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25 pages, 16091 KiB

Open AccessArticle

Syn-COM: A Multi-Level Predictive Synergy Framework for Innovative Drug Combinations

by Yinli Shi, Jun Liu, Shuang Guan, Sicun Wang, Chengcheng Yu, Yanan Yu, Bing Li, Yingying Zhang, Weibin Yang and Zhong Wang

Pharmaceuticals 2024, 17(9), 1230; https://doi.org/10.3390/ph17091230 - 18 Sep 2024

Abstract

Drug prediction and treatment using bioinformatics and large-scale modeling have emerged as pivotal research areas. This study proposes a novel multi-level collaboration framework named Syn-COM for feature extraction and data integration of diseases and drugs. The framework aims to explore optimal drug combinations [...] Read more.

Drug prediction and treatment using bioinformatics and large-scale modeling have emerged as pivotal research areas. This study proposes a novel multi-level collaboration framework named Syn-COM for feature extraction and data integration of diseases and drugs. The framework aims to explore optimal drug combinations and interactions by integrating molecular virtuality, similarity clustering, overlap area, and network distance. It uniquely combines the characteristics of Chinese herbal medicine with clinical experience and innovatively assesses drug interaction and correlation through a synergy matrix. Gouty arthritis (GA) was used as a case study to validate the framework’s reliability, leading to the identification of an effective drug combination for GA treatment, comprising Tamaricis Cacumen (S_i = 0.73), Cuscutae Semen (S_i = 0.68), Artemisiae Annuae Herba (S_i = 0.62), Schizonepetae Herba (S_i = 0.73), Gleditsiae Spina (S_i = 0.89), Prunellae Spica (S_i = 0.75), and Achyranthis Bidentatae Radix (S_i = 0.62). The efficacy of the identified drug combination was confirmed through animal experiments and traditional Chinese medicine (TCM) component analysis. Results demonstrated significant reductions in the blood inflammatory factors IL1A, IL6, and uric acid, as well as downregulation of TGFB1, PTGS2, and MMP3 expression (p < 0.05), along with improvements in ankle joint swelling in GA mice. This drug combination notably enhances therapeutic outcomes in GA by targeting key genes, underscoring the potential of integrating traditional medicine with modern bioinformatics for effective disease treatment. Full article

(This article belongs to the Special Issue The 20th Anniversary of Pharmaceuticals—How Artificial Intelligence Is Reshaping Pharmaceuticals Technology)

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23 pages, 2140 KiB

Open AccessArticle

Rational Function-Based Approach for Integrating Tableting Reduced-Order Models with Upstream Unit Operations: Dry Granulation Case Study

by Sunidhi Bachawala, Rexonni B. Lagare, Abigail B. Delaney, Zoltan K. Nagy, Gintaras V. Reklaitis and Marcial Gonzalez

Pharmaceuticals 2024, 17(9), 1158; https://doi.org/10.3390/ph17091158 - 31 Aug 2024

Viewed by 527

Abstract

We present a systematic and automatic approach for integrating tableting reduced-order models with upstream unit operations. The approach not only identifies the upstream critical material attributes and process parameters that describe the coupling to the first order and, possibly, the second order, but [...] Read more.

We present a systematic and automatic approach for integrating tableting reduced-order models with upstream unit operations. The approach not only identifies the upstream critical material attributes and process parameters that describe the coupling to the first order and, possibly, the second order, but it also selects the mathematical form of such coupling and estimates its parameters. Specifically, we propose that the coupling can be generally described by normalized bivariate rational functions. We demonstrate this approach for dry granulation, a unit operation commonly used to enhance the flowability of pharmaceutical powders by increasing granule size distribution, which, inevitably, negatively impacts tabletability by reducing the particle porosity and imparting plastic work. Granules of different densities and size distributions are made with a 10% w/w acetaminophen and 90% w/w microcrystalline cellulose formulation, and tablets with a wide range of relative densities are fabricated. This approach is based on product and process understanding, and, in turn, it is not only essential to enabling the end-to-end integration, control, and optimization of dry granulation and tableting processes, but it also offers insight into the granule properties that have a dominant effect on each of the four stages of powder compaction, namely die filling, compaction, unloading, and ejection. Full article

(This article belongs to the Special Issue The 20th Anniversary of Pharmaceuticals—How Artificial Intelligence Is Reshaping Pharmaceuticals Technology)

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24 pages, 12908 KiB

Open AccessArticle

Evolutionary Trend Analysis of Research on Immunotherapy for Brain Metastasis Based on Machine-Learning Scientometrics

by Xiaoqian Hu, Xinpei Deng, Jindong Xie, Hanqi Zhang, Huiting Zhang, Beibei Feng, Yutian Zou and Chuhuai Wang

Pharmaceuticals 2024, 17(7), 850; https://doi.org/10.3390/ph17070850 - 28 Jun 2024

Viewed by 1063

Abstract

Brain metastases challenge cancer treatments with poor prognoses, despite ongoing advancements. Immunotherapy effectively alleviates advanced cancer, exhibiting immense potential to revolutionize brain metastasis management. To identify research priorities that optimize immunotherapies for brain metastases, 2164 related publications were analyzed. Scientometric visualization via R [...] Read more.

Brain metastases challenge cancer treatments with poor prognoses, despite ongoing advancements. Immunotherapy effectively alleviates advanced cancer, exhibiting immense potential to revolutionize brain metastasis management. To identify research priorities that optimize immunotherapies for brain metastases, 2164 related publications were analyzed. Scientometric visualization via R software, VOSviewer, and CiteSpace showed the interrelationships among literature, institutions, authors, and topic areas of focus. The publication rate and citations have grown exponentially over the past decade, with the US, China, and Germany as the major contributors. The University of Texas MD Anderson Cancer Center ranked highest in publications, while Memorial Sloan Kettering Cancer Center was most cited. Clusters of keywords revealed six hotspots: ‘Immunology’, ‘Check Point Inhibitors’, ‘Lung Cancer’, ‘Immunotherapy’, ‘Melanoma’, ‘Breast Cancer’, and ‘Microenvironment’. Melanoma, the most studied primary tumor with brain metastases offers promising immunotherapy advancements with generalizability and adaptability to other cancers. Our results outline the holistic overview of immunotherapy research for brain metastases, which pinpoints the forefront in the field, and directs researchers toward critical inquiries for enhanced mechanistic insight and improved clinical outcomes. Moreover, governmental and funding agencies will benefit from assigning financial resources to entities and regions with the greatest potential for combating brain metastases through immunotherapy. Full article

(This article belongs to the Special Issue The 20th Anniversary of Pharmaceuticals—How Artificial Intelligence Is Reshaping Pharmaceuticals Technology)

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18 pages, 4761 KiB

Open AccessArticle

In Silico and In Vitro Studies on an Asymmetrical Porphyrin Derivative with Therapeutic Potential in Skin Disorders

by Andreea Mihaela Burloiu, Dragos Paul Mihai, Gina Manda, Dumitru Lupuliasa, Ionela Victoria Neagoe, Radu Petre Socoteanu, Mihaela Surcel, Laurentiu-Iliuta Anghelache, Laura Olariu, Cerasela Elena Gîrd and Rica Boscencu

Pharmaceuticals 2024, 17(6), 688; https://doi.org/10.3390/ph17060688 - 27 May 2024

Viewed by 1069

Abstract

For developing novel photosensitizers with therapeutic potential in non-malignant and malignant cutaneous disorders, the unsymmetrical porphyrin, 5-(2-hydroxy-3-methoxyphenyl)-10, 15, 20-tris-(4-carboxymethylphenyl) porphyrin, was evaluated in silico and in vitro. The cellular uptake of the investigated porphyrin and its ability to perform photodynamic therapy [...] Read more.

For developing novel photosensitizers with therapeutic potential in non-malignant and malignant cutaneous disorders, the unsymmetrical porphyrin, 5-(2-hydroxy-3-methoxyphenyl)-10, 15, 20-tris-(4-carboxymethylphenyl) porphyrin, was evaluated in silico and in vitro. The cellular uptake of the investigated porphyrin and its ability to perform photodynamic therapy were investigated in terms of the viability, proliferation, and necrosis of human HaCaT keratinocytes and human Hs27 skin fibroblasts, in correlation with the predictions regarding diffusion through cell membranes, ADMET profile (absorption, distribution, metabolism, elimination, toxicity), and potential pharmacological mechanism. Molecular docking and 250 ns molecular dynamics simulations revealed that P5.2 has the potential to form a relatively stable complex with the carbonic anhydrase IX catalytic site, the lowest predicted free energy of binding (MM/PBSA) being −39.097 kcal/mol. The results of the in vitro study showed that P5.2 is incorporated within 24 h in the investigated cells, especially in HaCaT keratinocytes, indicating its photosensitizing ability. Nevertheless, P5.2 does not exert significant cytotoxicity in “dark” conditions. In turn, PDT induced a decrease in the number of metabolically active HaCaT keratinocytes within 24 h, accompanied by a 4-fold increase in lactate dehydrogenase release, indicating its ability to perform PDT in human skin cells. The experimental results suggest that the asymmetrical porphyrin is a promising candidate theranostics agent for skin disorders. Full article

(This article belongs to the Special Issue The 20th Anniversary of Pharmaceuticals—How Artificial Intelligence Is Reshaping Pharmaceuticals Technology)

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23 pages, 11040 KiB

Open AccessArticle

Assessment of Some Unsymmetrical Porphyrins as Promising Molecules for Photodynamic Therapy of Cutaneous Disorders

by Andreea Mihaela Burloiu, Gina Manda, Dumitru Lupuliasa, Radu Petre Socoteanu, Dragos Paul Mihai, Ionela Victoria Neagoe, Laurentiu-Iliuta Anghelache, Mihaela Surcel, Mihai Anastasescu, Laura Olariu, Cerasela Elena Gîrd, Stefania Felicia Barbuceanu, Luis Filipe Vieira Ferreira and Rica Boscencu

Pharmaceuticals 2024, 17(1), 62; https://doi.org/10.3390/ph17010062 - 29 Dec 2023

Cited by 1 | Viewed by 1527

Abstract

In order to select for further development novel photosensitizers for photodynamic therapy in cutaneous disorders, three unsymmetrical porphyrins, namely 5-(4-hydroxy-3-methoxyphenyl)-10,15,20-tris-(4-acetoxy-3-methoxyphenyl) porphyrin (P2.2), 5-(2-hydroxy-5-methoxyphenyl)-10,15,20-tris-(4-carboxymethylphenyl) porphyrin (P3.2), and 5-(2,4-dihydroxyphenyl)-10,15,20-tris-(4-acetoxy-3-methoxyphenyl) porphyrin (P4.2), along with their fully symmetrical counterparts 5,10,15,20-tetrakis-(4-acetoxy-3-methoxyphenyl) porphyrin (P2.1) and 5,10,15,20-tetrakis-(4-carboxymethylphenyl) porphyrin (P3.1) were [...] Read more.

In order to select for further development novel photosensitizers for photodynamic therapy in cutaneous disorders, three unsymmetrical porphyrins, namely 5-(4-hydroxy-3-methoxyphenyl)-10,15,20-tris-(4-acetoxy-3-methoxyphenyl) porphyrin (P2.2), 5-(2-hydroxy-5-methoxyphenyl)-10,15,20-tris-(4-carboxymethylphenyl) porphyrin (P3.2), and 5-(2,4-dihydroxyphenyl)-10,15,20-tris-(4-acetoxy-3-methoxyphenyl) porphyrin (P4.2), along with their fully symmetrical counterparts 5,10,15,20-tetrakis-(4-acetoxy-3-methoxyphenyl) porphyrin (P2.1) and 5,10,15,20-tetrakis-(4-carboxymethylphenyl) porphyrin (P3.1) were comparatively evaluated. The absorption and fluorescence properties, as well as atomic force microscopy measurements were performed to evaluate the photophysical characteristics as well as morphological and textural properties of the mentioned porphyrins. The cellular uptake of compounds and the effect of photodynamic therapy on the viability, proliferation, and necrosis of human HaCaT keratinocytes, human Hs27 skin fibroblasts, human skin SCL II squamous cell carcinoma, and B16F10 melanoma cells were assessed in vitro, in correlation with the structural and photophysical properties of the investigated porphyrins, and with the predictions regarding diffusion through cell membranes and ADMET properties. All samples were found to be isotropic and self-similar, with slightly different degrees of aggregability, had a relatively low predicted toxicity (class V), and a predicted long half-life after systemic administration. The in vitro study performed on non-malignant and malignant skin-relevant cells highlighted that the asymmetric P2.2 porphyrin qualified among the five investigated porphyrins to be a promising photosensitizer candidate for PDT in skin disorders. P2.2 was shown to accumulate well within cells, and induced by PDT a massive decrease in the number of metabolically active skin cells, partly due to cell death by necrosis. P2.2 had in this respect a better behavior than the symmetric P.2.1 compound and the related asymmetric compound P4.2. The strong action of P2.2-mediated PDT on normal skin cells might be an important drawback for further development of this compound. Meanwhile, the P3.1 and P3.2 compounds were not able to accumulate well in skin cells, and did not elicit significant PDT in vitro. Taken together, our experiments suggest that P2.2 can be a promising candidate for the development of novel photosensitizers for PDT in skin disorders. Full article

(This article belongs to the Special Issue The 20th Anniversary of Pharmaceuticals—How Artificial Intelligence Is Reshaping Pharmaceuticals Technology)

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18 pages, 18183 KiB

Open AccessArticle

Biological Potential and Bioaccessibility of Encapsulated Curcumin into Cetyltrimethylammonium Bromide Modified Cellulose Nanocrystals

by Francisca Casanova, Carla F. Pereira, Alessandra B. Ribeiro, Pedro M. Castro, Ricardo Freixo, Eva Martins, Diana Tavares-Valente, João C. Fernandes, Manuela E. Pintado and Óscar L. Ramos

Pharmaceuticals 2023, 16(12), 1737; https://doi.org/10.3390/ph16121737 - 17 Dec 2023

Cited by 1 | Viewed by 1385

Abstract

Curcumin is a natural phenolic compound with important biological functions. Despite its demonstrated efficacy in vitro, curcumin biological activities in vivo are dependent on its bioaccessibility and bioavailability, which have been highlighted as a crucial challenge. Cetyltrimethylammonium bromide-modified cellulose nanocrystals (CNC-CTAB) have been [...] Read more.

Curcumin is a natural phenolic compound with important biological functions. Despite its demonstrated efficacy in vitro, curcumin biological activities in vivo are dependent on its bioaccessibility and bioavailability, which have been highlighted as a crucial challenge. Cetyltrimethylammonium bromide-modified cellulose nanocrystals (CNC-CTAB) have been shown to be effective in curcumin encapsulation, as they have the potential to enhance biological outcomes. This study evaluated the biological effects of curcumin encapsulated within CNC-CTAB structures, namely its antioxidant, anti-inflammatory and antimicrobial properties, as well as the release profile under digestion conditions and intestinal permeability. Encapsulated curcumin demonstrated antioxidant and anti-inflammatory properties, effectively reducing reactive oxygen species and cytokine production by intestinal cells. The delivery system exhibited antimicrobial properties against Campylobacter jejuni bacteria, further suggesting its potential in mitigating intestinal inflammation. The system showed the ability to protect curcumin from degradation and facilitate its interaction with the intestinal epithelium, highlighting the potential of CNC-CTAB as carrier to enhance curcumin intestinal biological functions. Full article

(This article belongs to the Special Issue The 20th Anniversary of Pharmaceuticals—How Artificial Intelligence Is Reshaping Pharmaceuticals Technology)

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12 pages, 2366 KiB

Open AccessArticle

Comparing the Performance of Raman and Near-Infrared Imaging in the Prediction of the In Vitro Dissolution Profile of Extended-Release Tablets Based on Artificial Neural Networks

by Dorián László Galata, Szilveszter Gergely, Rebeka Nagy, János Slezsák, Ferenc Ronkay, Zsombor Kristóf Nagy and Attila Farkas

Pharmaceuticals 2023, 16(9), 1243; https://doi.org/10.3390/ph16091243 - 1 Sep 2023

Cited by 2 | Viewed by 1426

Abstract

In this work, the performance of two fast chemical imaging techniques, Raman and near-infrared (NIR) imaging is compared by utilizing these methods to predict the rate of drug release from sustained-release tablets. Sustained release is provided by adding hydroxypropyl methylcellulose (HPMC), as its [...] Read more.

In this work, the performance of two fast chemical imaging techniques, Raman and near-infrared (NIR) imaging is compared by utilizing these methods to predict the rate of drug release from sustained-release tablets. Sustained release is provided by adding hydroxypropyl methylcellulose (HPMC), as its concentration and particle size determine the dissolution rate of the drug. The chemical images were processed using classical least squares; afterwards, a convolutional neural network was applied to extract information regarding the particle size of HPMC. The chemical images were reduced to an average HPMC concentration and a predicted particle size value; these were used as inputs in an artificial neural network with a single hidden layer to predict the dissolution profile of the tablets. Both NIR and Raman imaging yielded accurate predictions. As the instrumentation of NIR imaging allows faster measurements than Raman imaging, this technique is a better candidate for implementing a real-time technique. The introduction of chemical imaging in the routine quality control of pharmaceutical products would profoundly change quality assurance in the pharmaceutical industry. Full article

(This article belongs to the Special Issue The 20th Anniversary of Pharmaceuticals—How Artificial Intelligence Is Reshaping Pharmaceuticals Technology)

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Review

Jump to: Research

22 pages, 3781 KiB

Open AccessReview

A Bibliometric Analysis of 3D Printing in Personalized Medicine Research from 2012 to 2022

by Aile Xue, Wenjie Li, Wenxiu Tian, Minyue Zheng, Lan Shen and Yanlong Hong

Pharmaceuticals 2023, 16(11), 1521; https://doi.org/10.3390/ph16111521 - 26 Oct 2023

Cited by 2 | Viewed by 2516

Abstract

In recent years, the 3D printing of personalized drug formulations has attracted the attention of medical practitioners and academics. However, there is a lack of data-based analyses on the hotspots and trends of research in this field. Therefore, in this study, we performed [...] Read more.

In recent years, the 3D printing of personalized drug formulations has attracted the attention of medical practitioners and academics. However, there is a lack of data-based analyses on the hotspots and trends of research in this field. Therefore, in this study, we performed a bibliometric analysis to summarize the 3D printing research in the field of personalized drug formulation from 2012 to 2022. This study was based on the Web of Science Core Collection Database, and a total of 442 eligible publications were screened. Using VOSviewer and online websites for bibliometric analysis and scientific mapping, it was observed that annual publications have shown a significant growth trend over the last decade. The United Kingdom and the United States, which account for 45.5% of the total number of publications, are the main drivers of this field. The International Journal of Pharmaceutics and University College London are the most prolific and cited journals and institutions. The researchers with the most contributions are Basit, Abdul W. and Goyanes Alvaro. The keyword analysis concluded that the current research hotspots are “drug release” and “drug dosage forms”. In conclusion, 3D printing has broad application prospects in the field of personalized drugs, which will bring the pharmaceutical industry into a new era of innovation. Full article

(This article belongs to the Special Issue The 20th Anniversary of Pharmaceuticals—How Artificial Intelligence Is Reshaping Pharmaceuticals Technology)

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