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The Development of Drug Delivery Systems and Pharmaceutical Formulations for the Treatment of Infectious Diseases

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

Deadline for manuscript submissions: closed (31 July 2026) | Viewed by 10540

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Dr. José María Bermúdez

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Instituto de Investigaciones para la Industria Química, Universidad Nacional de Salta—Consejo Nacional de Investigaciones Científicas y Técnicas, Av. Bolivia 5150, Salta 4400, Argentina
Interests: drug delivery systems; modified drug release; neglected infectious diseases; mathematical modeling

Prof. Dr. Santiago Daniel Palma

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1. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica, Consejo Nacional de Investigaciones Científicas y Tecnológicas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Av. Haya de la Torre y Medina Allende, Córdoba 5000, Argentina
2. Pill.AR Apotheke Revolution S.A, Córdoba 5000, Argentina
Interests: materials chemistry; nanotechnology; nanoparticles; vaccines; nanomaterials; gels; surfactants; solid dispersion; formulations; rheology
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Special Issue Information

Dear Colleagues,

This Special Issue focuses on the development of innovative drug delivery systems (DDSs) and pharmaceutical formulations to optimize the treatment of infectious diseases, with an emphasis on bacterial, viral, and parasitic infections. It highlights advanced DDS technologies, including polymer-based systems, nanocarriers, and emerging platforms, aimed at enhancing therapeutic efficacy, stability, and targeted drug delivery. Particular attention is given to the application of polymers in formulations designed for controlled, sustained, or targeted release, addressing challenges posed by multidrug-resistant pathogens and difficult-to-treat infections. This Special Issue also explores cutting-edge advances in nanoformulations, liposomal carriers, and biocompatible materials that improve drug penetration, reduce toxicity, and enable site-specific delivery. By bringing together the latest research, this Special Issue underscores the potential of these technologies to tackle the growing challenges of infectious diseases, enhance clinical outcomes, and combat emerging threats, including parasitic infections.

Dr. José María Bermúdez
Prof. Dr. Santiago Daniel Palma
Guest Editors

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Keywords

drug delivery systems
pharmaceutical formulations
nanoformulations
parasitic infections
controlled drug release

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Published Papers (6 papers)

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Research

12 pages, 221 KB

Open AccessFeature PaperArticle

Effect of Combined Polyphenol on the Disease Course in Children Diagnosed with Influenza

by Eren Güzeloğlu, Vefik Arica, Belen Ateş, Taner Adigüzel, Aysun Boğa, Ali Rıza Akgün, Mehmet Tolga Köle, Ayşe Ademoğlu, Hatice Demet Kemalbay, Feyza Aydın Özgür, Hatice Yıldız Özkan, Eda Çiftçi and Hüseyin Dağ

Pharmaceutics 2026, 18(7), 858; https://doi.org/10.3390/pharmaceutics18070858 - 14 Jul 2026

Viewed by 372

Abstract

Objective: This multicenter retrospective real-world data study aimed to evaluate whether the use of a preparation containing polyphenol, vitamin D3, vitamin C, and zinc in addition to antiviral therapy was associated with symptom duration and severity, time to fever resolution, and functional recovery in children diagnosed with influenza. Materials and Methods: This was a five-center, multicenter, retrospective, comparative real-world data analysis. A total of 128 patients aged 4–10 years with a clinical diagnosis of influenza were classified into a control group receiving antiviral therapy alone (n = 64) and a combined polyphenol group receiving, in addition to antiviral therapy, a preparation containing polyphenol, vitamin D3, vitamin C, and zinc (n = 64). Clinical data were obtained from electronic patient records and parent-reported information. Symptom severity (0–3 ordinal score), recovery time, and functional outcomes were assessed on Days 0, 3, 5, and 7. Continuous variables were compared using the independent-samples t test, categorical variables using the chi-square or Fisher exact test, and changes over time using a repeated-measures general linear model. Statistical significance was accepted as a two-sided p value of <0.05. Results: In this study including 128 pediatric patients, there were no significant differences between the combined polyphenol and control groups in demographic or baseline clinical characteristics (p > 0.05). During follow-up, all symptom scores improved more rapidly and markedly in the combined polyphenol group than in the control group. By Day 3, significant differences were observed between groups in fever, cough, rhinorrhea, sore throat, fatigue, general condition, and physical activity scores (p < 0.001 for all parameters). By Day 5, almost complete resolution of symptoms (score 0) was observed in the combined polyphenol group, whereas symptoms persisted to a substantial extent in the control group (p < 0.001). The time to fever resolution was significantly shorter in the combined polyphenol group (1.84 ± 0.72 days vs. 4.5 ± 1.36 days; p < 0.001). Similarly, time to return to school (3.21 ± 0.9 days vs. 5.8 ± 1.91 days; p < 0.001) and time for parents to return to work were significantly shorter in the combined polyphenol group (p < 0.001). The need for additional healthcare visits and antipyretic use was markedly lower in the combined polyphenol group (Day 3: 20.3% vs. 53.1%; Day 5: 0% vs. 15.6%; p < 0.001 for both comparisons). Repeated-measures analyses showed a significant time-by-group interaction, indicating that the reduction in symptom scores occurred more rapidly and prominently in the combined polyphenol group (p < 0.001). Treatment was generally well tolerated in the combined polyphenol group; no serious adverse events were reported, and parent-reported tolerability was high (9.39 ± 0.7). Conclusions: This multicenter retrospective real-world data study suggests that the use of a preparation containing polyphenol, vitamin D3, vitamin C, and zinc in addition to antiviral therapy was associated with shorter symptom duration, lower symptom severity scores, and faster functional recovery in children diagnosed with influenza. These findings suggest that this combination may represent a promising and well-tolerated adjunctive approach in the management of pediatric influenza. Full article

(This article belongs to the Special Issue The Development of Drug Delivery Systems and Pharmaceutical Formulations for the Treatment of Infectious Diseases)

14 pages, 1318 KB

Open AccessArticle

In Silico Studies and Biological Evaluation of Thiosemicarbazones as Cruzain-Targeting Trypanocidal Agents for Chagas Disease

by Lidiane Meier, Milena F. C. V. de Melo, Heitor R. Abreu, Isabella M. e Oliveira, Larissa Sens, Thiago H. Doring, Renata Krogh, Adilson Beatriz, Adriano D. Andricopulo, Sumbal Saba, Aldo S. de Oliveira and Jamal Rafique

Pharmaceutics 2026, 18(1), 65; https://doi.org/10.3390/pharmaceutics18010065 - 4 Jan 2026

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Abstract

Background/Objectives: Chagas disease remains a major unmet medical need due to the limited efficacy and safety of current therapies. Here, we investigated sixteen thiosemicarbazone (TSC) derivatives as cruzain inhibitors using an integrated in silico/in vitro workflow. Methods: Docking against cruzain (PDB 3KKU) guided hit prioritization and correlated with enzyme inhibition; validation by redocking supported the protocol’s reliability. Results: The top compounds—H7, H10 and H11—showed potent cruzain inhibition (IC₅₀ = 0.306, 0.512 and 0.412 µM, respectively) and low-micromolar trypanocidal activity, with negligible cytotoxicity in human fibroblasts (CC₅₀ > 64 µM) and favorable selectivity. Structure–activity insights highlighted the role of expanded aromatic systems and electron-donating groups in enhancing binding within S2/S1′ subsites, while nitro substituents were associated with higher cytotoxicity. In silico ADMET parameters supported oral drug-likeness and acceptable metabolic liabilities. Conclusions: Overall, these data position TSCs as promising anti-T. cruzi leads and underscore the value of rational design against cruzain. Full article

(This article belongs to the Special Issue The Development of Drug Delivery Systems and Pharmaceutical Formulations for the Treatment of Infectious Diseases)

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17 pages, 3633 KB

Open AccessArticle

New Copper (II) Complexes Based on 1,4-Disubstituted-1,2,3-Triazole Ligands with Promising Antileishmanial Activity

by João P. C. Nascimento, Natali L. Faganello, Karolina F. Freitas, Leandro M. C. Pinto, Amarith R. das Neves, Diego B. Carvalho, Carla C. P. Arruda, Sidnei M. Silva, Rita C. F. Almeida, Amilcar M. Júnior, Davi F. Back, Lucas Pizzuti, Sumbal Saba, Jamal Rafique, Adriano C. M. Baroni and Gleison A. Casagrande

Pharmaceutics 2026, 18(1), 64; https://doi.org/10.3390/pharmaceutics18010064 - 4 Jan 2026

Cited by 1 | Viewed by 1471

Abstract

Background/Objectives: Leishmaniasis constitutes one of the most fatal parasitic diseases globally, adversely impacting the health of individuals residing in both intertropical and temperate zones. In these geographical areas, the administration of treatment is often inconsistent and largely ineffective with the available pharmaceuticals, as these exhibit more pronounced side effects than the therapeutic advantages they purport to provide. Methods: Consequently, the current investigation seeks to engage in molecular modeling of novel pharmacological candidates incorporating 1,2,3 disubstituted triazole moieties, coordinated with Cu^II metal centers, in pursuit of promising bioactive properties. Results: Two complexes were prepared and X-ray analysis revealed a comparable structural configuration surrounding the copper (II) atom. The planar square coordination geometry was elucidated through the assessment of the

τ_{4} = 0

(tau four) parameters. The comprehensive characterization encompasses HRMS-ESI (+), NMR, elemental analyses, mid-infrared, and UV-vis spectroscopic techniques. Time-dependent density functional theory (TD-DFT) analyses will substantiate the findings obtained through UV-vis spectroscopy. Crucially, the biological assays against Leishmania (L.) amazonensis revealed that Complex 1 exhibited outstanding potency against the intracellular amastigote form, demonstrating a half-maximal inhibitory concentration (IC₅₀) of 0.4 µM. This activity was 6-fold higher than that of amphotericin B (IC₅₀ = 2.5 µM) and 33-fold higher than pentamidine (IC₅₀ = 13.3 µM). Furthermore, Complex 1 showed a promising selectivity index (SI = 9.7) against amastigotes, surpassing the reference drugs and meeting the criteria for a lead compound. While less active on promastigotes, both complexes demonstrated high stability in DMSO solution, a prerequisite for biological testing. Conclusions: These results unequivocally identify Complex 1 as a highly promising candidate for the development of new antileishmanial therapies, warranting further in vivo studies. Full article

(This article belongs to the Special Issue The Development of Drug Delivery Systems and Pharmaceutical Formulations for the Treatment of Infectious Diseases)

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16 pages, 4234 KB

Open AccessArticle

Protein-Based Electrospun Nanofibers Doped with Selenium Nanoparticles for Wound Repair

by Marco Ruggeri, Simone Marsani, Amedeo Ungolo, Barbara Vigani, Eleonora Bianchi, Cèsar Viseras, Silvia Rossi and Giuseppina Sandri

Pharmaceutics 2025, 17(10), 1276; https://doi.org/10.3390/pharmaceutics17101276 - 30 Sep 2025

Cited by 2 | Viewed by 1161

Abstract

Background/Objectives: The design of scaffolds that mimic the extracellular matrix has gained increasing attention in regenerative medicine. This study aims to develop and characterize electrospun nanofibrous scaffolds based on pullulan blended with either gelatin or gliadin and doped with selenium nanoparticles (Se NPs), to assess the influence of protein type and Se NP doping on scaffold performance and regenerative potential. Methods: Se NPs were synthesized via redox reaction and stabilized using pullulan. Electrospun scaffolds were then prepared by blending pullulan-stabilized Se NPs with either gelatin or gliadin. The resulting fibers were characterized using a multidisciplinary approach, including physicochemical (morphology, fiber dimension, swelling capacity, surface zeta potential, mechanical properties) and preclinical properties (antioxidant properties, fibroblast adhesion and proliferation, collagen expression). Results: Protein type influenced fiber morphology and dimensions, as well as mechanical behavior, with gelatin-based scaffolds demonstrating smaller fiber diameters and higher mechanical properties. The doping with Se NPs enhanced scaffold antioxidant properties without affecting fiber formation. Moreover, all scaffolds supported fibroblast proliferation, but those containing Se NPs showed enhanced modulation of ECM gene expression. Conclusions: The results show that scaffolds doped with Se NPs exhibited superior performance compared to the undoped counterparts, offering promising platforms for chronic wound reparation. Full article

(This article belongs to the Special Issue The Development of Drug Delivery Systems and Pharmaceutical Formulations for the Treatment of Infectious Diseases)

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24 pages, 2737 KB

Open AccessArticle

Antiviral Activity of Liposomes Containing Natural Compounds Against CHIKV

by Marília Freitas Calmon, Luiza Araújo Gusmão, Thalles Fernando Rocha Ruiz, Guilherme Rodrigues Fernandes Campos, Gabriela Miranda Ayusso, Tamara Carvalho, Isabella do Vale Francisco Bortolato, Pâmela Joyce Previdelli Conceição, Sebastião Roberto Taboga, Ana Carolina Gomes Jardim, Andres Merits, Paula Rahal and Antonio Claudio Tedesco

Pharmaceutics 2025, 17(9), 1229; https://doi.org/10.3390/pharmaceutics17091229 - 22 Sep 2025

Cited by 4 | Viewed by 1608

Abstract

Background/Objectives: Chikungunya virus (CHIKV), a mosquito-borne single-stranded RNA virus belonging to the genus Alphavirus (family Togaviridae), causes large-scale outbreaks. However, no specific treatment for CHIKV infections is currently available. Berberine and emodin are plant-derived compounds with anti-CHIKV activities. This study aimed to evaluate the antiviral efficacy of liposomes containing berberine (LB) or emodin (LE) against CHIKV in vitro, since nanocarriers incorporating zwitterionic polymers are known to enhance the biostability, biocompatibility, and therapeutic efficacy of drug candidates. Methods: Liposomes were synthesized and characterized, and cell viability was assessed to determine appropriate concentrations for subsequent assays. Confocal microscopy, antiviral assays, and western blotting were performed in BHK-21 and Huh7 cells. Results: In BHK-21 and Huh7 cells, LB and LE were well tolerated at concentrations of 5 and 10 µM, respectively. In both cell types, liposomes were internalized; LE was predominantly localized in the cytoplasm, whereas LB was also detected in the nucleus. EGCG, used as a standard drug against CHIKV in antiviral assays, exhibited virucidal activity and inhibited RNA replication and multiple stages of the CHIKV replication cycle in BHK-21 and Huh7 cells. Both the nanoformulations and EGCG consistently suppressed the expression of CHIKV replicase and virion proteins. Conclusions: These findings highlight the potential of berberine- and emodin-loaded liposomes as antiviral agents against CHIKV infection. Full article

(This article belongs to the Special Issue The Development of Drug Delivery Systems and Pharmaceutical Formulations for the Treatment of Infectious Diseases)

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19 pages, 2810 KB

Open AccessArticle

In Vitro Assessment of a Doubly Adjuvanted Self-Emulsified Nanoemulsion as a Delivery Vehicle for Antigenic Proteins

by Evgenia Tsanaktsidou, Maritsa Margaroni, Evdokia Karagouni, Costas Kiparissides and Olga Kammona

Pharmaceutics 2025, 17(7), 870; https://doi.org/10.3390/pharmaceutics17070870 - 2 Jul 2025

Cited by 2 | Viewed by 3886

Abstract

Background/Objectives: Leishmaniasis is a prevailing infectious disease transmitted via infected phlebotomine sandflies. The lack of an efficient vaccine with respect to immunogenic antigens and adjuvanted delivery systems impedes its control. Following the induction of immune responses in mice vaccinated with multi-epitope Leishmania peptides (LeishPts) encapsulated in doubly adjuvanted self-nanoemulsifying drug delivery systems (ST-SNEDDSs), this study aims to assess ST-SNEDDS-based nanoemulsions as vehicles for the delivery of antigenic proteins. Methods: Model antigens (e.g., BSA-FITC, OVA) were encapsulated in ST-SNEDDS after being complexed with the cationic phospholipid dimyristoyl phosphatidylglycerol (DMPG) via hydrophobic ion pairing. The nanoemulsions were characterized with respect to droplet diameter, zeta potential, stability, protein loading, protein release from the nanodroplets in different release media and cell uptake. Results: Both model antigens exhibited high encapsulation efficiency (>95%) and their release from the nanodroplets was shown to be strongly affected by the type of release medium (e.g., PBS, FBS 10% v/v) and the ratio of its volume to that of the oily phase, in agreement with predictions of protein release. Protein-loaded nanoemulsion droplets labeled with Cy-5 were found to be efficiently taken up by macrophages (J774A.1) in vitro. However, no colocalization of the labeled nanodroplets and BSA-FITC could be observed. Conclusions: It was revealed that in contrast with LeishPts, whole protein molecules may not be appropriate antigenic cargo for ST-SNEDDS formulations due to the rapid protein release from the nanodroplets in release media simulating in vitro culture and in vivo conditions such as FBS 10% v/v. Full article

(This article belongs to the Special Issue The Development of Drug Delivery Systems and Pharmaceutical Formulations for the Treatment of Infectious Diseases)

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