Vol 25, No 3 (2024)

Biotechnology

Pegylation, a Successful Strategy to Address the Storage and Instability Problems of Blood Products: Review 2011-2021

Mehrizi T., Mirzaei M., Ardestani M.

Abstract

Conjugation of polyethylene glycol (PEGylation) to blood proteins and cells has emerged as a successful approach to address some of the issues attributed to the storage of blood products, including their short half-life and instability. In this regard, this review study aims to compare the influence of different PEGylation strategies on the quality of several blood products like red blood cells (RBCs), platelets, plasma proteins, i.e., albumin, coagulation factor VIII, and antibodies. The results indicated that conjugating succinimidyl carbonate methoxyPEG (SCmPEG) to platelets could improve blood transfusion safety by preventing these cells from being attached to low-load hidden bacteria in blood products. Moreover, coating of 20 kD succin- imidyl valerate (SVA)-mPEG to RBCs was able to extend the half-life and stability of these cells during storage, as well as immune camouflage their surface antigens to prevent alloimmunisation. As regards albumin products, PEGylation improved the albumin stability, especially during sterilization, and there was a relationship between the molecular weight (MW) of PEG molecules and the biological half-life of the conjugate. Although coating antibodies with short-chain PEG molecules could enhance their stabilities, these modified proteins were cleared from the blood faster. Also, branched PEG molecules enhanced the retention and shielding of the fragmented and bispecific antibodies. Overall, the results of this literature review indicate that PEGylation can be considered a useful tool for enhancing the stability and storage of blood components.

Current Pharmaceutical Biotechnology. 2024;25(3):247-267
pages 247-267 views

Lipid Nanocapsule: A Novel Approach to Drug Delivery System Formulation Development

Kumar P., Yadav N., Chaudhary B., Umakanthan S., Chattu V., Kazmi I., Al-Abbasi F., Alzarea S., Afzal O., Altamimi A., Gupta G., Gupta M.

Abstract

Nanocapsules are polymeric nanoparticles encased in a polymeric coating composed of a predominantly non-ionic surfactant, macromolecules, phospholipids, and an oil core. Lipophilic drugs have been entrapped using various nanocarriers, including lipid cores, likely lipid nanocapsules, solid lipid nanoparticles, and others. A phase inversion temperature approach is used to create lipid nanocapsules. The PEG (polyethyleneglycol) is primarily utilised to produce nanocapsules and is a critical parameter influencing capsule residence time. With their broad drug-loading features, lipid nanocapsules have a distinct advantage in drug delivery systems, such as the capacity to encapsulate hydrophilic or lipophilic pharmaceuticals. Lipid nanocapsules, as detailed in this review, are surface modified, contain target-specific patterns, and have stable physical and chemical properties. Furthermore, lipid nanocapsules have target-specific delivery and are commonly employed as a marker in the diagnosis of numerous illnesses. This review focuses on nanocapsule synthesis, characterisation, and application, which will help understand the unique features of nanocapsules and their application in drug delivery systems.

Current Pharmaceutical Biotechnology. 2024;25(3):268-284
pages 268-284 views

Changing Trends Towards Herbal Supplements: An Insight into Safety and Herb-drug Interaction

Rasheed H., Ahmed S., Sharma A.

Abstract

Herbs have been used as sustenance and medicine for a very long time, often in conjunction with other prescribed medications. Even though they are thought to be natural and secure, many of these herbs can interact with other medications and cause potentially dangerous adverse effects or decrease the benefits of the medication. The complex and diverse pharmacological functions carried out by the active ingredients in herbs unavoidably alter the pharmacokinetics of chemical drugs when administered in vivo. Drug transporter expression has a direct impact on how medications are absorbed, distributed, metabolized, and excreted in living organisms. Changes in substrate pharmacokinetics can affect the effectiveness and toxicity of a drug when the active ingredients of a herb inhibit or stimulate the expression of transporters. By reviewing published clinical and preclinical studies, this review aims to raise awareness of herbdrug interactions and discuss their evidence-based mechanisms and clinical consequences. More clinical information on herb-drug interactions is required to make choices regarding patient safety as the incidence and severity of herb-drug interactions are rising due to an increase in the use of herbal preparations globally.This review seeks to increase understanding of herb-drug interactions and explore their evidence-based mechanisms and clinical implications by reviewing published clinical and preclinical studies. The incidence and severity of herb-drug interactions are on the rise due to an increase in the use of herbal preparations worldwide, necessitating the need for more clinical data on these interactions in order to make decisions regarding patient safety. Healthcare workers and patients will become more alert to potential interactions as their knowledge of pharmacokinetic herb-drug interactions grows. The study's objective is to raise readers' awareness of possible interactions between herbal supplements and prescription medications who regularly take them.

Current Pharmaceutical Biotechnology. 2024;25(3):285-300
pages 285-300 views

Drug Repositioning Using Computer-aided Drug Design (CADD)

Roy A., Nagaprasad N., Aruna M., Tesfaye J., Badassa B., Krishnaraj R., Rawat S., Subramaniam K., Subramanian S., Subbarayan S., Dhanabalan S., Chidambaram S.K., Stalin B.

Abstract

Drug repositioning is a method of using authorized drugs for other unusually complex diseases. Compared to new drug development, this method is fast, low in cost, and effective. Through the use of outstanding bioinformatics tools, such as computer-aided drug design (CADD), computer strategies play a vital role in the re-transformation of drugs. The use of CADD's special strategy for target-based drug reuse is the most promising method, and its realization rate is high. In this review article, we have particularly focused on understanding the various technologies of CADD and the use of computer-aided drug design for target-based drug reuse, taking COVID-19 and cancer as examples. Finally, it is concluded that CADD technology is accelerating the development of repurposed drugs due to its many advantages, and there are many facts to prove that the new ligand-targeting strategy is a beneficial method and that it will gain momentum with the development of technology.

Current Pharmaceutical Biotechnology. 2024;25(3):301-312
pages 301-312 views

Volatile Oil Containing Plants as Phytopharmaceuticals to Treat Psoriasis: A Review

Vyas P., Wagh S., Kalaskar M., Patil K., Sharma A., Kazmi I., Al-Abbasi F., Alzarea S., Afzal O., Altamimi A., Gupta G., Patil C.

Abstract

Introduction:Psoriasis is a chronic skin condition caused by an autoimmune response that accelerates the life cycle of skin cells, resulting in the characteristic symptoms of scaling, inflammation, and itching.

Methods:Palliative treatment options for psoriasis often prioritize the use of volatile oils. These oils contain monoterpenes, sesquiterpenes, and phenylpropanoids that are intricately linked to the molecular cascades involved in the pathogenesis and symptoms of psoriasis. To evaluate the antipsoriatic efficacy of volatile oils and their components, we conducted a systematic review of scientific studies. Our literature search encompassed various online databases, including PubMed, BIREME, SCIELO, Open Grey, Scopus, and ScienceDirect. The selected studies included experimental in vitro/in vivo assessments as well as clinical studies that examined the potential of volatile oils and their extracts as antipsoriatic agents. We excluded conference proceedings, case reports, editorials, and abstracts. Ultimately, we identified and evaluated a total of 12 studies for inclusion in our analysis.

Results:The data collected, compiled, and analyzed strongly support the interaction between volatile oils and their constituents with the key molecular pathways involved in the pathogenesis of psoriasis and the development of its symptoms. Volatile oils play a significant role in the palliative treatment of psoriasis, while their chemical constituents have the potential to reduce the symptoms and recurrence of this condition.

Conclusion:The current review highlights that the constituents found in volatile oils offer distinct chemical frameworks that can be regarded as promising starting points for the exploration and development of innovative antipsoriatic agents.

Current Pharmaceutical Biotechnology. 2024;25(3):313-339
pages 313-339 views

Synthesis, Characterization and Biosafety Evaluation of Hollow Gold Nanospheres

Zhang L., Zhang X., Hu Y., You J.

Abstract

Objectives:In order to assess the biosafety of HAuNS using zebrafish models and the cancer cell lines HepG2, HEK293, and A549, this study prepared HAuNS in a variety of sizes and alterations.

Methods:By oxidizing cobalt nanoparticles encased in gold shells, HAuNS were created. In the meantime, PEG- and PEI-coated HAuNS were created. The diameters of the HAuNS that were produced were 30~40 nm, 50~60 nm, and 70~80 nm. MTT assay was used to assess the toxicity of HAuNS on HepG2, HEK293, and A549 cells. For the investigation of their toxicities, HAuNS (50~60 nm) of various concentrations were incubated with zebrafish embryos. Then, cell death was determined using acridine orange staining.

Results:In a cell line model, it was demonstrated that purified HAuNS exhibit lower toxicity than unpurified HAuNS. Meanwhile, it was discovered that surface-modified HAuNS was less hazardous than unmodified HAuNS. Unpurified HAuNS (50–60 nm) exposure to embryos caused deformity and increased mortality. Moreover, embryos exposed to HAuNS displayed an increase in cell death, showing that HAuNS can put zebrafish under physiological stress.

Conclusion:The possible toxicity of HAuNS is now more understood thanks to this investigation. The details could improve our comprehension of the nanotoxicity of medication delivery systems. Comparing HAuNS (50~60nm) to the other two particle sizes, its toxicity was quite low. Compared to unpurified HAuNS, purified HAuNS displayed less toxicity. Comparing PEI-HAuNS and HAuNS to PEG-HAuNS, cytotoxicity was found to be lower. Our data support the use of pure HAuNS, HAuNS-PEG, and HAuNS (50~60nm) as possible photothermal conductors when seen as a whole.

Current Pharmaceutical Biotechnology. 2024;25(3):340-349
pages 340-349 views

Novel Leflunomide Analog, UTLOH-4e, Ameliorates Gouty Arthritis Induced by Monosodium Urate Via NF-κB/NLRP3 Signaling Pathway

Yuan T., Chen S., Yin Y., Shaw J., Zeng J., Li L., Song L., Zhang Y., Yin Z., Zhao J.

Abstract

Background:Gouty arthritis (GA) is a common form of inflammatory arthritis caused by intra-articular deposition of monosodium urate (MSU) crystals; however, there is a tremendous lack of safe and effective therapy in the clinic.

Objective:The goal of this work was to investigate a novel leflunomide analogue, N-(2,4- dihydroxyphenyl)-5-methyl-1,2-oxazole-3-carboxamide (UTLOH-4e), for its potential to prevent/ treat gouty arthritis.

Methods:In this study, the anti-inflammatory activity of UTLOH-4e was evaluated by MSUinduced GA model in vivo and in vitro, and the molecular docking test was applied to estimate the affinity of UTLOH-4e/UTL-5g/b for MAPKs, NF-κB, and NLRP3.

Results:In vitro, UTLOH-4e (1~100 µM) treatment inhibited the inflammatory reaction with no obvious cytotoxicity in PMA-induced THP-1 macrophages exposed to MSU crystals for 24 h, involving the prominent decreased production and gene expression of IL-1β, TNF-α, and IL-6. Western blot analyses demonstrated that UTLOH-4e (1~100 µM) significantly suppressed the activation of NLRP3 inflammasomes, NF-κB, and MAPK pathways. Furthermore, the data from the experiment on gouty rats induced by intra-articular injection of MSU crystal confirmed that UTLOH-4e markedly ameliorated rat paw swelling, articular synovium inflammation and reduced the concentration of IL-1β and TNF-α in serum through down-regulating NLRP3 protein expression.

Conclusion:These results manifested that UTLOH-4e ameliorates GA induced by MSU crystals, which contributes to the modulation of NF-κB/ NLRP3 signaling pathway, suggesting that UTLOH- 4e is a promising and potent drug candidate for the prevention and treatment of gouty arthritis.

Current Pharmaceutical Biotechnology. 2024;25(3):350-364
pages 350-364 views

Formulation, Evaluation and Optimization of Antimicrobial Potential of Herbal Cream Containing Allium sativum, Moringa oleifera Extracts and Thymus vulgaris Oil

Sheikh M., Khan H., Khan M., Sharif A.

Abstract

Background:Herbal preparations can be formed by combining several plant classes. One possible explanation for the effectiveness of combined medications is that the various mixtures with different mechanisms may add up to produce a more comprehensive therapeutic effect.

Objective:This study aims to investigate the synergistic antibiotic potential of a cream containing three natural herbal extracts: Allium sativum, Moringa oleifera, and Thymus vulgaris. The efficacy of combining these plant extracts was compared to that of a standard antibiotic formulation (Polyfax).

Methods:The herbal cream was formulated by using aqueous extracts of garlic (Allium sativum), moringa (Moringa oleifera) and essential oil of thyme (Thymus vulgaris). The study aimed to explore the therapeutic potential of these extracts against bacteria. P. aeruginosa, B. subtilis, E. coli, S. aureus, and S. pneumonia are commonly found in fresh wounds.

Results:The results showed that garlic extract (5%) had the highest zone of inhibition, 14.26 ± 0.05 mm, and a combination of garlic (5%) and thyme (2%) exhibited a significant synergistic effect, with a 23.5 ± 0.05 mm zone of inhibition. High-performance liquid chromatography analysis revealed the presence of allicin, quercetin and thymol as potential therapeutic phytoconstituents. The formulated herbal cream had a soft texture, was easily spreadable, and had better stability and absorption than the standard polyfax. The topical application of the cream did not cause any skin reaction or allergy in mice. The in vivo wound healing effect of the herbal cream was investigated on an abrasion model of albino mice, and the results showed that the treatment group (46 ± 16.31%) had significant wound healing potential compared to the standard (64 ± 17.49%) and control groups (18 ± 3.74%).

Conclusion:The formulated herbal cream was a better alternative to standard therapy, exhibiting promising healing and antimicrobial effects with significant compatibility and safety profile.

Current Pharmaceutical Biotechnology. 2024;25(3):365-383
pages 365-383 views