis of the spectrometric features of the mass/charge ratios of the three salvias shows that a low percentage of similarity is shared between them. Likewise, the putative identification allowed the annotation of 46 compounds, mainly of diterpene and phenolic nature, with only four compounds shared between the three species. Additionally, the extracts of the three salvias produced a significant antinociceptive effect at a dose of 300 mg/kg administered orally and did not present an acute oral toxicity effect at the maximum dose tested, indicating a parameter of LD50 > 2000 mg/kg. The exploration of the chemical profile of the three salvias by untargeted metabolomics shows that, despite being species with antinociceptive potential, they have different chemical profiles and therefore different active metabolites.

Pharmacological Evaluation of the Traditional Brazilian Medicinal Plant Monteverdia ilicifolia in Gastroesophageal Reflux Disease: Preliminary Results of a Randomized Double-Blind Controlled Clinical Trial.

The present work aimed to compare the effects of the standardized dry extract from the leaves of Monteverdia ilicifolia, popularly known as "espinheira-santa", with omeprazole in the management of dyspepsia related to gastroesophageal reflux disease (GERD). A double-blind, randomized, non-inferiority and double-dummy clinical trial was conducted. In total, 86 patients with GERD symptoms were randomized into three groups: Omeprazol (20 mg), M. ilicifolia (400 mg), or M. ilicifolia (860 mg). Capsules were provided by SUSTENTEC®, Pato Bragato, Brazil. It was requested that the participants take three capsules before breakfast and dinner for 4 weeks. Clinical outcomes were obtained at the beginning and end of the study, with GERD symptoms (QS-GERD), the impact of heartburn symptoms on quality of life (HBQOL), and medical records. Overall, 75.6% of the participants showed adherence without any differences among the experimental groups. All groups had significant reductions in both QS-GERD and HBQOL scores. Omeprazole and 400 and 860 mg of M. ilicifolia decreased the QS-GERD total scores at the endpoint compared to the baseline (Chi-square = 129.808; p < 0.0001), as well as individual item scores, such as heartburn intensity (Chi-square = 93.568, p < 0.0001) and heartburn after meals (Chi-square = 126.426, p < 0.0001). There were no differences among the experimental groups after the intervention. Our results suggest that capsules with a standardized dry extract from the leaves of M. ilicifolia at a dosage of 400 or 860 mg are non-inferior to omeprazole, a proton pump inhibitor.

Cancer Cells Show Higher Sensitivity to Melatonin-Tamoxifen Drug Conjugates than to Combination of Melatonin and Tamoxifen.

Drug conjugates of tamoxifen and melatonin linked through the amide side chain of melatonin (4a,4b) were reported as promising agents for future treatment of breast cancer, possibly reversing the adverse effects of tamoxifen. Here, we report the synthesis and pharmacological evaluation of a novel series of anticancer drug conjugates linking melatonin with tamoxifen through polymethylene spacers through the ether oxygen of melatonin (16a-c, 19a-c, 21) and compare them to the previously reported amide-linked analogues 4a and 4b. All hybrid ligands are antagonists of estrogen receptor alpha and agonists of the melatonin MT1 receptor with variable potencies. Several drug conjugates including the (CH2)4-linked analogues 4a and 16a and the (CH2)6-linked compound 16c showed higher potency to inhibit cell viability than the combination of melatonin and tamoxifen on at least one cancer cell line including MCF-7, MDA-MB-231, and HT-1080.

Phenotypic characterization of periwinkle (Catharanthus roseus L. G. Don.) for the selection of promising materials for breeding programs

Catharanthus roseus germplasm in India is predominantly inbred, implying the importance of accessing and detecting morphological variability in order to find acceptable genotypes with desired characteristics for novel variety generation and pharmacological evaluation. Seventeen morphological features were used to characterise the 25 C. roseus accessions. The current study found significant variance in qualitative and quantitative morphological features, despite 14 variables showing significant dissimilarity among accessions. The majority of the target features differed significantly (p < 0.05) between the analysed accessions. The PCA grouping pattern revealed the characteristics as the five main components, which could explain the total 74.06% variation. The dendrogram created from the recorded attributes revealed three distinct clusters as well as significant variability across the accessions investigated. The best-performing accession among twenty-five accessions collected with respect to morphology was Cr00PFRE and Cr00LPFLPE, which had maximum leaf size and plant height, respectively. The findings of this work show that the accessions analysed can be considered a representative gene pool of C. roseus.

Synthesis and pharmacological activity evaluation of 2-(2-Phenylethyl)chromone analogues: The principal components in agarwood

2-(2-Phenylethyl)chromones (PECs), the pivotal constituents responsible for the distinctive aroma and pharmacological potential of agarwood, are primarily obtained through extraction from natural materials. The restricted availability of agarwood has, however, hindered a comprehensive and systematic evaluation of their biological properties. In this study, we have chemically synthesized a total of 38 PEC derivatives, including 23 new compounds that had not been previously isolated from agarwood. These compounds were then evaluated for their inhibitory effects on nitric oxide release, neutrophil superoxide production, as well as their activities against tyrosinase, acetylcholinesterase, and α-glucosidase. The preliminary screening resulted in the identification of promising leads with potential therapeutic activities, and the structure-activity relationship of the synthesized PECs have also been briefly discussed. The results provide a foundation for the synthesis and pharmacological exploration of PECs, which sheds light on the pharmacological potential of agarwood's secondary metabolites.

Pharmacological Evaluation of Anti-Inflammatory and Antioxidant Potential of Cuscuta Reflexa Methanol Extract: Role in Inhibition of Cyclooxygenase and Lipooxygenase

In this study, the antioxidant and anti-inflammatory properties of the methanol extract of Cuscuta reflexa (CRWP-M) were evaluated. The plant material was collected from Dehradun and processed to obtain the extract, which was tested for its total phenolic content, reducing power, and scavenging activities against DPPH and superoxide radicals. The extract's inhibition of cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and 5-lipoxygenase (LOX) enzymes was also assessed. Results showed that the extract contained 0.132 mg/mL of gallic acid equivalents of phenolic compounds. In the reducing power assay, the extract demonstrated lower activity compared to Quercetin and Vitamin C across all concentrations. For DPPH radical scavenging, the extract was more effective than BHT at low concentrations but less effective at higher concentrations. The extract exhibited a dose-dependent inhibition of COX-1, COX-2, and LOX, with the most significant effect on LOX (IC50 of 106.49 μg/mL). In superoxide radical scavenging, Vitamin C consistently outperformed the extract at all tested concentrations. These findings suggest that while CRWP-M has notable antioxidant and anti-inflammatory properties, its efficacy varies across different assays and is generally lower than that of standard antioxidants like Quercetin and Vitamin C.

3D bioprinted in vitro epilepsy models for pharmacological evaluation in temporal lobe epilepsy

This study introduces a novelin vitromodel for intractable temporal lobe epilepsy (TLE) utilizing 3D bioprinting technology, aiming to replicate the complex neurobiological characteristics of TLE more accurately. Primary neural cell constructs were fabricated and subjected to epileptiform-inducing conditions, fostering synaptic proliferation and neuronal loss. Systematically electrophysiological and immunofluorescent analyses indicated that significant synaptic connectivity and sustained epileptiform activities within the constructs akin to those observed in human epilepsy models. Notably, the model responded to treatments with phenytoin and tetrodotoxin, illustrating its potential utility in drug response kinetics studies. Furthermore, we performed drug permeability simulations using COMSOL Multiphysics to analyze the diffusion characteristics of these drugs within the constructs. These results confirm that our 3D bioprinted neural model provides a physiologically relevant and ethically sustainable platform, which is beneficial for studying TLE mechanisms and developing therapeutic strategies with high accuracy and clinical relevance.

Bioengineering the Human Intestinal Mucosa and the Importance of Stromal Support for Pharmacological Evaluation In Vitro.

Drug discovery is associated with high levels of compound elimination in all stages of development. The current practices for the pharmacokinetic testing of intestinal absorption combine Transwell® inserts with the Caco-2 cell line and are associated with a wide range of limitations. The improvement of pharmacokinetic research relies on the development of more advanced in vitro intestinal constructs that better represent human native tissue and its response to drugs, providing greater predictive accuracy. Here, we present a humanized, bioengineered intestinal construct that recapitulates aspects of intestinal microanatomy. We present improved histotypic characteristics reminiscent of the human intestine, such as a reduction in transepithelial electrical resistance (TEER) and the formation of a robust basement membrane, which are contributed to in-part by a strong stromal foundation. We explore the link between stromal-epithelial crosstalk, paracrine communication, and the role of the keratinocyte growth factor (KGF) as a soluble mediator, underpinning the tissue-specific role of fibroblast subpopulations. Permeability studies adapted to a 96-well format allow for high throughput screening and demonstrate the role of the stromal compartment and tissue architecture on permeability and functionality, which is thought to be one of many factors responsible for unexpected drug outcomes using current approaches for pharmacokinetic testing.

Pharmacologic evaluation of delayed long-acting cabotegravir administration among cisgender women in HPTN 084.

This study is registered with ClinicalTrials.gov as NCT03164564.