Search Results (27)

The recent advancement of 3D-printed drugs is an emerging technology that has the potential for effective and safe oral delivery of personalized treatment regimens to patients, replacing the current “one size fits all” philosophy. The objective of this literature review is to highlight the importance of 3D-printing technology in the development of personalized treatments, focusing on Levetiracetam, the first FDA-approved 3D-printed drug, for the treatment of epilepsy. Levetiracetam serves as an ideal paradigm for exploring how precision medicine and 3D printing can be applied to improve treatment outcomes for other complex diseases such as diabetes, cardiovascular diseases, and cancer. 3D printing enables precise dosage and time-release profiles by modifying factors such as shape and size, and the combination of active pharmaceutical ingredients (APIs) and excipients, ensuring consistent therapeutic levels over the treatment period. Design of oral tablets with multiple compartments allows for simultaneous treatment with multiple APIs, each one with a different release profile, minimizing drug–drug interactions and side effects. This technology also supports on-demand production, making it particularly beneficial in resource-limited or urgent situations, and offers the flexibility to customize dosage forms. Additive manufacturing could be an important tool for developing personalized treatments to address the diverse medical needs of patients with complex diseases. Therefore, there is a need for more 3D-printed FDA-approved drugs in the biopharmaceutical industry to enable personalized treatment, improved patient compliance, and precise drug release control. Full article

Mesoporous silica nanoparticles (MSNs) are gaining popularity in nanomedicine due to their large surface area, variable pore size, great biocompatibility, and chemical adaptability. In recent years, the combination of smart polymeric materials with MSNs has transformed the area of regulated drug administration, particularly under stimuli-responsive settings. Polymer-modified MSNs provide increased stability, longer circulation times, and, most crucially, the capacity to respond to diverse internal (pH, redox potential, enzymes, and temperature) and external (light, magnetic field, and ultrasonic) stimuli. These systems allow for the site-specific, on-demand release of therapeutic molecules, increasing treatment effectiveness while decreasing off-target effects. This review presents a comprehensive analysis of recent advancements in the development and application of polymer-functionalized MSNs for stimuli-triggered drug delivery. Key polymeric modifications, including thermoresponsive, pH-sensitive, redox-responsive, and enzyme-degradable systems, are discussed in terms of their design strategies and therapeutic outcomes. The synergistic use of dual or multiple stimuli-responsive polymers is also highlighted as a promising avenue to enhance precision and control in complex biological environments. Moreover, the integration of targeting ligands and stealth polymers such as PEG further enables selective tumor targeting and immune evasion, broadening the potential clinical applications of these nanocarriers. Recent progress in stimuli-triggered MSNs for combination therapies such as chemo-photothermal and chemo-photodynamic therapy is also covered, emphasizing how polymer modifications enhance responsiveness and therapeutic synergy. Finally, the review discusses current challenges, including scalability, biosafety, and regulatory considerations, and provides perspectives on future directions to bridge the gap between laboratory research and clinical translation. Full article

Wound healing is a complex, tightly regulated process essential for maintaining skin barrier function. Chronic wounds, often complicated by biofilm-forming bacteria and elevated oxidative stress, pose significant challenges in clinical management. The rise of antibiotic-resistant bacteria has further exacerbated the problem, limiting therapeutic options and complicating wound treatment. Traditional wound care approaches frequently fail to provide real-time accurate insights into wound status, leading to delayed or suboptimal treatments. Recent advancements in modern and smart wound dressings, which integrate various biosensors, different new drug delivery systems, and wireless communication technology, offers promising solutions for monitoring wound progression over time. These innovations enable early detection of adverse events such as bacterial infections and inflammation, facilitating more effective, on-demand treatment. This review highlights the current state of antibiotic-embedded wound dressings, discusses their limitations, and explores the potential of next-generation wound dressings incorporating microelectronic sensors for real-time monitoring and adaptive therapeutic responses to support healing and combat antimicrobial resistance. Full article

Hydrogels are three-dimensional polymeric systems, being able to accommodate different categories of bioactive agents and act as promising drug delivery systems in many different biomedical applications. Due to their extended 3D network, hydrogels exhibit many advantages, such as extensive loading capacity and controlled drug release profiles, combined with characteristics such as biocompatibility and biodegradability, due to their constructive polymeric biomaterials. Moreover, hydrogels are capable of being administered via different routes of administration, including systemic and topical ones, due to their tunable characteristics. Stimuli-responsive hydrogels are characterized as smart biomaterials, while environmental stimuli, such as pH, can be employed to trigger on-demand drug release from the hydrogels via the provocation of conformational changes. In the present study, an emphasis on the pH-responsive hydrogels is taking place through various literature cases in drug delivery, wound healing, and some alternative applications, including implantation, oral administration, etc., wherein many different polymeric derivatives have been utilized. Moreover, the role of each used polymer or polymeric combination with other functional biomaterials, their mode of structure formation (for example, crosslinking), and their content release mechanism are highlighted, as well as the therapeutic effect of the hydrogels on different pathological conditions, as promising candidates for pharmaceutical applications. Full article

The hyperglycemic microenvironment in diabetic wounds predisposes them to bacterial infections, sustains chronic inflammation, and hinders therapeutic efficacy. In this study, antibiotic-loaded fast-crosslinked hybrid nanogel wound dressings (florfenicol nanogels) based on Schiff’s base bond were obtained through N, O-carboxymethyl chitosan (N, O-CMCS) and oxidized hyaluronic acid (OHA). The successfully prepared florfenicol N, O-CMCS/OHA nanogels exhibited obvious pH- and HAase-responsiveness release, which allowed it to quickly release florfenicol at infected wounds to exert on-demand antibacterial activity, as well as accelerate diabetic bacterial-infected wound healing. The nanogel dressings showed excellent antibacterial activity by destroying the bacterial cell membrane and wall. More specifically, the glucose oxidase in the dressings can catalyze the breakdown of high-concentration glucose, generating abundant ROS that directly cause cellular damage. According to the results of wound healing, the dressings showed satisfactory anti-inflammatory and therapeutic effects for the full-thickness mouse skin defect wounds. The nanogel dressings are anticipated to be excellent wound dressings to synergistically overcome the theraputic difficulty of diabetic bacterial wounds. Full article

The rational design of multifunctional drug delivery systems capable of achieving precise drug release remains a huge challenge. Herein, we designed a stimuli-responsive dendritic-DNA-based nanohydrogel as a nanocarrier to achieve the co-delivery of doxorubicin and HMGN5 mRNA-targeting antisense oligonucleotides, thus achieving dual therapeutic effects. The nanocarrier, constructed from dendritic DNA with three crosslinking branches and one loading branch, formed biocompatible and programmable DNA nanohydrogels. The C-rich sequences in the crosslinking branches conferred pH sensitivity, while the loading strand enabled efficient incorporation of a shielding DNA/ASO complex. DOX encapsulation yielded a chemo–gene co-delivery platform. Upon cellular uptake by cancer cells, the nanocarrier disassembled in the acidic tumor microenvironment, releasing DOX for chemotherapy and ASOs via toehold-mediated strand displacement (TMSD) for targeted gene silencing. Cellular studies demonstrated significantly enhanced cancer cell inhibition compared to single-agent treatments, highlighting strong combined effects. This study provides a novel strategy for tumor-microenvironment-responsive co-delivery, enabling precise, on-demand release of therapeutic agents to enhance combined chemo–gene therapy. Full article

Liposome-based drug delivery technologies have showed potential in enhancing medication safety and efficacy. Innovative drug loading and release mechanisms highlighted in this review of next-generation liposomal formulations. Due to poor drug release kinetics and loading capacity, conventional liposomes have limited clinical use. Scientists have developed new liposomal carrier medication release control and encapsulation methods to address these limits. Drug encapsulation can be optimized by creating lipid compositions that match a drug’s charge and hydrophobicity. By selecting lipids and adding co-solvents or surfactants, scientists have increased drug loading in liposomal formulations while maintaining stability. Nanotechnology has also created multifunctional liposomes with triggered release and personalized drug delivery. Surface modification methods like PEGylation and ligand conjugation can direct liposomes to disease regions, improving therapeutic efficacy and reducing off-target effects. In addition to drug loading, researchers have focused on spatiotemporal modulation of liposomal carrier medication release. Stimuli-responsive liposomes release drugs in response to bodily signals. Liposomes can be pH- or temperature-sensitive. To improve therapeutic efficacy and reduce systemic toxicity, researchers added stimuli-responsive components to liposomal membranes to precisely control drug release kinetics. Advanced drug delivery technologies like magnetic targeting and ultrasound. Pro Drug, RNA Liposomes approach may improve liposomal medication administration. Magnetic targeting helps liposomes aggregate at illness sites and improves drug delivery, whereas ultrasound-mediated drug release facilitates on-demand release of encapsulated medicines. This review also covers recent preclinical and clinical research showing the therapeutic promise of next-generation liposomal formulations for cancer, infectious diseases, neurological disorders and inflammatory disorders. The transfer of these innovative liposomal formulations from lab to clinical practice involves key difficulties such scalability, manufacturing difficulty, and regulatory limits. Full article

Background: Achieving a balance between stable drug loading/delivery and on-demand drug activation/release at the target sites remains a significant challenge for nanomedicines. Carrier-free prodrug nanoassemblies, which rely on the design of prodrug molecules, offer a promising strategy to optimize both drug delivery efficiency and controlled drug release profiles. Methods: A library of doxorubicin (DOX) prodrugs was created by linking DOX to fatty alcohols of varying chain lengths via a tumor-responsive disulfide bond. In vitro studies assessed the stability and drug release kinetics of the nanoassemblies. In vivo studies evaluated their drug delivery efficiency, tumor accumulation, and antitumor activity in mouse models. Results: In vitro results demonstrated that longer fatty alcohol chains improved the stability of the nanoassemblies but slowed down the disassembly and drug release process. DSSC16 NAs (hexadecanol-modified DOX prodrug) significantly prolonged blood circulation time and enhanced tumor accumulation, with AUC values 14.2-fold higher than DiR Sol. In 4T1 tumor-bearing mouse models, DSSC16 NAs exhibited notably stronger antitumor activity, resulting in a final mean tumor volume of 144.39 ± 36.77 mm³, significantly smaller than that of all other groups (p < 0.05 by ANOVA at a 95% confidence interval). Conclusions: These findings underscore the critical role of prodrug molecule design in the development of effective prodrug nanoassemblies. The balance between stability and drug release is pivotal for optimizing drug delivery and maximizing therapeutic efficacy. Full article

Conventional cancer chemotherapy often struggles with safely and effectively delivering anticancer therapeutics to target tissues, frequently leading to dose-limiting toxicity and suboptimal therapeutic outcomes. This has created a need for novel therapies that offer greater efficacy, enhanced safety, and improved toxicological profiles. Nanocarriers are nanosized particles specifically designed to enhance the selectivity and effectiveness of chemotherapy drugs while reducing their toxicity. A subset of drug delivery systems utilizes stimuli-responsive nanocarriers, which enable on-demand drug release, prevent premature release, and offer spatial and temporal control over drug delivery. These stimuli can be internal (such as pH and enzymes) or external (such as ultrasound, magnetic fields, and light). This review focuses on the mechanics of ultrasound-induced drug delivery and the various nanocarriers used in conjunction with ultrasound. It will also provide a comprehensive overview of key aspects related to ultrasound-induced drug delivery, including ultrasound parameters and the biological effects of ultrasound waves. Full article

Recent advancements in brain stimulation and nanomedicine have ushered in a new era of therapeutic interventions for psychiatric and neurodegenerative disorders. This review explores the cutting-edge innovations in brain stimulation techniques, including their applications in alleviating symptoms of main neurodegenerative disorders and addiction. Deep Brain Stimulation (DBS) is an FDA-approved treatment for specific neurodegenerative disorders, including Parkinson’s Disease (PD), and is currently under evaluation for other conditions, such as Alzheimer’s Disease. This technique has facilitated significant advancements in understanding brain electrical circuitry by enabling targeted brain stimulation and providing insights into neural network function and dysfunction. In reviewing DBS studies, this review places particular emphasis on the underlying main neurotransmitter modifications and their specific brain area location, particularly focusing on the dopaminergic system, which plays a critical role in these conditions. Furthermore, this review delves into the groundbreaking developments in nanomedicine, highlighting how nanotechnology can be utilized to target aberrant signaling in neurodegenerative diseases, with a specific focus on the dopaminergic system. The discussion extends to emerging technologies such as magnetoelectric nanoparticles (MENPs), which represent a novel intersection between nanoformulation and brain stimulation approaches. These innovative technologies offer promising avenues for enhancing the precision and effectiveness of treatments by enabling the non-invasive, targeted delivery of therapeutic agents as well as on-site, on-demand stimulation. By integrating insights from recent research and technological advances, this review aims to provide a comprehensive understanding of how brain stimulation and nanomedicine can be synergistically applied to address complex neuropsychiatric and neurodegenerative disorders, paving the way for future therapeutic strategies. Full article

Small interfering RNA (siRNA) therapeutics, characterized by high specificity, potency, and durability, hold great promise in the treatment of cancer and other diseases. However, the clinic implementation of siRNA therapeutics critically depends on the safe and on–demand delivery of siRNA to the target cells. Here, we reported a family of ferrocenyl amphiphilic dendrimers (Fc-AmDs) for on–demand delivery of siRNA in response to the high ROS content in cancer cells. These dendrimers bear ROS–sensitive ferrocene moieties in the hydrophobic components and positively chargeable poly(amidoamine) dendrons as the hydrophilic entities, possessing favorable safety profiles and ROS responsive properties. One of these ferrocenyl amphiphilic dendrimers, Fc-C₈-AmD 8A, outperforms in siRNA delivery, benefiting from its optimal balance of hydrophobicity and hydrophilicity. Its ROS feature facilitates specific and efficient disassembly of its complex with siRNA in ROS–rich cancer cells for effective siRNA delivery and gene silencing. Moreover, Fc-C₈-AmD 8A also integrates the features and beneficial properties of both lipid and dendrimer vectors. Therefore, it represents a novel on–demand delivery system for cancer cell–specific siRNA delivery. This work opens new perspectives for designing self–assembly nanosystems for on–demand drug delivery. Full article

In recent years, nanocarriers have played an ever-increasing role in clinical and biomedical applications owing to their unique physicochemical properties and surface functionalities. Lately, much effort has been directed towards the development of smart, stimuli-responsive nanocarriers that are capable of releasing their cargos in response to specific stimuli. These intelligent-responsive nanocarriers can be further surface-functionalized so as to achieve active tumor targeting in a sequential manner, which can be simply modulated by the stimuli. By applying this methodological approach, these intelligent-responsive nanocarriers can be directed to different target-specific organs, tissues, or cells and exhibit on-demand controlled drug release that may enhance therapeutic effectiveness and reduce systemic toxicity. Light, an external stimulus, is one of the most promising triggers for use in nanomedicine to stimulate on-demand drug release from nanocarriers. Light-triggered drug release can be achieved through light irradiation at different wavelengths, either in the UV, visible, or even NIR region, depending on the photophysical properties of the photo-responsive molecule embedded in the nanocarrier system, the structural characteristics, and the material composition of the nanocarrier system. In this review, we highlighted the emerging functional role of light in nanocarriers, with an emphasis on light-responsive liposomes and dual-targeted stimuli-responsive liposomes. Moreover, we provided the most up-to-date photo-triggered targeting strategies and mechanisms of light-triggered drug release from liposomes and NIR-responsive nanocarriers. Lastly, we addressed the current challenges, advances, and future perspectives for the deployment of light-responsive liposomes in targeted drug delivery and therapy. Full article

Bacterial infection is currently considered to be one of the major reasons that leads to the failure of guided bone regeneration (GBR) therapy. Under the normal condition, the pH is neutral, while the microenvironment will become acid at the sites of infection. Here, we present an asymmetric microfluidic/chitosan device that can achieve pH-responsive drug release to treat bacterial infection and promote osteoblast proliferation at the same time. On-demand release of minocycline relies on a pH-sensitive hydrogel actuator, which swells significantly when exposed to the acid pH of an infected region. The PDMAEMA hydrogel had pronounced pH-sensitive properties, and a large volume transition occurred at pH 5 and 6. Over 12 h, the device enabled minocycline solution flowrates of 0.51–1.63 µg/h and 0.44–1.13 µg/h at pH 5 and 6, respectively. The asymmetric microfluidic/chitosan device exhibited excellent capabilities for inhibiting Staphylococcus aureus and Streptococcus mutans growth within 24 h. It had no negative effect on proliferation and morphology of L929 fibroblasts and MC3T3-E1 osteoblasts, which indicates good cytocompatibility. Therefore, such a pH-responsive drug release asymmetric microfluidic/chitosan device could be a promising therapeutic approach in the treatment of infective bone defects. Full article

Enrofloxacin has a poor palatability and causes strong gastric irritation; the oral formulation of enrofloxacin is unavailable, which limits the treatment of Escherichia coli (E. coli) infections via oral administration. To overcome the difficulty in treating intestinal E. coli infections, an oral intelligent-responsive chitosan-oligosaccharide (COS)–sodium alginate (SA) composite core-shell nanogel loaded with enrofloxacin was explored. The formulation screening, characteristics, pH-responsive performance in gastric juice and the intestinal tract, antibacterial effects, therapeutic effects, and biosafety level of the enrofloxacin composite nanogels were investigated. The optimized concentrations of COS, SA, CaCl₂, and enrofloxacin were 8, 8, 0.2, and 5 mg/mL, respectively. The encapsulation efficiency, size, loading capacity, zeta potential, and polydispersity index of the optimized formulation were 72.4 ± 0.8%, 143.5 ± 2.6 nm, 26.6 ± 0.5%, −37.5 ± 1.5 mV, and 0.12 ± 0.07, respectively. Scanning electron microscopy images revealed that enrofloxacin-loaded nanogels were incorporated into the nano-sized cross-linked networks. Fourier transform infrared spectroscopy showed that the nanogels were prepared by the electrostatic interaction of the differently charged groups (positive amino groups (-NH₃⁺) of COS and the negative phenolic hydroxyl groups (-COO⁻) of SA). In vitro, pH-responsive release performances revealed effective pH-responsive performances, which can help facilitate targeted “on-demand” release at the target site and ensure that the enrofloxacin has an ideal stability in the stomach and a responsive release in the intestinal tract. The antibacterial activity study demonstrated that more effective bactericidal activity against E. coli could have a better treatment effect than the enrofloxacin solution. Furthermore, the enrofloxacin composite nanogels had great biocompatibility. Thus, the enrofloxacin composite core-shell nanogels might be an oral intelligent-responsive preparation to overcome the difficulty in treating intestinal bacterial infections. Full article

Multifunctional theranostic nanomaterial represents one type of emerging agent with the potential to offer both sensitive diagnosis and effective therapy. Herein, we report a novel drug/siRNA co-delivery nanocarrier, which is based on fluorescent mesoporous core-shell silica nanoparticles coated by cross-linked polyethylenimine. The fluorescent mesoporous core-shell silica nanoparticles can provide numerous pores for drug loading and negative charged surface to assemble cross-linked polyethylenimine via electrostatic interaction. Disulfide cross-linked polyethylenimine can be absorbed on the surface of silica nanoparticles which provide the feasibility to bind with negatively charged siRNA and release drug “on-demand”. In addition, the hybrid nanoparticles can be easily internalized into cells to realize drug/siRNA co-delivery and therapeutic effect imaging. This work would stimulate interest in the use of self-assembled cross-linked polyethylenimine with fluorescent mesoporous core-shell silica nanoparticles to construct multifunctional nanocomposites for tumor therapy. Full article