فهرست مطالب

Pharmaceutical Sciences
Volume:31 Issue: 1, Jan 2025

  • تاریخ انتشار: 1403/10/27
  • تعداد عناوین: 10
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  • Kimiya Jouyban, Behrouz Seyfinejad, Ahmadreza Dehpour, Abolghasem Jouyban * Pages 1-2
  • Parikshit Roychowdhury, Indhumathi Thirugnanasambandham, Anindita De, Mirunalini Gobinath, Samanwita Khanra, Veera Venkata Satyanarayana Reddy Karri, Nihar Ranjan Bhuyan *, Gowthamrajan Kuppusamy * Pages 3-21

    TRAIL or tumor necrosis factor-related apoptosis-inducing ligand has been one of the major frontiers for the chemotherapeutic approach to treating carcinogenesis. Despite the emergence of TRAIL resistance cancer cell lines, it has been extensively studied for its unique property to induce apoptosis and provide specificity to any other conjugated chemotherapeutic agent. TRIAL highly reduces the dose and increases specific and targeted action against the cancer cells. It is a specific agonist for the death receptors DR4 and DR5 present on the cancer cell surface. Normal cells have more expression of decoy type of death receptors, which makes the use of TRAIL safer for regular cells. The TRAIL-drug conjugate systems have been under the radar due to their possible high synergistic potential and may open the door for the future cancer-specific targeted treatment frontier. This current study was conducted with a particular aim to provide a concise and simple amalgamation of current scenarios of different conjugations of this molecule along with various other molecules, RNAs, ligands, and anticancer drugs. Along with possible delivery systems of TRIAL that can have a significant future and the promise that is held by this particular way of cancer combinational chemotherapy with special interest in colorectal cancer.

    Keywords: Colorectal Cancer, Death Receptors, Drug Conjugates, TNF, TRAIL
  • Mostafa Amirinejad, Atoosa Haghighizadeh, Leila Etemad, Omid Rajabi Pages 22-42

    The follicular route has been explored for both topical and systemic drug delivery but its application is challenged by different limitations such as sebum flow and size-selectivity. Vesicular carriers like liposomes, niosomes, invasomes, and transferosomes, which have shown promise in overcoming these barriers, have been explored in this review study. These vesicles improve follicular penetration of drugs, with deformable carriers performing better than conventional liposomes. Also, modifying liposomes using permeation enhancers has been introduced as another choice to enhance their follicular penetration. Vesicular systems have been primarily used to deliver drugs for treating alopecia, acne, and topical infections. They have also demonstrated potential in systemic delivery of antihypertensive drugs and insulin. Local hair massage and iontophoresis techniques further improve vesicle follicular penetration.

    Keywords: Invasome, Intrafollicular, Liposome, Niosome, Transferosome, Transfollicular
  • Fatemeh Yousefbeyk, Saeed Ghasemi Pages 43-64

    The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase (RTK) that initiates various signaling pathways resulting in processes such as gene expression, proliferation, angiogenesis, and inhibition of apoptosis. Dysregulation of EGFR signaling causes tumor development and metastasis. Therefore, targeting EGFR can be introduced as a promising way for cancer treatment. Angiogenesis, the formation and growth of new capillaries from pre-existing vasculature, is a key process in many physiological and pathological processes, including embryonic development, tissue growth, wound healing, cancer, rheumatoid arthritis, diabetic retinopathy, axon growth, and inflammatory diseases. Vascular endothelial growth factor receptors (VEGFRs), as receptor tyrosine kinases, especially VEGFR-2, have been introduced as the main mediators of angiogenesis. Therefore, VEGFR-2 inhibitors could be attractive agents for blocking angiogenesis and tumor growth. Due to the common downstream signaling pathways of EGFR and VEGFR-2, simultaneous inhibition of both receptor tyrosine kinases can be used as a valuable method in cancer therapy. Targeting the ATP-binding site of the tyrosine kinase domain using small molecules, either reversibly or irreversibly, is one way to inhibit EGFR and VEGFR-2. Different drugs with various scaffolds such as quinazoline (Vandetanib) and pyrimidine (Regorafenib) have been approved by the FDA for the treatment of various malignancies. Among them, the quinazoline skeleton is an attractive core with a wide range of activities. Vandetanib, a quinazoline-based EGFR/VEGFR-2 dual inhibitor, is an orally administered drug for the treatment of locally advanced or metastatic medullary thyroid cancer. Due to the limited number of multitarget kinases, as well as limitations in their clinical efficacy, adverse effects, and drug resistance, there is a vital need to introduce novel inhibitors with superior selectivity and efficacy compared to existing ones to overcome these challenges. Therefore, we reviewed the structure-activity relationship (SAR), EGFR/VEGFR-2 inhibitory activities, anticancer effects, and docking studies of synthesized quinazoline-based EGFR/VEGFR-2 dual inhibitors.

    Keywords: Dual Inhibitors, EGFR, Kinase, Quinazolines, Structure-Activity Relationship, VEGFR-2
  • Siavoush Dastmalchi, Aliakbar Alizadeh * Pages 65-73
    Background

    FGF7 is a potent cytoprotective and regenerative protein on the injured epithelial tissues, indicating its potential therapeutic effect in conditions such as mucositis, ulcerative colitis, and cutaneous wound formation induced by chemotherapy or radiotherapy. However, FGF7 low stability prevents its usability as a pharmaceutical product, necessitating the design and production of stable FGF7 mutants.

    Methods

    In the current study, bioinformatics and MD simulations approaches were used for identifying potential stable mutants of FGF7. For this, the model structure of FGF7 was constructed and subjected to MAESTROweb service to identify stability conferring mutations. The identified potential mutants of FGF7 were MD simulated in an explicit denaturant condition and their stabilities were evaluated. The complexes of FGF7 mutants with FGFR2 receptor were also examined to investigate the receptor binding ability of proposed mutants.

    Results

    Investigation of stability parameters showed that introducing A104S mutations in FGF7 may greatly improve its stability in urea solution. Calculation of binding energies indicated that A104S mutant interacts better then wild type FGF7 with the receptor. The structural stability and binding capability of A104S were comparable to that of A120C mutation, as an experimentally determined stability conferring mutation, which was used in whole process to indicate the validity of employed MD simulation for predicting the effect of mutation on FGF7 stability.

    Conclusion

    The results of current study showed that A104S mutant of FGF7 has a potential to be evaluated further for the purpose of presenting a therapeutic agent effective in conditions such as mucositis, ulcerative colitis, and cutaneous wound formation induced by chemotherapy or radiotherapy.

    Keywords: Explicit Denaturant Environment, FGF7, Maestroweb, Point Mutations, Stable Intermediate
  • Bijili Vijaya Laxmi, Darna Bhikshapathi*, Sailaja Rao Pages 74-88
    Background

    The use of Poly (lactic-co-glycolic acid) (PLGA) nanobubbles (NBs) aimed at functioning as a delivery system that encounter solubility issues for drugs like dabrafenib (DBF), which belonged to the Biopharmaceutical Classification System (BCS) class II category. These specially designed nanobubbles enhanced the drug’s solubility, stability, and bioavailability, thus improving the therapeutic effectiveness. Moreover, they offered controlled release characteristics and can potentially enhance drug delivery to tissues or cells, maximizing pharmacological results while reducing adverse effects.

    Methods

    PLGA NBs were formulated using solvent evaporation and optimized using a Box Behnken design considering process and formulation parameters. The NBs characterization includes particle size, drug loading, entrapment efficiency, in-vitro studies, haemolytic studies, Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimeter (DSC), stability studies, and as well as in-vivo studies in rats.

    Results

    The optimized nanobubbles (NBs) displayed a particle size (PS) of 190.6 ± 18.4 nm, zeta potential of -21 ± 4.2 mV, and polydispersity index (PDI) of 0.397 ± 0.096. With 87.21 ± 3.8% of entrapment efficiency (EE) and 26.29 ± 4.01% drug loading, in-vitro studies revealed a superior drug release (99%) with ultrasound versus plain drugs (20%). FTIR and DSC studies confirmed no drug-polymer interaction. Scanning Electron Microscopy (SEM) images displayed uniform spherical nanosized particles. Haemolytic activity demonstrated safety, and stability studies indicated no significant changes after 30 days. The nanobubbles exhibited increased Cmax (4.74) and AUC0-t (6.82), thereby promising an enhanced solubility, absorption, and extended half-life.

    Conclusion

    The current investigation showed that PLGA nanobubbles loaded with dabrafenib have a promising delayed release potential, which might make them a possible treatment alternative for breast cancer.

    Keywords: Box-Behnken Design, Chronic Myeloid Leukaemia, Dabrafenib, Nanobubbles
  • Abbas Moridnia, Leyla Hoseinitabar, Alireza Khosropanah, Ladan Mafakher, Marzieh Anaam, Babak Elyasi Far * Pages 89-95
    Background

    The rise of multi-drug-resistant bacteria seriously threatens human health. Some microorganisms can produce new antimicrobials that have effects on multidrug-resistant bacteria. On the other hand, halophilic bacteria show promise in producing novel bioactive antimicrobial compounds that could benefit drug development. This study aims to investigate the antimicrobial properties of halophilic bacteria recently isolated in soil samples from Shushtar City, Khuzestan Province, Iran.

    Methods

    In this research, saline soil samples were collected from the salty areas around Shushtar City. The soil sample was then cultured in an enriched culture medium, and in order to isolate the halophilic bacteria, they were cultured in a solid medium. The microorganisms were examined for the production of antimicrobial agents using the agar well diffusion method. Subsequently, the halophilic bacteria were identified through molecular analysis of the 16S rRNA method. The phylogenetic tree was constructed using Mega software through the neighbor-joining method.

    Results

    Twenty-two strains were isolated in this study. Strain E1, identified as Alkalihalobacillus sp, displayed antimicrobial activity against Enterococcus faecalis. The MIC and MBC of the Alkalihalobacillus extracts against Enterococcus faecalis were determined to be 25 µg/mL

    Conclusion

    This research highlights the potential therapeutic and preventive advantages of Alkalihalobacillus sp. extracts as antibacterial agents. This research report, for the first time,reveals that isolated Alkalihalobacillus in Iran has the ability to produce antimicrobial agents.The discovery and isolation of beneficial bacteria from natural sources could have significantimplications for future pharmaceutical and industrial applications.

    Keywords: Alkalihalobacillus Sp, Antimicrobial Activity, Enterococcus Faecalis, Human Pathogens, MIC
  • Riris Istighfari Jenie, Dhania Novitasari, Dyaningtyas Dewi Pamungkas Putri, Ratna Asmah Susidarti, Ikuko Nakamae, Noriko Yoneda-Kato, Jun-Ya Kato, Edy Meiyanto, * Pages 96-105
    Background

    Pentagamavunone-1 (PGV-1) is a promising cytotoxic chemotherapy agent in many cancer cells. However, due to its structure, PGV-1 is unstable and easily decomposed by light or high pH, causing decreased cytotoxic effect. Therefore, we developed a chemoprevention curcumin analog (CCA-1.1), a novel PGV-1 derivative which demonstrated improved solubility with similar antiproliferative activities toward breast and colon cancer cells. Our study intends to determine the antiproliferative effects based on the cellular and molecular mechanism of CCA-1.1 and PGV-1 in leukemic cells.

    Methods

    Using K-562 cells, CCA-1.1 and PGV-1 were tested for the cytotoxicity effect. Cell cycle analysis and ROS level were assessed by flow cytometry. Cells were stained with May–Grünwald–Giemsa and Hoechst to observe the mitotic phase arrest, while the X-Gal was selected to detect the senescence. The protein level of mitotic kinases (Aurora A, cyclinB1, and PLK1) was determined through Western blot.

    Results

    CCA-1.1 demonstrated an inhibitory effect on cell proliferation in K-562 cells following 96h treatment, with a GI50 value of 685 nM, akin to PGV-1 (GI50 score: 428 nM). Furthermore, this effect was found to be irreversible. It was shown that 1.2 μM CCA-1.1, similar to 0.8 μM PGV-1, induced cell cycle arrest specifically at mitosis after 24 h. CCA-1.1 induced cellular senescence and increased ROS production following 24 h incubation. A notable distinction between the two compounds lies in their respective effects on cell cycle progression. PGV-1 induced cell arrest at the prometaphase by 80% (p=0.0001), whereas CCA-1.1 was found to elicit around 20% of total cell arrest specifically at the metaphase (p=0.0035). Immunoblot experiments provided evidence that 24h treatment of CCA-1.1 tended to sustain the expression of p-cyclin B1, but PGV-1 led to an increase in the expression of p-cyclin B1 (p=0.0178) and p-PLK1 (p=0.0051).

    Conclusion

    The findings from our study provide evidence for the molecular mechanism on mitotic kinases of CCA-1.1 and PGV-1, resulting in the inhibition of the proliferation of leukemia cells during mitosis. Furthermore, CCA-1.1 induces mitotic catastrophe, leading to cellular death in K-562 cells.

    Keywords: Antimitotic Agents, Cellular Senescence, Chronic Myeloid Leukemia, Curcumin Analogs, M Phase Cell Cycle Arrest, Mitotic Index
  • Raha Kaviani * Pages 106-109
    Background

    Sensitivity in the determination of the drug concentration is critical in pharmaceutical analysis. This research investigates several approaches for determining two sensitivity parameters, the Limit of Detection (LOD) and the Limit of Quantification (LOQ), in the analysis of the drug concentration using High-Performance Liquid Chromatography (HPLC).

    Methods

    The study evaluates the FDA’s Lower Limit of Quantification (LLOQ) parameter, following global standards and quantitatively comparing sensitivity parameters for an established HPLC-UV method for the analysis of carbamazepine and phenytoin.

    Results

    The study found that the LOD and LOQ values obtained by different methods varied significantly. The signal-to-noise ratio (S/N) method provided the lowest LOD and LOQ values for both drugs, while the standard deviation of the response and slope (SDR) method resulted in the highest values. This highlights the variability in sensitivity depending on the method used.

    Conclusion

    The results show significant differences among calculated sensitivity values, emphasizing the influence of methodological variations on sensitivity values. It recommends following FDA criteria in chromatographic-based pharmaceutical analysis to improve the accuracy of drug concentration determination.

    Keywords: Analytical Method Validation, LOD, LOQ, Pharmaceutical Analysis, Sensitivity