Current drug delivery最新文献

3D printing, also known as additive manufacturing, has transformed drug delivery by enabling the development of complex, patient-specific dosage forms and implantable systems tailored to individual therapeutic needs. This review explores the convergence of 3D printing technologies with nanomaterials in the fabrication of advanced drug delivery systems and biomedical implants. Key 3D printing techniques, including Fused Deposition Modeling (FDM), Stereolithography (SLA), Direct Energy Deposition (DED), and electrospinning, are discussed alongside their material compatibilities, such as polymers, metals, ceramics, and composites. Nanomaterials-like dendrimers, liposomes, polymeric nanoparticles, carbon nanotubes, and exosomes-are critically examined for their roles in enhancing drug stability, targeted delivery, and controlled release. The paper highlights innovative drug delivery strategies, including polypills, gastro-floating tablets, and compartmentalized dosage systems, enabled by precise 3D printing. Additionally, recent advancements in 3D-printed drugeluting implants for localized therapy in cancer and infectious diseases are presented. These systems demonstrate prolonged release profiles, biocompatibility, and mechanical properties resembling those of human tissue. Despite scaling and regulatory challenges, the future of this technology lies in the integration of smart materials, surface-modified nanoparticles, and AI-assisted design, paving the way for decentralized, personalized, and sustainable medical solutions.

Neurodegenerative diseases (NDs) are characterized by slow progression and late detection, seriously compromising the efficiency of treatments. The presence of the blood-brain barrier (BBB) significantly impairs conventional therapies. More recently, extracellular vesicles (EVs) have emerged as promising drug delivery systems for brain-targeted therapies due to their ability to cross the BBB and their combination of low immunogenicity, high biocompatibility, and delivery efficiency. EVs play a vital role in intercellular communication, transporting nucleic acids, lipids, and proteins between cells, which are crucial for modulating cellular functions, immune responses, and neuroprotection. They have also demonstrated considerable therapeutic potential by mitigating neuroinflammation, reducing neuronal damage, and alleviating cognitive deficits in preclinical models of NDs. This review discusses various applications of EVs in the treatment of NDs, challenges they present as a delivery vehicle, and future research directions and regulatory considerations in advancing EV-based therapies for neurodegenerative disorders.

Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease leading to cartilage degeneration and destruction. Friction between articular cartilage surfaces exacerbates these effects. Currently, clinical therapy is dominated by single anti-inflammatory or lubrication treatments. Preparations with both anti-inflammatory and lubrication effects are of great significance for RA treatment. In this study, a mesoporous silica nanosystem (MSN@DCF-HA) with dual functions of anti-inflammation and joint lubrication was developed for RA therapy.

Methods: Mesoporous silica nanoparticles (MSN) were prepared by the template method. MSN@DCF-HA was synthesized by encapsulating diclofenac (DCF) into MSN and then coating it with hyaluronic acid (HA). Drug loading capacity, encapsulation efficiency, in vitro release, and biosafety of MSN@DCF-HA were evaluated. An RA rat inflammation model was used to assess therapeutic efficacy.

Results: TEM revealed that MSN@DCF-HA was spherical and size-uniform. Experiments demonstrated favorable biocompatibility and stability. The system facilitated sustained DCF release in acidic PBS. In vivo results showed significant reduction in paw swelling, inflammatory factors, and bone damage in the MSN@DCF-HA group. Cell toxicity experiments, hemolysis experiments, and in vivo experiments indicated that it has no significant toxicity.

Discussion: MSN@DCF-HA, by loading DCF to exert anti-inflammatory effects and HA to provide external lubrication, joint protection, and synergistic treatment of RA, has demonstrated excellent therapeutic effects, providing a new strategy for RA treatment.

Conclusion: MSN@DCF-HA was successfully prepared, exhibited slow drug release in acidic environments, and its anti-inflammation and joint lubrication exerted synergistic effects on RA rats without obvious toxicity. This work proposes a novel therapeutic strategy for rheumatoid arthritis.

Introduction: The toxicity of nontargeted chemotherapy hinders liver cancer treatment. This study developed dual-peptide (SP94/TAT) co-modified liposomes (SP94/TAT-DOX/DTX-LPs) for enhanced targeting and efficacy.

Methods: Liposomes encapsulating docetaxel (DTX) and doxorubicin (DOX) were prepared via film dispersion/ammonium sulfate gradient using DSPE-PEG, lecithin, and cholesterol. SP94 (targeting) and TAT (penetrating) peptides were conjugated via organic phase reaction/insertion. Their physicochemical properties, encapsulation efficiency, stability, drug release, and in vitro antitumor activity were evaluated.

Results: Optimized SP94/TAT-DOX/DTX-LPs were spherical (119.6 ± 4.1 nm; PDI 0.161 ± 0.006; zeta -9.84 ± 1.54 mV), and their encapsulation efficiency was high (DOX: 92.97 ± 1.73%; DTX: 80.33 ± 0.96%). Stability was confirmed at 4 °C for 30 days (PDI < 0.2, size change < 10%) and in 50% fetal bovine serum (FBS) for 24 hours (transmittance > 90%). Sustained release showed 68.2 ± 3.5% (DTX) and 74.8 ± 2.9% (DOX) cumulative release at 48h (PBS pH 7.4). In vitro, SP94/TATDOX- LPs showed 2.3-fold higher HepG2 cellular uptake versus single-modified liposomes (p<0.001), with minimal LO2 uptake. Cytotoxicity assays revealed a 3.11-fold lower IC50 (0.096 ± 0.026 μg/mL) versus unmodified liposomes (0.299 ± 0.103 μg/mL). Apoptosis was significantly higher (39.5% in HepG2) than in single-modified formulations (20.55-26.74%).

Discussion: SP94/TAT-LPs enable dual-stage targeting: SP94 targets liver cancer cells, and TAT enhances penetration, significantly improving in vitro antitumor activity. Study limitations include sole in vitro validation (HepG2/LO2), small sample size (n=3), parameter variability, and lack of in vivo data on targeting, pharmacokinetics, and toxicity.

Conclusion: SP94/TAT-DOX/DTX-LPs achieved effective dual-stage targeting and synergistic cytotoxicity. High encapsulation, stability, and sustained release support their potential as a targeted platform for liver cancer therapy, reducing off-target toxicity.

Introduction: Prostate cancer is the most common cancer among men globally. The firstline drug, cabazitaxel (CTX), has significant side effects such as neutropenia and anemia. To address this, we aimed to develop hyaluronic acid (HA)-modified human serum albumin (HSA)-loaded CTX nanoparticles (HA-CTX NPs) to target prostate tumors with enhanced efficacy and reduced toxicity.

Methods: HA-CTX NPs were synthesized via a self-assembly method and optimized using unidirectional and response surface analyses. The NPs were characterized by particle size, zeta potential, and morphology. In vitro experiments evaluated the pharmacokinetics, cytotoxicity, and cellular uptake in prostate cancer cells with high CD44 expression and in HepG-2 cells with low CD44 expression. In vivo anti-tumor efficacy and biosafety were assessed using tumor-bearing models.

Results: The optimized HA-CTX NPs achieved an encapsulation efficiency of 89.2 ± 1.3%. Disulfide bonds enabled rapid drug release in the tumor microenvironment with high glutathione levels. In vitro studies showed significant cytotoxicity and targeting ability for prostate cancer cells. In vivo assays demonstrated a tumor inhibition rate of 85.31% with good biosafety.

Discussion: HA-CTX NPs exhibited superior anti-tumor efficacy and biosafety compared to Jevtana ®. The targeting ability was attributed to the high CD44 expression in prostate cancer cells. The rapid drug release in the tumor microenvironment contributed to the enhanced therapeutic effect. Limitations include the need for further long-term safety studies.

Conclusion: HA-CTX NPs represent a promising nanomedicine for prostate tumor treatment, offering improved efficacy and reduced side effects compared to conventional CTX formulations.

Introduction: Frankincense Essential Oil (FREO) has demonstrated curative potential in Ulcerative Colitis (UC) patients. However, the inherent instability of FREO results in its relatively low bioavailability. Therefore, the present study aimed to develop a novel oral O/W type FREO Submicron Emulsion Formulation (FREO-SE). This was achieved by encapsulating FREO within submicron emulsion droplets, with the further objective of elucidating the anti-UC efficacy of FREOSE.

Methods: A single-factor experimental approach was employed to screen the formulation, dosage, and preparation process of FREO-SE. Subsequently, the Box-Behnken Design (BBD) was utilized to optimize the submicron emulsion preparation procedure. The quality of the prepared emulsion was evaluated. Finally, a comparative analysis of the anti-ulcerative colitis efficacies of FREO and FREOSE was conducted using a UC mouse model. The mechanism of action of FREO-SE was further examined through immunohistochemistry, with the ultimate goal of enhancing the stability of FREO and elucidating its therapeutic effects on ulcerative colitis.

Results: The optimal formulation and manufacturing process for FREO-SE were established, and the particle size, PDI, and Zeta potential were characterized, with values of 105.09 ± 1.27 nm, 0.30 ± 0.02, and -37.43 ± 0.97 mV, respectively, confirming the successful preparation of FREO-SE. In DSS-induced UC mice, FREO-SE significantly reduced the DAI score compared with the DSS group. The weight loss of the FREO-SE-H group mice was significantly reduced (p < 0.001), and the shortening of colon length was significantly reduced (p < 0.001). Serum TNF-α and IL-6 levels were significantly reduced (p < 0.001), thereby alleviating colonic tissue lesions. The expression of p-ERK and p-P65 in colon tissue was significantly reduced (p < 0.001). In conclusion, FREO-SE inhibited the levels of p-ERK and p-P65 in MAPK and NF-κB signaling, and demonstrated a definite therapeutic effect in a mouse model of ulcerative colitis.

Discussion: This study confirmed that the FREO-SE formulation notably potentiates the therapeutic efficacy of FREO against UC, with its mechanism underlying modulation of the MAPK/NF-κB inflammatory signaling pathway.

Conclusion: The preparation process of FREO-SE is characterized by stability, simplicity, and controllability, endowing it with excellent stability. FREO-SE exhibits a protective effect against DSSinduced UC in mice and demonstrates significant efficacy in the ulcerative colitis mouse model.

Introduction: Vitis vinifera L. seed oil, Trigonella foenum-graecum L. seed oil, and the Olea europaea L. oil macerates of Helichrysum italicum (Roth) G. flowers and Matricaria recutita L. flowers were used for the preparation of topical wound-healing ointments.

Methods: The ointments basically were prepared by hot-melt blending method and subjected to rheological tests and texture profile analysis. After characterization of in vitro characterization studies, a scratch assay was conducted to evaluate the efficacy of ointment formulations. Ultimately, the optimized formulations underwent further testing on an in vivo burn wound model in mice.

Results: Measured viscosity values were F1:382.98 Pa.s and F2:2562.3 Pa.s, respectively, and both of the formulations created an easy-to-apply, soft, thin adhesive film layer. The fast wound closure was observed with F1 formulation, and when applied at different doses of 100 μL, 200 μL, and 400 μL, the 200 μL concentration of F1 formulation was able to heal the wound totally (100 %) at 48th hour.

Discussion: The F1 formulation presented lower viscosity than the F2; the increase in the white petrolatum concentration increased the initial viscosity as expected. F1 formulation had higher phyto-actives and cera alba and lower petrolatum in comparison to F2. The wound healing effects of both the formulations were synergistic due to their phytoactives content. In in vivo studies, the F1 ointment exhibited faster re-epithelialization with less inflammation compared to the burn control group.

Conclusion: The best formulation included oils of H. italicum, M. recutita, V. vinifera, and T. foenum-graecum at a total concentration of 16%, exhibiting appropriate preadability and successful healing property. Additional research needs to be carried out to shed light on the mechanism underlying the formulation's healing capabilities.

Introduction: One of the primary causes of severe vision loss globally is age-related macular degeneration (AMD), and the mainstay of therapies for neovascular diseases is intravenous administration of anti-VEGF (vascular endothelial growth factor) drugs. The goal of this research is to create an effective delivery of anti-VEGF drugs to overcome the challenges associated with current therapy and adverse effects arising from repetitive intravitreal injections.

Methods: Pazopanib (PZ) nanoparticles (NPs) have been generated to deliver the anti-VEGF drug to the posterior segment of the eye over an extended period via intravitreal injection. They were subsequently investigated for physicochemical and in vitro studies.

Results: The PZ NPs were found to be nano-sized with a particle size of 132.1 ± 1.4 nm and a PDI of 0.125 ± 0.023. The results showed that the zeta potential was -20.12 ± 2.7 mV and the entrapment efficiency was 33.9 ± 2.5%. Up to seven days of controlled drug release was observed in an in vitro drug release study. The PZ NPs were further assessed for cell cytotoxicity, cellular uptake, and anti- VEGF assays in in vitro cell culture investigations employing human retinal pigment epithelium cells (ARPE-19). In vitro cell culture tests revealed that, in comparison to the drug solution, the PZ NPs formulation was well taken up by the cells and less cytotoxic, as well as exhibited greater antiangiogenic efficacy by inhibiting VEGF expression for an extended period of time.

Discussion: The NPs demonstrated sustained drug release, driven by their controlled degradation kinetics. Increased potential intensity enhanced electrostatic repulsion, thereby improving NP stability. The low entrapment efficiency of PZ in the NPs was likely due to drug diffusion during emulsification and poor compatibility with the hydrophilic polymer matrix. For in vitro studies, ARPE-19 cells were selected due to their retinal pigment epithelial (RPE)-like properties, making them suitable for AMD drug testing. Efficacy (ELISA) assessments revealed that NP formulations had a stronger inhibitory effect than free drug solutions.

Conclusion: The proposed PZ NPs were successfully developed, characterized, and demonstrated potential application in the treatment of AMD.

Background: The ethanol extract of Pueraria lobatae Radix (EPL), a kind of medicinal herb powder with unacceptable behaviour (poor compactibility and slow dissolution rate), has the potential to be improved by double particle surface design by fluid-bed coating. This involves surface coating with plastic Hydroxypropyl Methylcellulose (HPMC) and surface pore formation induced by NH4HCO3.

Methods: The EPL drug was selected as the model for investigation. The formulation of the Composite Particles (CPs) was optimized using a central composite design. Subsequently, the pivotal tabletrelated attributes were contrasted between the optimized porous HPMC-coated EPL CPs and the pure HPMC-coated EPL CPs. Finally, the stability and applicability of the porous HPMC-coated EPL CPs were studied.

Results: The results demonstrated that (i) the optimized use levels of HPMC and NH4HCO3 for the porous CPs were 8.42% and 15.00% (w/w), respectively; (ii) the compactibility and tablet dissolution rate of the porous HPMC-coated EPL CPs were significantly enhanced in comparison to those produced from the pure HPMC-coated CPs; and (iii) the porous HPMC-coated CPs exhibited good stability and universal applicability in direct compaction.

Conclusion: As a whole, the combination of polymeric coating and porous design proved effective in enhancing the compactibility and dissolution rate of EPL-based CPs while also rendering them suitable for direct compaction. These findings are conducive to the expansion of the application of fluidbed coating technology and the simultaneous improvement of the quality and efficacy of some drug tablets.