Vol 30, No 32 (2024)

Immunology, Inflammation & Allergy

A Quest for Potential Role of Vitamin D in Type II Diabetes Mellitus Induced Diabetic Kidney Disease

Obaid A., Farrash W., Mujalli A., Singh S.

Abstract

:Diabetes mellitus is a metabolic disorder characterized by high blood sugar levels. In recent years, T2DM has become a worldwide health issue due to an increase in incidence and prevalence. Diabetic kidney disease (DKD) is one of the devastating consequences of diabetes, especially owing to T2DM and the key clinical manifestation of DKD is weakened renal function and progressive proteinuria. DKD affects approximately 1/3rd of patients with diabetes mellitus, and T2DM is the predominant cause of end-stage kidney disease (ESKD). Several lines of studies have observed the association between vitamin D deficiency and the progression and etiology of type II diabetes mellitus. Emerging experimental evidence has shown that T2DM is associated with various kinds of kidney diseases. Recent evidence has also shown that an alteration in VDR (vitamin D receptor) signaling in podocytes leads to DKD. The present review aims to examine vitamin D metabolism and its correlation with T2DM. Furthermore, we discuss the potential role of vitamin D and VDR in diabetic kidney disease.

Current Pharmaceutical Design. 2024;30(32):2505-2512
pages 2505-2512 views

Scope and Application of Hot Melt Extrusion in the Development of Controlled and Sustained Release Drug Delivery Systems

Joshi P., Rao G., Chatterjee B.

Abstract

Controlled-release drug delivery systems (CRDDS) are more beneficial than conventional immediate release (IRDDS) for reduced intake, prolonged duration of action, lesser adverse effects, higher bioavailability, etc. The preparation of CRDDS is more complex than IRDDS. The hot melt extrusion (HME) technique is used for developing amorphous solid dispersion of poorly water soluble drugs to improve their dissolution rate and oral bioavailability. HME can be employed to develop CRDDS. Sustained release delivery systems (SRDDS), usually given orally, can also be developed using HME. This technique has the advantages of using no organic solvent, converting crystalline drugs to amorphous, improving bioavailability, etc. However, the heat sensitivity of drugs, miscibility between drug-polymer, and the availability of a few polymers are some of the challenges HME faces in developing CRDDS and SRDDS. The selection of a suitable polymer and the optimization of the process with the help of the QbD principle are two important aspects of the successful application of HME. In this review, strategies to prepare SRDDS and CRDDS using HME are discussed with its applications in research.
Current Pharmaceutical Design. 2024;30(32):2513-2523
pages 2513-2523 views

Key Challenges, Influencing Factors, and Future Perspectives of Nanosuspensions in Enhancing Brain Drug Delivery

Wang W., Yang C., Xue L., Wang Y.

Abstract

Many brain diseases pose serious challenges to human life. Alzheimer's Disease (AD) and Parkinson's Disease (PD) are common neurodegenerative diseases that seriously threaten human health. Glioma is a common malignant tumor. However, drugs cannot cross physiological and pathological barriers and most therapeutic drugs cannot enter the brain because of the presence of the Blood-brain Barrier (BBB) and Bloodbrain Tumor Barrier (BBTB). How to enable drugs to penetrate the BBB to enter the brain, reduce systemic toxicity, and penetrate BBTB to exert therapeutic effects has become a challenge. Nanosuspension can successfully formulate drugs that are difficult to dissolve in water and oil by using surfactants as stabilizers, which is suitable for the brain target delivery of class II and IV drugs in the Biopharmaceutical Classification System (BCS). In nanosuspension drug delivery systems, the physical properties of nanostructures have a great impact on the accumulation of drugs at the target site, such as the brain. Optimizing the physical parameters of the nanosuspension can improve the efficiency of brain drug delivery and disease treatment. Therefore, the key challenges, influencing factors, and future perspectives of nanosuspension in enhancing brain drug delivery are summarized and reviewed here. This article aims to provide a better understanding of nanosuspension formulation technology used for brain delivery and strategies used to overcome various physiological barriers.
Current Pharmaceutical Design. 2024;30(32):2524-2537
pages 2524-2537 views

Maximizing Treatment Options for IBD through Drug Repurposing

Barjasteh A., Al-Asady A., Latifi H., Al Okla S., Al-Nazwani N., Avan A., Khazaei M., Ryzhikov M., Nadi-Yazdi H., Hassanian S.

Abstract

Chronic inflammation characterizes Inflammatory Bowel Disease (IBD), encompassing Crohn's Disease (CD) and Ulcerative Colitis (UC). Despite modest activity of disease in most UC patients, exacerbations occur, especially in those with severe symptoms, necessitating interventions, like colectomy. Current treatments for IBD, predominantly small molecule therapies, impose significant economic burdens. Drug repurposing offers a cost-effective alternative, leveraging existing drugs for novel therapeutic applications. This approach capitalizes on shared molecular pathways across diseases, accelerating therapeutic discovery while minimizing costs and risks. This article provides an overview of IBD and explores drug repurposing as a promising avenue for more effective and affordable treatments. Through computational and animal studies, potential drug candidates are categorized, offering insights into IBD pathogenesis and treatment strategies.
Current Pharmaceutical Design. 2024;30(32):2538-2549
pages 2538-2549 views

New Insights in Psoriasis Management using Herbal Drug Nanocarriers

Salgaonkar S., Purewal J., Doshi G., Fernandes T., Gharat S., Sawarkar S.

Abstract

Psoriasis (Pso) is an autoimmune inflammatory skin disease characterized by red plaques covered in silver scales. The existing treatments provide limited benefits and are associated with certain drawbacks which limit their use. Thus, there is a need to explore more options that are highly target-specific and associated with minimal side effects. Researchers have thoroughly investigated the use of herbal drugs for their therapeutic potential. Preclinical studies demonstrate that phytochemicals such as curcumin, psoralen, and dithranol have antipsoriatic effects. These phytoconstituents inhibit the signalling pathways, such as the interleukin (IL) 23/Th17 axis and IL-36 inflammatory loop involved in the pathogenesis of Pso. These phytoconstituents down-regulate the pro-inflammatory cytokines like IL-17 and tumor necrosis factor (TNF)-α. However, their application in clinical settings is limited due to poor bioavailability and access to target sites. Combining phytoconstituents with modern delivery platforms like nanocarriers can address these shortcomings and improve therapeutic efficacy. This review explores the potential of herbal remedies as a substitute for conventional therapies, emphasizing the clinical trials conducted with these herbal medicines. The paper is supported by the discussion on nanocarriers like liposomes, niosomes, emulsomes, ethosomes, nanostructured lipid carriers, nanoemulsions, and dendrimers that are used to deliver herbal medicines.
Current Pharmaceutical Design. 2024;30(32):2550-2561
pages 2550-2561 views

Role of Natural Products against the Spread of SARS-CoV-2 by Inhibition of ACE-2 Receptor: A Review

Sharma K., Devi S., Kumar D., Ali Z., Fatma N., Misra R., Kumar G.

Abstract

A unique extreme acute breathing syndrome emerged in China and spread rapidly globally due to a newly diagnosed human coronavirus and declared a pandemic. COVID-19 was formally named by WHO, and the Global Committee on Taxonomy referred to it as extreme Acute respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Currently there is no efficient method to control the extent of SARS-CoV-2 other than social distancing and hygiene activities. This study aims to present a simple medicinal strategy for combating fatal viral diseases like COVID-19 with minimum effort and intervention. Different Ayurveda medicines (Curcuma longa, green tea, and Piper nigrum) inhibit virus entrance and pathogen transmission while also enhancing immunity. Piperine (1-piperoylpiperidine), as well as curcumin, combine to create an intermolecular complex (π- π) that improves curcumin bioavailability by inhibiting glucuronidation of curcumin in the liver. The receptor- binding domains of the S-protein and also the angiotensin-converting enzyme 2 receptor of the recipient organism are directly occupied by curcumin and catechin, respectively, thereby preventing viruses from entering the cell. As a result, the infection will be tolerated by the animal host.
Current Pharmaceutical Design. 2024;30(32):2562-2573
pages 2562-2573 views

A Rapid, Sensitive, and High-throughput Method for the Simultaneous Determination of Antihypertensive Drug Combinations in Dog Plasma by UHPLC-MS/MS: The Assessment of Predicable Bioequivalence of In-vitro Dissolution Condition

Wang Y., Wang R., Wang H., Liu R., Bi K., Li Q.

Abstract

Background:Essential hypertension is a common clinical disease and a risk factor for cardiovascular and cerebrovascular diseases. Olmesartan medoxomil, amlodipine, and hydrochlorothiazide are commonly used antihypertensive drugs. The aim of this study was to establish a robust UPLC-MS/MS method for the simultaneous determination of olmesartan medoxomil, amlodipine, and hydrochlorothiazide in dog plasma. At the same time, the in vivo and in vitro release studies were conducted, and a preliminary in vitro-in vivo correlation (IVIVC) evaluation was performed.

Methods:The bioequivalence experiment was conducted with a double-crossed design. Three major components were extracted and analyzed by UHPLC-MS/MS. With the MRM scan, olmesartan and amlodipine were quantified by fragment conversion (m/z 447.10→190.10) and (m/z 408.95→294.00) under positive ESI mode, while hydrochlorothiazide was quantified with fragment conversion (m/z 295.90→268.90) under negative ESI mode. The in vitro release studies were performed using a USP paddle, and the dissolution medium was chosen from pH 6.0 to pH 6.8 according to the BCS classification of compounds. The IVIVC was calculated using the Wagner-Nelson equation.

Results:The linear ranges of olmesartan, amlodipine, and hydrochlorothiazide in the plasma were 5.0-2500, 0.1-50, and 3.0-1500 ng/mL, respectively. All accuracies were within 3.8% of the target values, and the findings revealed that intra-day and inter-day accuracies were less than 12.1%. Moreover, the recoveries exceeded 88.3%, the matrix effect tests were positive, and the stability tests were positive. With the establishment of correlation, the distinguishable dissolution condition (pH 6.8) was selected as the predictable condition.

Conclusion:The established method was suitable for the preclinical pharmacokinetic study of tripartite drugs with strong specificity and high sensitivity. Through the evaluation of IVIVC, the connection between in vivo and in vitro drug testing was initially established.

Current Pharmaceutical Design. 2024;30(32):2574-2585
pages 2574-2585 views