Advanced Nanotechnology in Drug Delivery Systems

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Applied Nano applnano	-	5.9	2020	18.6 Days	CHF 1000	Submit
Applied Sciences applsci	2.9	6.1	2011	15 Days	CHF 2400	Submit
Cancers cancers	4.8	9.0	2009	17.5 Days	CHF 2900	Submit
Molecules molecules	5.1	10.3	1996	15.6 Days	CHF 2700	Submit
Nanomaterials nanomaterials	4.8	10.3	2010	12.5 Days	CHF 2400	Submit
Pharmaceuticals pharmaceuticals	5.7	9.0	2004	14.3 Days	CHF 2900	Submit
Pharmaceutics pharmaceutics	6.9	12.5	2009	16.3 Days	CHF 2900	Submit
Processes processes	3.4	5.7	2013	14.7 Days	CHF 2400	Submit

34 pages, 4467 KB

Open AccessReview

Biomimetic Nanocarriers for Glioblastoma Therapy: Translational Advances and Strategic Challenges

by Bhawana Jain, Sunita Sanwaria, Arti Hadap, I Made Joni, Renny Febrida, Rovina Ruslami, Irwan Purnama, Deoraj Singh and Camellia Panatarani

Cancers 2026, 18(18), 2982; https://doi.org/10.3390/cancers18182982 - 15 Sep 2026

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Abstract

Glioblastoma (GBM) is the most aggressive and common type of brain tumor, characterized by rapid growth and infiltration, as well as high resistance to conventional treatments. Given the persistent challenge posed by the bloodbrain barrier (BBB) to effective drug delivery, a shift in [...] Read more.

Glioblastoma (GBM) is the most aggressive and common type of brain tumor, characterized by rapid growth and infiltration, as well as high resistance to conventional treatments. Given the persistent challenge posed by the bloodbrain barrier (BBB) to effective drug delivery, a shift in therapeutic strategies is required. Biomimetic nanocarriers (BNCs) represent a promising approach for the targeted treatment of malignant brain tumors. By replicating biological structures and functions, BNCs enhance drug stability, facilitate penetration across the BBB, and promote tumor-specific targeting while minimizing the risk of systemic toxicity. These nanocarriers can be engineered using a wide variety of biomaterials, including cell membranes, liposomes, and polymeric systems. Recent preclinical and early clinical studies suggest that BNCs provide a viable method to increase drug bioavailability and therapeutic activity. However, several translational challenges remain, including formulation stability, immunogenicity, regulatory acceptability, and large-scale manufacturing. This review discusses recent advances in BNCs for GBM treatment, drug-targeting strategies, and the structural hurdles that limit their clinical translation. Furthermore, we examine emerging multimodal approaches that integrate BNCs with immunotherapy and gene therapy to enhance personalized GBM treatment. Full article

(This article belongs to the Topic Advanced Nanotechnology in Drug Delivery Systems)

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22 pages, 2532 KB

Open AccessArticle

Optimized Chitosan Nanoparticles for Enhanced Ciprofloxacin Delivery and Activity Against Resistant Bacteria

by Lina Alharbi, Ghaida Abalkhail, Fatimah Alabrah, Faisal Alsuwayyid, Raghad R. Alzahrani, Ibrahim Farh, Majed Halwani, Aiman A. Obaidat and Alaa Eldeen B. Yassin

Pharmaceuticals 2026, 19(9), 1452; https://doi.org/10.3390/ph19091452 - 14 Sep 2026

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Abstract

Background/Objectives: Ciprofloxacin (CIP) is a fluoroquinolone extensively used in hospital settings for the treatment of bacterial infections; however, this antibiotic requires multiple doses because it has poor absorption, rapid elimination, and is ineffective against resistant bacterial strains. Enhanced delivery efficiency could also [...] Read more.

Background/Objectives: Ciprofloxacin (CIP) is a fluoroquinolone extensively used in hospital settings for the treatment of bacterial infections; however, this antibiotic requires multiple doses because it has poor absorption, rapid elimination, and is ineffective against resistant bacterial strains. Enhanced delivery efficiency could also be used in the dose-sparing techniques, resulting in better antibiotic efficacy. The aim of this study was to improve CIP-loaded chitosan nanoparticles (NPs) and to evaluate their capacity to enhance the antibacterial response in sensitive and resistant bacterial isolates. Methods: CIP-loaded chitosan nanoparticles were fabricated via ionic gelation using sodium tripolyphosphate (TPP) as a crosslinking agent. Formulation parameters, such as CIP concentration and polymer-to-crosslinker ratios, were optimized. The obtained nanoparticles were evaluated for particle size, polydispersity index, zeta potential, entrapment efficiency, morphology, stability, and in vitro release studies. Antibacterial efficacy was evaluated by determining minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values against standard and ciprofloxacin-resistant clinical isolates. Results: Successful optimization of these formulations allowed the preparation of stable nanoparticles that ranged from 38.39 to 115.07 nm, highlighting the role of both the formulation composition and polymer-to-crosslinker ratios on the size of the nanoparticles. The formulation exhibits a drug entrapment efficiency of 84.1% and uniform particulate size (38.39 ± 0.63 nm), which were optimized due to the polymer and crosslinker ratios. These nanoparticles showed a slow release of the drug over 220 h, and minimal size instability was noted after 28 days. Encapsulation of CIP resulted in enhanced antibacterial activity, yielding 2–4-fold reductions in MIC and MBC values against methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa resistant strains, compared with free CIP. Conclusions: Optimized CIP-loaded chitosan nanoparticles demonstrated improved antibacterial efficacy against resistant strains and good drug delivery properties. These findings highlight the potential of chitosan-based nanocarrier systems to improve the performance of CIP and antibiotic delivery dose-sparing antibiotic strategies. Full article

(This article belongs to the Topic Advanced Nanotechnology in Drug Delivery Systems)

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39 pages, 24614 KB

Open AccessReview

Pathogenesis-Driven Drug Repurposing with a Self-Nanoemulsifying Delivery System for Parkinson’s Disease

by Kunal Verma, Jaskiran Kaur, Mohit Kumar, Ankit Awasthi, Dinesh Kumar, Neeraj Choudhary and Emad M. Abdallah

Pharmaceuticals 2026, 19(8), 1311; https://doi.org/10.3390/ph19081311 - 20 Aug 2026

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Abstract

Background/Objectives: The aim of the present study was to investigate the mechanisms in Parkinson’s disease (PD), a progressive neurodegenerative disorder characterized by loss of dopaminergic neurons, aggregation of α-synuclein, mitochondrial dysfunction, oxidative stress, neuroinflammation, gut dysbiosis, and blood–brain barrier (BBB) impairment. Although [...] Read more.

Background/Objectives: The aim of the present study was to investigate the mechanisms in Parkinson’s disease (PD), a progressive neurodegenerative disorder characterized by loss of dopaminergic neurons, aggregation of α-synuclein, mitochondrial dysfunction, oxidative stress, neuroinflammation, gut dysbiosis, and blood–brain barrier (BBB) impairment. Although there are several approved therapies that have been developed, their aqueous solubility, oral bioavailability, first-pass metabolism, and inability to penetrate the BBB make them less effective over time. This review is intended to critically analyze the potential of self-nanoemulsifying drug delivery systems (SNEDDSs) as a pathogenesis-related approach to enhance the delivery and therapeutic activity of repurposed drugs and conventional drugs for PD. Methods: A comprehensive literature search was conducted to address the pathogenic mechanisms of PD, the deficiencies of current pharmacotherapy, recent developments in SNEDDS formulation strategies and their application in improving oral bioavailability, lymphatic transport, BBB penetration and targeted brain delivery. A special focus was dedicated to drug repurposing, functionalized SNEDDSs, PEGylation, and gut–brain axis modulation. Results: SNEDDSs significantly enhance the water solubility, stability, intestinal absorption and systemic exposure of poorly water-soluble therapeutic agents and, to a certain extent, lymphatic uptake to avoid first-pass metabolism. These systems include improved brain delivery, decreased pharmacokinetic variability, and prolonged drug levels within the therapeutic range. Moreover, SNEDDSs can be used to deliver multiple molecules that are found to be neuroprotective, antioxidant, anti-inflammatory and probiotic, all at once, which can act on multiple pathogenic mechanisms associated with PD. Functionalized and PEGylated SNEDDSs add further to formulation stability, extend systemic circulation and increase efficiency of brain targeting. Conclusions: SNEDDSs are a promising translational nanomedicine platform for enhancing the effectiveness of conventional and repurposed therapeutics in PD, which address key pharmacokinetic and biological challenges. The next generation of oral therapies with targeted surface engineering, precision drug repurposing and clinical validation will be expected to bring about a faster advancement of drugs that can alter the course of disease rather than giving only symptomatic relief. Full article

(This article belongs to the Topic Advanced Nanotechnology in Drug Delivery Systems)

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38 pages, 7890 KB

Open AccessArticle

Formulation and Optimization of Artemether-Loaded Nanoemulsions by Applying QbD

by Yahya Alhamhoom, Umme Hani, Nagashubha Bobbarjang, Md Abdur Rashid, Bhargav Eranti, Battula Venkatesh, Fahad AlQahtani, Helal A. Helal, Mahesh Vaggu and Maccha Kiran Sai

Pharmaceuticals 2026, 19(8), 1264; https://doi.org/10.3390/ph19081264 - 11 Aug 2026

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Abstract

Background: Nanoemulsions are colloidal drug delivery systems consisting of an oil phase dispersed in water and stabilized by surfactants, producing droplets in the nanometer range. By virtue of their small droplet size and large interfacial area, they enhance drug dissolution, intestinal absorption, [...] Read more.

Background: Nanoemulsions are colloidal drug delivery systems consisting of an oil phase dispersed in water and stabilized by surfactants, producing droplets in the nanometer range. By virtue of their small droplet size and large interfacial area, they enhance drug dissolution, intestinal absorption, and site-specific delivery while offering controlled, prolonged release and a reduced risk of systemic side effects. Artemether (ART), an antimalarial agent, suffers from poor aqueous solubility and limited oral bioavailability, which restricts its therapeutic efficacy. Objective: The present study aimed to develop and optimize an Artemether-loaded nanoemulsion to improve the drug’s dissolution rate and oral bioavailability. Methods: The nanoemulsion was formulated using a combination of Sunflower oil and Vippa oil as the oil phase, with Tween 80 and Span 80 as the surfactant system, and was prepared by an ultrasonication technique. A three-factor, three-level Box–Behnken Design (BBD) was employed to systematically optimize the formulation composition and processing parameters. The formulations were evaluated for droplet size, polydispersity index (PDI), zeta potential, drug content, entrapment efficiency, pH, viscosity, refractive index, electrical conductivity, and cumulative in vitro drug release. Results: The optimized nanoemulsion exhibited a droplet size of 139.6 ± 1.3 nm, a PDI of 0.256 ± 0.03 indicating a narrow and uniform size distribution, and a zeta potential of −30.08 ± 1.1 mV reflecting good physical stability. The formulation demonstrated a high entrapment efficiency of 95.42 ± 1.18%, confirming efficient drug loading within the lipid core. Additional physicochemical evaluation revealed a pH of 6.4 ± 0.2, a low viscosity of 2.84 ± 0.15 cP, a refractive index of 1.338 ± 0.002, and a conductivity of 215 ± 12 µS/cm, collectively confirming the formation of a physiologically compatible, isotropic oil-in-water nanoemulsion. The formulation achieved 97.90 ± 0.97% cumulative in vitro drug release over a 12 h period, demonstrating a sustained release profile. Conclusions: The optimized Artemether-loaded nanoemulsion, developed using a Box–Behnken Design, significantly enhanced the drug’s dissolution and exhibited favorable physicochemical characteristics, high entrapment efficiency, and controlled release behavior. These findings suggest that nanoemulsion is a promising carrier system warranting further in vivo evaluation to confirm its potential for improving the oral bioavailability of Artemether. Full article

(This article belongs to the Topic Advanced Nanotechnology in Drug Delivery Systems)

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16 pages, 1305 KB

Open AccessArticle

Enhanced Transdermal Delivery of rhHAPLN1 by Soluball^® Promotes Pericellular Matrix Stability and Keratinocyte Protection

by Kyeong Hyeon Lee, Kang Min Kim, Ju Hyuk Han, Kyung Taek Oh and Dae Kyong Kim

Pharmaceutics 2026, 18(8), 947; https://doi.org/10.3390/pharmaceutics18080947 - 31 Jul 2026

Viewed by 461

Abstract

Background/Objectives: The pericellular matrix (PCM), a highly hydrated hyaluronan (HA)-rich extracellular structure surrounding keratinocytes, serves as a critical regulator of cellular protection, mechanobiological signaling, and epidermal microenvironmental homeostasis. Increasing evidence suggests that age- and stress-associated degradation of the HA-rich PCM contributes to impaired [...] Read more.

Background/Objectives: The pericellular matrix (PCM), a highly hydrated hyaluronan (HA)-rich extracellular structure surrounding keratinocytes, serves as a critical regulator of cellular protection, mechanobiological signaling, and epidermal microenvironmental homeostasis. Increasing evidence suggests that age- and stress-associated degradation of the HA-rich PCM contributes to impaired regenerative capacity and increased cellular vulnerability. Recombinant human hyaluronan and proteoglycan link protein 1 (rhHAPLN1) has emerged as a promising PCM-stabilizing biomolecule; however, its therapeutic application remains limited by poor skin permeability resulting from the barrier properties of the stratum corneum and the molecular size constraints governing hydrophilic macromolecule delivery. Methods: In the present study, we developed Soluball^®, a dodecylamine-templated mesoporous silica-based carrier system designed to enhance the transdermal delivery of rhHAPLN1. Results: In vitro analyses demonstrated that rhHAPLN1 effectively preserved both the structural integrity and functional hydrodynamic volume of the PCM against hyaluronidase (HAdase)-induced degradation in HaCaT keratinocytes. Furthermore, rhHAPLN1 exhibited no significant cytotoxicity at concentrations up to 1 μg/mL and significantly enhanced keratinocyte proliferation under serum-free conditions. Physicochemical characterization revealed that Soluball^® possessed a relatively uniform particle size distribution (284.6 nm), a high specific surface area (1048 m²/g), and a mesoporous architecture with an average pore diameter of 3.8 nm, supporting efficient loading of hydrophilic biomolecules. Ex vivo permeation studies using human cadaver skin demonstrated that Soluball^®-encapsulated rhHAPLN1 (H-S powder) significantly enhanced cumulative transdermal permeation compared with free rhHAPLN1 (5.54% vs. 0.88%, respectively). To further evaluate platform versatility, water-soluble Vitamin C was employed as a secondary model cargo. Vita-Soluball^® exhibited markedly enhanced permeation across both Strat-M^® artificial membranes and pig epidermis, achieving cumulative permeation values of 119.12 ± 9.38 μg/mL and 150.39 ± 29.20 μg/mL, respectively. Conclusions: Collectively, these findings suggest that rhHAPLN1 functions as an effective stabilizer of the HA-rich PCM and that Soluball^® enhances the transdermal delivery of hydrophilic biomolecules. Overall, Soluball^® may represent a promising transdermal delivery platform for hydrophilic biomolecules, although further in vivo validation is warranted. Full article

(This article belongs to the Topic Advanced Nanotechnology in Drug Delivery Systems)

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22 pages, 4935 KB

Open AccessArticle

Liver-Directed Cyp2e1 RNA Interference Attenuates Hepatotoxicity Induced by Triptolide, a Bioactive Diterpenoid from Tripterygium wilfordii Hook. f.

by Zijin Zhang, Wenzhao Jiang, Ruoyao Sang, Zhen Ouyang, Qian Wu and Yuan Wei

Pharmaceuticals 2026, 19(7), 1087; https://doi.org/10.3390/ph19071087 - 15 Jul 2026

Viewed by 399

Abstract

Objectives: Triptolide (TP), a bioactive diterpenoid from Tripterygium wilfordii Hook. f., has pharmacological activity, but repeated exposure is limited by hepatotoxicity. CYP2E1 is a hepatic metabolic-redox enzyme linked to oxidative liver injury. This study evaluated whether liver-directed Cyp2e1 RNA interference mitigates TP-induced subacute [...] Read more.

Objectives: Triptolide (TP), a bioactive diterpenoid from Tripterygium wilfordii Hook. f., has pharmacological activity, but repeated exposure is limited by hepatotoxicity. CYP2E1 is a hepatic metabolic-redox enzyme linked to oxidative liver injury. This study evaluated whether liver-directed Cyp2e1 RNA interference mitigates TP-induced subacute hepatotoxicity without evidence of a marked reduction in short-term systemic TP exposure. Methods: Cyp2e1-targeting siRNA was encapsulated in lipid nanoparticles (si-Cyp2e1 LNPs) and validated for hepatic CYP2E1 protein knockdown in female C57BL/6J mice. Subacute liver injury was induced by oral TP at 800 μg/kg/day for 7 days. Prophylactic and concurrent si-Cyp2e1 regimens were evaluated using serum transaminases, gross liver morphology, H&E histopathology with blinded semi-quantitative scoring, oxidative-stress indices, RNA-seq, RT-qPCR, Western blotting, and exploratory LC-MS/MS pharmacokinetic analysis. Results: si-Cyp2e1 LNPs showed favorable nanoscale properties and robust hepatic CYP2E1 protein knockdown. Both regimens reduced ALT/AST elevations, improved gross liver appearance and histological injury scores, decreased hepatic ROS and malondialdehyde, and restored glutathione and superoxide dismutase. Transcriptomic and molecular analyses indicated TP-associated PI3K/AKT activation and reduced PI3K/AKT phosphorylation after si-Cyp2e1 treatment. Exploratory pharmacokinetic profiling showed a lower early plasma TP peak, whereas AUC0–t and AUC0–∞ appeared broadly comparable within the 0–3 h observation window. Conclusions: Liver-directed Cyp2e1 silencing provided proof-of-concept hepatoprotection against repeated TP exposure, accompanied by redox recovery and attenuated stress-associated PI3K/AKT activation. Because CYP2E1 enzymatic activity, TP-derived reactive metabolites, and pathway causality were not directly tested, these findings should be interpreted as pathway-associated evidence requiring further validation. Full article

(This article belongs to the Topic Advanced Nanotechnology in Drug Delivery Systems)

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27 pages, 12892 KB

Open AccessArticle

Study on Synergistic Treatment of Pancreatic Cancer by Multiple Small Interfering Ribonucleic Acid Lipid Nanoparticles of Disk Domain Receptor 1, Transforming Growth Factor β1, Tumor-Associated Calcium Signal Transduction Protein 2, and Polyligand Proteoglycan 1

by Rongrong Wang, Yiying Zeng, Zhaowu Zeng and Tian Xie

Pharmaceutics 2026, 18(7), 775; https://doi.org/10.3390/pharmaceutics18070775 - 25 Jun 2026

Viewed by 697

Abstract

Background/Objective: This study aimed to use multiple disk domain receptor 1 (DDR1), transforming growth factor β1 (TGFβ-1), tumor-associated calcium signal transduction protein 2 (TACSTD2), and polyligand proteoglycan 1 (SDC1) siRNA to treat pancreatic cancer with the goals of high specificity, significant therapeutic [...] Read more.

Background/Objective: This study aimed to use multiple disk domain receptor 1 (DDR1), transforming growth factor β1 (TGFβ-1), tumor-associated calcium signal transduction protein 2 (TACSTD2), and polyligand proteoglycan 1 (SDC1) siRNA to treat pancreatic cancer with the goals of high specificity, significant therapeutic efficacy, and relatively low toxicity. Methods: (1) A microfluidic method was used to prepare siRNA-LNPs with different formulations. (2) Quantitative PCR (qPCR) and Western blot assays were used to detect the inhibitory effect of different-prescription siRNA-LNP formulations on mRNA and protein expression levels of related genes in PaTu 8988 pancreatic cells. (3) The anti-pancreatic cancer effect of multiple siRNAs combined with LNPs in vivo was evaluated using the BALB/c nude mouse model with subcutaneous pancreatic cancer xenografts. Results: (1) Three siRNA-LNP formulations, DMG, CE 1.5, and CE 0.75, were successfully prepared, exhibiting small particle sizes and uniform distribution. (2) qPCR and Western blot results indicated that DDR1, TGFβ-1, TACSTD2, and SDC1 siRNA-LNP significantly inhibited related genes’ mRNA and protein expression in pancreatic cancer PaTu 8988 cells. (3) Efficacy studies in animals indicated that multiple siRNA combined with LNPs in each group exhibited significant antitumor effects on pancreatic cancer tumor-bearing nude mice. The therapeutic efficacy of the combined siRNAs was superior to that of single siRNA treatments, indicating a clear combined effect, especially with three- and four-siRNA combinations. Conclusions: The prepared DDR1/TGFβ-1/TACSTD2/SDC1 siRNA-loaded LNP demonstrated a small particle size, high gene inhibition efficiency, and a significant therapeutic effect in treating pancreatic cancer. Its safety is generally acceptable, but attention should be paid to the toxicity caused by LNP excipients, especially cationic lipids. Full article

(This article belongs to the Topic Advanced Nanotechnology in Drug Delivery Systems)

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20 pages, 6249 KB

Open AccessArticle

Sildenafil-Coated Silver Nanoparticles for Anal Fissure Wound Healing—A Combined Experimental/Molecular Docking Study

by Mahboubeh Dolatyari, Parisa Rostami, Mahsa Hejazad, Ali Rostami, Manouchehr Khoshbaten, Mahdi Dolatyari, Hamit Mirtagioglu and Axel Klein

Appl. Nano 2026, 7(2), 17; https://doi.org/10.3390/applnano7020017 - 19 Jun 2026

Viewed by 1209

Abstract

PVP-stabilized silver nanoparticles (Ag NPs) were functionalized with sildenafil (Sil), leading to spherical NPs (Ag@Sil NPs) with a size of about 30 nm as observed through transmission electron microscopy and dynamic light scattering. Fourier-transformed IR spectroscopy confirmed the covering of the particles with [...] Read more.

PVP-stabilized silver nanoparticles (Ag NPs) were functionalized with sildenafil (Sil), leading to spherical NPs (Ag@Sil NPs) with a size of about 30 nm as observed through transmission electron microscopy and dynamic light scattering. Fourier-transformed IR spectroscopy confirmed the covering of the particles with Sil. The Ag@Sil NPs were incorporated into a 0.1 wt% ointment and tested for the treatment of acute anal fissures in a preliminary medical study involving 50 patients. Typical symptoms such as pain, bleeding, itching, and mass sensation were improved in the intervention group with no adverse effects. Molecular docking showed strong interactions with docking scores slightly above −10 kcal/mol between sildenafil and two different model complexes [Ag–Sil]⁺ for the Ag-bound sildenafil with either piperazine-N- or pyrazole-N-bound Ag⁺ ions and the muscarinic M2 and the nicotinic acetylcholine α3β4 receptor, which are both involved in anal sphincter regulation. All three showed superior binding compared with nitroglycerin and L-arginine. The residue analysis revealed a higher number of relevant interactions for the sildenafil and the two Ag⁺ complexes, compared to nitroglycerin and L-arginine, fully in line with the differences in the docking scores. Full article

(This article belongs to the Topic Advanced Nanotechnology in Drug Delivery Systems)

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25 pages, 2316 KB

Open AccessArticle

Engineering Selenium–Chitosan Nanoparticles for Enhanced Hepatic Delivery of Sunitinib and Improved In Vitro Anticancer Activity in Hepatocellular Carcinoma Models

by Ahmed S.G. Srag El-Din, Eman Hamza, Ahmed Y. Kira, Sameh Saber, Mona H. Zohny, Ohoud Y. Alshehri, Reham A. Al-Dhelaan, Eslam Osama Mohamed and Heba I. Elagamy

Pharmaceuticals 2026, 19(6), 898; https://doi.org/10.3390/ph19060898 - 5 Jun 2026

Cited by 1 | Viewed by 587

Abstract

Background/Objectives: Hepatocellular carcinoma (HCC) remains difficult to treat because systemic therapy is constrained by limited selectivity, resistance, and toxicity. This study aimed to engineer selenium–chitosan nanoparticles loaded with sunitinib (SeNPs-Ch-SUN) to enhance hepatic delivery and improve anticancer activity against HCC. Methods: [...] Read more.

Background/Objectives: Hepatocellular carcinoma (HCC) remains difficult to treat because systemic therapy is constrained by limited selectivity, resistance, and toxicity. This study aimed to engineer selenium–chitosan nanoparticles loaded with sunitinib (SeNPs-Ch-SUN) to enhance hepatic delivery and improve anticancer activity against HCC. Methods: The developed system was characterized for particle size (PS), zeta potential (ZP), loading efficiency (LE%), in vitro release, and storage stability. Their cytotoxicity was evaluated in parental HepG2 and Huh-7 cells, multidrug-resistant HepG2 cells, SUN-resistant Huh-7 cells, and THLE-2 normal hepatocytes. In vivo hepatic distribution after intravenous administration was also assessed in rats. Results: SeNPs-Ch-SUN exhibited a mean PS of 93.62 ± 1.06 nm, positive ZP of +24.47 ± 1.31 mV, and LE of 83.8 ± 2.16%. FTIR supported drug association with the chitosan-stabilized selenium system. Compared with free sunitinib, SeNPs-Ch-SUN exhibited sustained drug release, with 51.17 ± 1.26% released at 24 h, whereas the free drug was almost completely released within 3 h. This controlled-release behavior translated in vivo into prolonged hepatic retention and superior liver exposure after intravenous administration. SeNPs-Ch-SUN significantly increased liver AUC_0–24 to 77.23 ± 10.56 µg/g·h, compared with 36.39 ± 9.66 µg/g·h for free SUN, corresponding to an approximately 2.1-fold increase in hepatic exposure. SeNPs-Ch-SUN enhanced cytotoxicity in parental and resistant HCC models, lowered IC₅₀ values, improved selectivity toward malignant cells, and reduced resistance index (RI) in MDR-HepG2 cells, while maintaining reduced toxicity toward normal hepatocytes relative to the free SUN. Conclusions: SeNPs-Ch-SUN represents a promising liver-directed nanoplatform for sunitinib delivery. Full article

(This article belongs to the Topic Advanced Nanotechnology in Drug Delivery Systems)

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28 pages, 5370 KB

Open AccessArticle

Enhancing Antibacterial Activity of Medinilla speciosa Blume Fruits Against Cutibacterium acnes Through Phytosome Delivery: An In Vivo Study

by Ririn Puspadewi, Tiana Milanda, Muhaimin Muhaimin, Anis Yohana Chaerunisaa, Sri Agung Fitri Kusuma, Yuni Elsa Hadisaputri, Faizal Hermanto and Lia Mardiana

Pharmaceuticals 2026, 19(6), 825; https://doi.org/10.3390/ph19060825 - 25 May 2026

Cited by 1 | Viewed by 676

Abstract

Background/Objectives: The fruit of Medinilla speciosa Blume fruit contains flavonoids with potent activity against Cutibacterium acnes, but their clinical application is hindered by poor bioavailability. This study aimed to develop, characterize, and evaluate a phytosome-based vesicular system to enhance the in [...] Read more.

Background/Objectives: The fruit of Medinilla speciosa Blume fruit contains flavonoids with potent activity against Cutibacterium acnes, but their clinical application is hindered by poor bioavailability. This study aimed to develop, characterize, and evaluate a phytosome-based vesicular system to enhance the in vivo antibacterial efficacy of the fruit’s ethyl acetate fraction (EAFMS). Methods: Phytosomes were synthesized via antisolvent precipitation using a 1:3 EAFMS-to-phospholipid ratio. Formulations were characterized for particle size, polydispersity index (PDI), zeta potential, entrapment efficiency (EE), and in vitro release. Antibacterial efficacy was assessed in C. acnes-induced Wistar rats over three days. Results: EAFMS showed superior antibacterial activity with a 93.5% relative potency compared to tetracycline. The optimized phytosomes exhibited favorable physicochemical properties: particle size of phytosome 244.60 ± 0.85 nm, PDI of phytosome 0.396 ± 0.08, zeta potensial of phytosome −56.70 ± 2.08 mV, and EE of phytosome 89.46 ± 0.45%. The formulation achieved a 76.504% cumulative release at 8 h. In vivo trials demonstrated that the phytosome cream significantly reduced bacterial colony counts and diminished inflammatory cell infiltration compared to the cream base. Conclusions: The phytosome system effectively improves the stability and delivery of M. speciosa flavonoids, significantly enhancing their antibacterial and anti-inflammatory performance against acne. Full article

(This article belongs to the Topic Advanced Nanotechnology in Drug Delivery Systems)

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20 pages, 2141 KB

Open AccessArticle

Formulation of Metformin-Loaded Chitosan Nanoparticles and In Vivo Evaluation of Its Hypoglycemic Effects

by Zainab Omeed Awchee, Airemwen Collins Ovenseri, Ahmad Saleh Malkawi and Leyla Beba Pozharani

Molecules 2026, 31(9), 1539; https://doi.org/10.3390/molecules31091539 - 6 May 2026

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Abstract

This study formulated and characterized metformin-loaded chitosan nanoparticles (NPs) using the ionic gelation technique and evaluated the drug release kinetics. Characterization confirmed successful drug encapsulation, with Fourier-transform infrared spectroscopy (FTIR) indicating compatibility, and X-ray diffraction (XRD) showing attenuation of characteristic metformin reflections consistent [...] Read more.

This study formulated and characterized metformin-loaded chitosan nanoparticles (NPs) using the ionic gelation technique and evaluated the drug release kinetics. Characterization confirmed successful drug encapsulation, with Fourier-transform infrared spectroscopy (FTIR) indicating compatibility, and X-ray diffraction (XRD) showing attenuation of characteristic metformin reflections consistent with reduced crystalline contribution after encapsulation. Particle sizes ranged from 74.28 to 86.82 nm. The NPs exhibited stable zeta potentials (+42.38 to +49.06 mV) and high entrapment efficiencies (68.42–81.26%). In vitro drug release studies at pH 7.4 and pH 2.0 demonstrated an initial burst release, followed by sustained release over 24 h. The cumulative drug release ranged from 81.92% to 97.72% at pH 7.4 and 89.4% to 98.1% at pH 2.0, with a faster release at pH 2.0. Drug release kinetics followed first-order for batch MN1, while batches MN2 and MN3 best fitted into the Higuchi model, indicating diffusion-controlled release through the chitosan polymeric network. The formulated metformin nanoparticles demonstrated significant potent dose-related and time-dependent cytotoxic effect against ovarian cancer cell lines and in vivo blood glucose lowering effect compared to the conventional dosage forms and control (p < 0.05). These findings highlight the potential of metformin-loaded chitosan NPs for sustained drug delivery, which may enhance patient compliance by reducing dosing frequency. Future studies should further explore their clinical applications. Full article

(This article belongs to the Topic Advanced Nanotechnology in Drug Delivery Systems)

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14 pages, 3563 KB

Open AccessArticle

Co-Delivery of Glucose Oxidase and Iron-Doped ZIF-8 as a pH-Responsive Ferroptosis and Starvation Agent for Triple-Negative Breast Cancer Therapy

by Zhibin Lin, Yuanxin Zhao, Lin Tang and Jianhua He

Nanomaterials 2026, 16(9), 533; https://doi.org/10.3390/nano16090533 - 28 Apr 2026

Viewed by 1006

Abstract

Currently, single-modal tumor therapy has significant limitations, while multi-modal combination therapy can overcome this bottleneck and open up new pathways for enhancing the efficacy of tumor therapy. However, it is still difficult to design a functionalized nanocarrier that can simultaneously mediate multiple therapeutic [...] Read more.

Currently, single-modal tumor therapy has significant limitations, while multi-modal combination therapy can overcome this bottleneck and open up new pathways for enhancing the efficacy of tumor therapy. However, it is still difficult to design a functionalized nanocarrier that can simultaneously mediate multiple therapeutic approaches. To tackle this challenge, we developed a multifunctional nano-codelivery system with glucose oxidase (GOx) loaded inside iron-doped zeolitic imidazolate framework-8 (Fe/ZIF-8), abbreviated as GFZ. This system effectively integrates the synergy and complementarity between ferroptosis therapy and starvation therapy (STT). Herein, GFZ innovatively combines the pH sensitivity of the ZIF-8 skeleton with the EPR effect of nanoparticles to achieve on-demand triggered release, significantly improving the accuracy of tumor targeting. Furthermore, GOx-mediated STT effectively alleviates the insufficiency of endogenous H₂O₂ during the ferroptosis process, thereby enhancing and synergizing with ferroptosis therapy. Experiments demonstrated both in vitro and in vivo that GFZ activates antitumor cascade reactions, inhibits tumor recurrence and metastasis, and exhibits excellent biocompatibility. Consequently, given its remarkable potential, GFZ is poised to emerge as a new mode of nano-delivery platform. Full article

(This article belongs to the Topic Advanced Nanotechnology in Drug Delivery Systems)

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25 pages, 1489 KB

Open AccessReview

Nanoparticles: An Emerging Hope in Cancer Therapy

by Shahid Sher, Rosny Jean and Zaman Khan

Nanomaterials 2026, 16(9), 515; https://doi.org/10.3390/nano16090515 - 24 Apr 2026

Cited by 1 | Viewed by 1575

Abstract

Cancer remains a major global health challenge, characterized by abnormal cell growth and metastasis. Current limitations of conventional therapies, particularly non-specific toxicity harming healthy cells, highlight the need for more targeted approaches. Nanotechnology offers a revolutionary solution, utilizing nanoparticles (NPs) for precise drug [...] Read more.

Cancer remains a major global health challenge, characterized by abnormal cell growth and metastasis. Current limitations of conventional therapies, particularly non-specific toxicity harming healthy cells, highlight the need for more targeted approaches. Nanotechnology offers a revolutionary solution, utilizing nanoparticles (NPs) for precise drug delivery to tumor sites while minimizing off-target effects. These nanometer-scale particles enable superior binding to cancer cell membranes, the tumor microenvironment, or nuclear receptors, facilitating significantly higher local concentrations of therapeutic agents. NPs, synthesized via physical, chemical, or biological methods, are categorized as organic (organic material-based) or inorganic (metallic particle-based). Key delivery mechanisms include the Enhanced Permeability and Retention (EPR) effect and Active Transport and Retention (ATR). This review specifically examines NP applications for the most prevalent cancers in the US (2025): breast, prostate, and lung. Gold and magnetic NPs show significant promise for early breast cancer detection. For lung cancer, polymeric NPs like PCL, PLA, and PLGA are effective carriers for peptides, proteins, and nucleic acids. BIND-014, a docetaxel-loaded NP formulation, represents an emerging strategy for prostate cancer. Clinically established examples include liposomal doxorubicin and albumin-bound paclitaxel. We comprehensively discuss the synthesis methods, delivery mechanisms, and the current landscape of NPs in research and clinical trials for these cancers. This analysis underscores the potential of nanotechnology to provide more effective and targeted therapeutic options for cancer patients in the future. A distinctive feature of this review is its comparative cancer-specific analysis of NP platforms in breast, prostate, and lung cancers. Unlike previous generalized reviews, this work integrates synthesis strategies, delivery mechanisms, translational challenges, and clinically relevant formulations to provide a bench-to-bedside perspective on the future of nanomedicine in oncology. Full article

(This article belongs to the Topic Advanced Nanotechnology in Drug Delivery Systems)

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22 pages, 2527 KB

Open AccessArticle

A Degradable Nanosystem Based on Small Gold Nanoparticles and Albumin for Amyloid Aggregation Inhibition

by Matías Levio, Francisco Rossel Carrera, Fredys Sánchez Hoyos, Maycol Huerta, Carlos Alamos, Rodrigo Vásquez-Contreras, Marcelo J. Kogan and Eyleen Araya Fuentes

Pharmaceutics 2026, 18(4), 504; https://doi.org/10.3390/pharmaceutics18040504 - 19 Apr 2026

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Abstract

Background/Objectives: Beta amyloid (Aβ) aggregates play a central role in the pathophysiology of Alzheimer’s disease (AD), and their detection and modulation remain major challenges in developing effective therapeutic and diagnostic strategies. Previously, gold nanoparticles with plasmonic and optical properties in the near-infrared [...] Read more.

Background/Objectives: Beta amyloid (Aβ) aggregates play a central role in the pathophysiology of Alzheimer’s disease (AD), and their detection and modulation remain major challenges in developing effective therapeutic and diagnostic strategies. Previously, gold nanoparticles with plasmonic and optical properties in the near-infrared (NIR) region and photothermal capabilities have been designed for detecting and disaggregating Aβ aggregates. However, these systems often face limitations related to biodegradability, long-term accumulation, and safety. In this work, a degradable NIR-responsive nanosystem based on small gold nanoparticles (sAuNPs), potentially excretable due to their small size, encapsulated within bovine serum albumin (BSA) and functionalized with the all-D peptide D3, was developed to inhibit Aβ aggregation. Methods: sAuNPs (~5–6 nm), functionalized with HS-PEG-NH₂, were encapsulated into BSA nanoparticles using a desolvation method and subsequently conjugated to D3, resulting in the nanosystem f-sAuNPs-BSANPs-D3. The nanosystem was characterized by UV–Vis–NIR spectroscopy, dynamic light scattering, zeta potential analysis, electron microscopy, and nanoparticle tracking analysis. The effects of the nanosystem on Aβ_1–42 aggregation were evaluated using a thioflavin T assay and electron microscopy. Additionally, the effects of f-sAuNPs-BSANPs-D3 on cell viability and its stability against trypsin digestion were assessed. Results: The nanosystem exhibited a measurable photothermal response under NIR irradiation and significantly reduced fibril formation. It did not affect the viability of SH-SY5Y neuronal cells at the tested concentrations. Trypsin incubation experiments demonstrated that the nanosystem remained stable at low enzyme concentrations mimicking plasma conditions, whereas higher enzyme concentrations induced degradation of the albumin matrix and subsequent disaggregation of sAuNPs. Conclusions: Overall, this study presents a degradable, albumin-based sAuNP nanosystem with NIR-responsive properties and potential for nanomedicine applications to inhibit Aβ aggregation in AD. Full article

(This article belongs to the Topic Advanced Nanotechnology in Drug Delivery Systems)

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26 pages, 3445 KB

Open AccessArticle

Effect of Microfluidization Technique on the Physicochemical Characteristics of Cannabidiol Nanoemulsions

by Andrés Fernando Sánchez Martínez, Luis Eduardo Diaz Barrera, Natalia Elizabeth Conde Martínez, Rosa Helena Bustos Cruz, Martha Ximena León Delgado and María Ximena Quintanilla Carvajal

Nanomaterials 2026, 16(8), 459; https://doi.org/10.3390/nano16080459 - 14 Apr 2026

Viewed by 947

Abstract

This study examines the effect of microfluidization on the physicochemical properties, stability, release behavior, and cytocompatibility of cannabidiol (CBD) nanoemulsions intended for topical application. CBD is a non-psychoactive cannabinoid characterized by anti-inflammatory and analgesic activity; however, its therapeutic use is limited by low [...] Read more.

This study examines the effect of microfluidization on the physicochemical properties, stability, release behavior, and cytocompatibility of cannabidiol (CBD) nanoemulsions intended for topical application. CBD is a non-psychoactive cannabinoid characterized by anti-inflammatory and analgesic activity; however, its therapeutic use is limited by low solubility and poor bioavailability. To address these limitations, nanoemulsions were formulated using avocado oil and Tween 80 and optimized through a Box–Behnken experimental design evaluating microfluidization pressure (5000–20,000 PSI), CBD concentration (0–2%), and oil content (8–10%). Nanoemulsions were characterized over a 60-day period in terms of droplet size, dispersity index (D), and zeta potential. An increase in processing pressure led to a reduction in both droplet size and dispersity, with optimal conditions identified between 11,000 and 15,000 PSI. Higher oil and CBD concentrations were associated with an increase in the magnitude of the zeta potential, contributing to electrostatic stabilization of the system. Encapsulation efficiency reached approximately 81.4%. Cell viability assays in HaCaT keratinocytes indicated no significant cytotoxic effects. The optimized formulation exhibited a sigmoidal CBD release profile best described by Weibull and Gompertz models (R² ≈ 0.99), suggesting combined diffusion and interfacial mechanisms that support efficient topical delivery. Full article

(This article belongs to the Topic Advanced Nanotechnology in Drug Delivery Systems)

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32 pages, 16205 KB

Open AccessArticle

pH-Responsive Nanostructured Calcium Phosphate Microrods as Pulmonary Delivery Platform: Fabrication, Characterization, and Comparative Assessment of Cytotoxic and Transcriptomic Responses in Alveolar Macrophages

by Jannis Fries, Richard Bachmann, Amalia Schechtel, Oliver Janka, Julia Schulze-Hentrich and Marc Schneider

Pharmaceutics 2026, 18(4), 428; https://doi.org/10.3390/pharmaceutics18040428 - 31 Mar 2026

Viewed by 1703

Abstract

Background: Nanostructured, rod-shaped microparticles represent a promising drug delivery platform for the pulmonary delivery and targeting of alveolar macrophages by exploiting the aerodynamic advantages of fiber-like geometries. These microrods feature a hierarchical architecture, designed for potential macromolecular payloads, and silica (SiO₂)-based [...] Read more.

Background: Nanostructured, rod-shaped microparticles represent a promising drug delivery platform for the pulmonary delivery and targeting of alveolar macrophages by exploiting the aerodynamic advantages of fiber-like geometries. These microrods feature a hierarchical architecture, designed for potential macromolecular payloads, and silica (SiO₂)-based systems have previously been shown to successfully deliver oligonucleotides in vitro. However, current microrod systems mainly rely on nanoparticulate SiO₂-based frameworks with limited biodegradability and lack a specific escape mechanism to the cytosol. Therefore, a nanostructured calcium phosphate (CaP) framework is proposed as a biodegradable and resorbable alternative, featuring pH-responsive dissolution under endolysosomal conditions. Methods and Results: This study presents the fabrication of nanostructured, rod-shaped calcium phosphate microparticles and discusses their suitability as a potential pulmonary drug delivery platform. The particles feature dissolution-driven disintegration in acidic and ion-rich environments relevant to phagolysosomes. In addition, the particles exhibited a favorable acute cytotoxicity profile in the murine alveolar macrophage cell line MH-S compared with their SiO₂-based counterparts. Comparative RNA-seq analysis of MH-S exposed to the particles indicates a mild transcriptomic response, while canonical signatures of classical or alternative macrophage activation programs were not observed, supporting a generally well-tolerated exposure profile of the carrier. Conclusions: Together, these findings establish key prerequisites for employing calcium phosphate microrods as a biodegradable pulmonary carrier platform in subsequent studies incorporating therapeutic cargos. Full article

(This article belongs to the Topic Advanced Nanotechnology in Drug Delivery Systems)

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