Authors: Cristian Sandoval-Vásquez | F. Torrens | V. Souza-Mello | G. Castellano
Source: Frontiers in Pharmacology (article, 2026-04-10)
Field: Materials Science — Biomaterials

Editorial: Advances in novel pharmacotherapeutics and drug discovery: computational, experimental, translational, and clinical models, volume II This volume focuses on the rational design of medication delivery systems to improve efficacy and minimize off-target effects. Mao et al. (https://doi.org/10.3389/fimmu.2025.1680710) demonstrate a promising strategy in chemotherapy by chemically altering cabazitaxel with polycarboxylate conjugates (CTX-DTPA and CTX-TTHA) to markedly improve solubility and reduce systemic toxicities, such as myelosuppression and thymic damage.Nanotechnology remains a crucial component of these projects. Sandoval-Vásquez et al. (https://doi.org/10.3389/fphar.2025.1710176) provide a comprehensive evaluation indicating that PEG-PLGA nanoparticles significantly enhance cytotoxic activity and cellular uptake. A critical gap remains in bridging the gap between in vitro success and in vivo efficacy, as most studies currently lack complementary preclinical investigations addressing biodistribution and the complex stromal features of human tumors (https://doi.org/10.3389/fphar.2026.1723694; https://doi.org/10.3389/fphar.2025.1710176). Furthermore, there is a need to integrate real-time imaging into delivery platforms to evaluate theranostic applications and stimulus-responsive release mechanisms (https://doi.org/10.3389/fphar.2025.1710176).Crossing the blood-brain barrier (BBB) remains a major pharmacological challenge. Cheng and Kim (https://doi.org/10.3389/fphar.2025.1709259) explore the potential of intranasal administration to circumvent the BBB, presenting a non-invasive approach for iron chelators to treat neurodegenerative illnesses defined by brain iron overload.Beyond delivery, the field is increasingly moving toward precision neuropharmacology. Clinical and translational equity is also an important theme. Arias-Carrión and Ortega-Robles (https://doi.org/10.3389/fphar.2025.1725248) conducted a systematic study of motor fluctuations in Parkinson's disease, contrasting the great efficacy of current therapy highlighting disparities in drug accessibility across Latin America, where newer drugs often stay absent from national formularies.Translational efficiency is hindered by anatomical differences between rodents and humans, necessitating models that confirm if intranasal delivery can effectively redistribute iron in the human brain (https://doi.org/10.3389/fphar.2025.1709259). Additionally, the field requires a comprehensive atlas of receptor ensemble dynamics to move from global circuit suppression to targeted molecular calibration (https://doi.org/10.3389/fphar.2025.1697905).The progression of insulin therapy exemplifies a historical paradigm of pharmacological advancement. Recent studies persist in this direction, with Salagre et al. (https://doi.org/10.3389/fphar.2025.1633326) clarifying that melatonin, through MT2 receptors, can activate a thermogenic program in human myoblasts, indicating novel approaches for addressing "diabesity".The merging of computational and experimental methods has proved essential in the discovery of natural products. Iqbal et al. (https://doi.org/10.3389/fphar.2025.1713452) employed molecular dynamics and enzyme assays to identify components of Nardostachys jatamansi that surpass acarbose in blocking carbohydrate-hydrolyzing enzymes. In the cardiovascular domain, Xu et al. (https://doi.org/10.3389/fphar.2025.1699066) present an updated meta-analysis affirming that SGLT2 inhibitors confer early structural and functional advantages in heart remodeling post-myocardial infarction.There is a persistent need for the isolation and individual testing of computationally predicted natural compounds to validate virtual screening hits (https://doi.org/10.3389/fphar.2025.1713452)). Moreover, current clinical data on cardiac remodeling is limited by short follow-up periods, leaving the long-term sustainability of structural improvements and their translation into hard clinical endpoints unclear (https://doi.org/10.3389/fphar.2025.1699066).Enhancing existing pharmaceuticals by synergistic combinations can elevate the therapeutic index. Zárate et al. (https://doi.org/10.3389/fphar.2025.1692519) illustrate via preclinical models and a Phase 1 human study that the combination of pregabalin and thioctic acid yields synergistic alleviation of neuropathic pain while preserving a good safety profile. Gaps exist regarding the long-term sustainability of synergistic effects under chronic dosing and whether these results extend across both sexes (https://doi.org/10.3389/fphar.2025.1675015). In anesthesia, research must prioritize standardizing outcome definitions for emergence agitation and investigating post-discharge neurocognitive features, such as mood and focus capacity (https://doi.org/10.3389/fphar.2025.1681936).The articles in Volume II reflect a maturing drug discovery landscape where computational predictions are rigorously tested in experimental and clinical models. However, identifying several core gaps is essential for future progress: i) Oncology: Drug delivery ; Biodistribution ; Drug ; In vivo ; Clinical trial ; Fingolimod ; Nanomedicine ; Nasal administration Nanoparticle-Based Drug Delivery ; Nanoplatforms for cancer theranostics ; Protein Degradation and Inhibitors