Pharmaceutical Applications and Therapeutic Mechanisms of Substances from Plant Origin

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Targeting and Design".

Deadline for manuscript submissions: 31 October 2025 | Viewed by 1092

Special Issue Editors


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Guest Editor
Department of Biology, Faculty of Pharmacy, Medical University of Varna, 9000 Varna, Bulgaria
Interests: pharmacognosy; phytochemistry; phytotherapy
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
1. Department of Pharmacognosy and Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria
2. Research Institute, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria
Interests: nutrition; phytochemistry; phytotherapy; pharmaceutical analysis
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Department of Pharmacology, Toxicology and Pharmacotherapy, Faculty of Pharmacy, Medical University of Varna, 9000 Varna, Bulgaria
Interests: pharmacology; toxicology
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Guest Editor
Department of Pharmaceutical Technologies, Faculty of Pharmacy, Medical University of Varna, 9000 Varna, Bulgaria
Interests: drug stability; silver nanoparticles; polymeric nanoparticles; pharmaceutical analysis; transdermal and mucosal drug permeation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Plants have been a significant source of medicinal compounds for centuries, offering a wide range of bioactive substances with substantial pharmacological potential. Traditional medicine systems in various cultures have long relied on plant-derived medicines, many of which have been subsequently validated by scientific research. The diverse chemical composition of plants, including alkaloids, terpenes, terpenoids, and polyphenols, contributes to their wide range of therapeutic effects, such as anti-inflammatory, antimicrobial, anticancer, antioxidant, and neuroprotective properties, among many others.

As modern medicine faces challenges such as antibiotic resistance, chronic diseases, and adverse drug reactions, the scientific community is particularly interested in the search for new plant-based pharmaceuticals. Advances in phytochemistry, molecular biology, and pharmacology have further improved plant-derived compounds’ identification, isolation, and modification, paving the way for new therapeutic agents.

The Special Issue of Pharmaceutics welcomes the submission of manuscripts focused on drug delivery systems, absorption, distribution, metabolism, excretion (ADME), pharmacokinetics, pharmacodynamics, and therapeutic mechanisms of substances from plant origin.

The Special Issue of Pharmaceuticals also welcomes manuscripts focusing on the analysis of cellular and molecular mechanisms of natural compounds or characterized extracts.

You may choose our Joint Special Issue in Pharmaceuticals.

Dr. Iliya Zhelev Slavov
Dr. Stanislava Ivanova
Dr. Nadezhda Hvarchanova
Dr. Nadezhda Ivanova
Guest Editors

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Keywords

  • natural substances
  • phytotherapy
  • phytochemistry
  • chromatography
  • pharmacokinetics
  • pharmacodynamics
  • drug delivery

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Published Papers (1 paper)

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Review

69 pages, 3282 KB  
Review
Formulation Strategies for Immunomodulatory Natural Products in 3D Tumor Spheroids and Organoids: Current Challenges and Emerging Solutions
by Chang-Eui Hong and Su-Yun Lyu
Pharmaceutics 2025, 17(10), 1258; https://doi.org/10.3390/pharmaceutics17101258 - 25 Sep 2025
Viewed by 795
Abstract
Background/Objectives: Natural products exhibit significant immunomodulatory potential but face severe efficacy loss in three-dimensional (3D) tumor models. This review comprehensively examines the penetration–activity trade-off and proposes integrated strategies for developing effective natural product-based cancer immunotherapies. Methods: We analyzed formulation strategies across three natural [...] Read more.
Background/Objectives: Natural products exhibit significant immunomodulatory potential but face severe efficacy loss in three-dimensional (3D) tumor models. This review comprehensively examines the penetration–activity trade-off and proposes integrated strategies for developing effective natural product-based cancer immunotherapies. Methods: We analyzed formulation strategies across three natural product categories (hydrophobic, macromolecular, stability-sensitive), evaluating penetration enhancement versus activity preservation in spheroids, organoids, and advanced 3D platforms. Results: Tumor spheroids present formidable barriers: dense extracellular matrix (33-fold increased fibronectin), pH gradients (7.4 → 6.5), and extreme cell density (6 × 107 cells/cm3). While nanoparticles, liposomes, and cyclodextrins achieve 3–20-fold penetration improvements, biological activity frequently declines through conformational changes, incomplete release (10–75%), and surface modification interference. Critically, immune cells remain peripheral (30–50 μm), questioning deep penetration pursuit. Patient-derived organoids display 68% predictive accuracy, while emerging vascularized models unveil additional complexity. Food and Drug Administration (FDA) Modernization Act 2.0 enables regulatory acceptance of these advanced models. Conclusions: Effective therapeutic outcomes depend on maintaining immunomodulatory activity in peripherally-located immune cell populations rather than achieving maximum tissue penetration depth. Our five-stage evaluation framework and standardization protocols guide development. Future priorities include artificial intelligence-driven optimization, personalized formulation strategies, and integration of multi-organ platforms to bridge the critical gap between enhanced delivery and therapeutic efficacy. Full article
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