Pharmaceutics

19 pages, 3059 KiB

Open AccessArticle

Increased Cellular Uptake of ApoE3- or c(RGD)-Modified Liposomes for Glioblastoma Therapy Depending on the Target Cells

by Larissa J. Lubitz, Moritz P. Haffner, Harden Rieger and Gero Leneweit

Pharmaceutics 2024, 16(9), 1112; https://doi.org/10.3390/pharmaceutics16091112 (registering DOI) - 23 Aug 2024

As effective treatment of glioblastoma is still an unmet need, targeted delivery systems for efficient treatment are of utmost interest. Therefore, in this paper, surface modifications with a small peptide c(RGD) or physiological protein (ApoE3) were investigated. Cellular uptake in murine endothelial cells (bEnd.3) and different glioma cells (human U-87 MG, rat F98) was tested to elucidate possible differences and to correlate the uptake to the receptor expression. Different liposomal formulations were measured at 1 and 3 h for three lipid incubation concentrations. We calculated the liposomal uptake saturation S and the saturation half-time t_1/2. An up to 9.6-fold increased uptake for ApoE3-modified liposomes, primarily in tumor cells, was found. Contrarily, c(RGD) liposomes showed a stronger increase in uptake in endothelial cells (up to 40.5-fold). The uptake of modified liposomes revealed enormous differences in S and t_1/2 when comparing different tumor cell lines. However, for ApoE3-modified liposomes, we proved comparable saturation values (~25,000) for F98 cells and U-87 MG cells despite a 6-fold lower expression of LRP1 in F98 cells and a 5-fold slower uptake rate. Our findings suggest that cellular uptake of surface-modified liposomes depends more on the target structure than the ligand type, with significant differences between cell types of different origins. Full article

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16 pages, 2634 KiB

Open AccessArticle

Derivatives of Pyrimidine Nucleosides Affect Artificial Membranes Enriched with Mycobacterial Lipids

by Olga S. Ostroumova, Svetlana S. Efimova, Polina D. Zlodeeva, Liudmila A. Alexandrova, Dmitry A. Makarov, Elena S. Matyugina, Vera A. Sokhraneva, Anastasia L. Khandazhinskaya and Sergey N. Kochetkov

Pharmaceutics 2024, 16(9), 1110; https://doi.org/10.3390/pharmaceutics16091110 (registering DOI) - 23 Aug 2024

Abstract

The mechanisms of action of pyrimidine nucleoside derivatives on model lipid membranes of various compositions were studied. A systematic analysis of the tested agents’ effects on the membrane physicochemical properties was performed. Differential scanning microcalorimetry data indicated that the ability of nucleoside derivatives to disorder membrane lipids depended on the types of nucleoside bases and membrane-forming lipids. The 5′-norcarbocyclic uracil derivatives were found to be ineffective, while N⁴-alkylcytidines demonstrated the most pronounced effects, significantly decreasing the dipalmitoylphosphocholine melting temperature and cooperativity of phase transition. The elongation of hydrophobic acyl radicals potentiated the disordering action of N⁴-alkylcytidines, while an increase in hydrophilicity due to replacing deoxyribose with ribose inhibited this effect. The ability of compounds to form transmembrane pores was also tested. It was found that 5-alkyluridines produced single, ion-permeable pores in phosphatidylglycerol membranes, and that methoxy-mycolic acid and trehalose monooleate potentiated the pore-forming activity of alkyloxymethyldeoxyuridines. The results obtained open up perspectives for the development of innovative highly selective anti-tuberculosis agents, which may be characterized by a low risk of developing drug resistance due to the direct action on the membranes of the pathogen. Full article

(This article belongs to the Special Issue Bioactive Agents for the Treatment against Tuberculosis)

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21 pages, 2063 KiB

Open AccessArticle

Synergistic Strategies in Prostate Cancer Therapy: Electrochemotherapy and Electromagnetic Hyperthermia

by Sayma Vizcarra-Ramos, Andrea Molina-Pineda, Abel Gutiérrez-Ortega, Sara E. Herrera-Rodríguez, Adriana Aguilar-Lemarroy, Luis F. Jave-Suárez, Zaira López, Mario E. Cano and Rodolfo Hernández-Gutiérrez

Pharmaceutics 2024, 16(9), 1109; https://doi.org/10.3390/pharmaceutics16091109 (registering DOI) - 23 Aug 2024

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Abstract

Prostate cancer is a significant global health problem, being the second most common cancer and the fifth leading cause of death in men worldwide. Standard chemotherapy, though effective, often lacks selectivity for tumor cells, resulting in dose-limiting side effects. To address this, innovative biomedical approaches such as electrochemotherapy and electromagnetic hyperthermia have emerged. Electrochemotherapy improves drug delivery by facilitating electroporation, thereby increasing intracellular concentrations of chemotherapeutic agents. This approach reduces dosages and associated adverse effects. Meanwhile, electromagnetic hyperthermia raises the temperature of tumor cells, enhancing their sensitivity to chemotherapy. While previous research has demonstrated the inhibitory effects of magnetic hyperthermia on prostate cancer cell growth both in vitro and in vivo, and its synergy with chemotherapy has shown enhanced tumor remission, limited studies have focused on electrochemotherapy alone or in combination with hyperthermia in prostate cancer models. This study aims to assess the synergistic effects of electromagnetic hyperthermia, with superparamagnetic iron oxide nanoparticles (SPIONs) and electrochemotherapy, with electroporation and the chemotherapeutic drugs bleomycin and cisplatin, on the prostate cancer-derived cell line DU-145/GFP and prostate-derived cell line RWPE-1. Results indicate enhanced cytotoxicity with both treatments (bleomycin and cisplatin) by adding electroporation, demonstrating a particularly pronounced effect with bleomycin. Combining electroporation with hyperthermia significantly augments cytotoxicity. Moreover, electroporation effectively reduced the time of exposure to electromagnetic hyperthermia while magnifying its cytotoxic effects. Future research in in vivo trials may reveal additional insights into the combined effects of these therapies. Full article

(This article belongs to the Special Issue Metal and Carbon Nanomaterials for Pharmaceutical Applications)

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13 pages, 2701 KiB

Open AccessArticle

Metronidazole Modified-Release Therapy Using Two Different Polymeric Systems Gels or Films: Clinical Study for the Treatment of Periodontitis

by Mônica Danielle Ribeiro Bastos, Tatiane Cristina Dotta, Beatriz Roque Kubata, Cássio do Nascimento, Ana Paula Macedo, Fellipe Augusto Tocchini de Figueiredo, Millena Mangueira Rocha, Maria Paula Garofo Peixoto, Maíra Peres Ferreira, Osvaldo de Freitas and Vinicius Pedrazzi

Pharmaceutics 2024, 16(9), 1108; https://doi.org/10.3390/pharmaceutics16091108 (registering DOI) - 23 Aug 2024

Viewed by 141

Abstract

This study evaluated the efficacy of semisolid systems (gels) and films containing a combination of metronidazole (MTZ) and metronidazole benzoate after scaling and root-planing (SRP) for periodontitis. In total, 45 patients with stage I or II periodontitis were enrolled and divided into 3 groups: 1—SRP—control; 2—SRP + Film with MTZ; 3—SRP + Gel with MTZ. The pH of gingival crevicular fluid (GCF) before/after treatments, MTZ concentrations, and drug release using high-performance liquid chromatography were investigated. The effects were evaluated by longitudinal monitoring of clinical parameters (probing depth—PD, clinical attachment level—CAL, and bleeding on probing—BP). MTZ and MTZ-benzoate concentrations in the periodontal pocket and pH showed no statistical difference after application. SRP + Gel presented the lowest CAL values. For SRP + Film and SRP + Gel, higher PD values were observed at T0 compared to all groups. A relevant reduction in BP was observed in SRP + Film and SRP + Gel groups at all times compared to T0. Both therapies improved periodontal health compared to SRP alone, reducing PD and BP, and increasing CAL for the gel group, suggesting they are promising for periodontal disease treatment. Full article

(This article belongs to the Special Issue Advanced Strategies for Sublingual and Buccal Drug Delivery)

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Pharmaceutics, Volume 16, Issue 9 (September 2024) – 4 articles

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