High Drug Loading Capacity Research Articles

Development and characterization of a self-nano emulsifying drug delivery system (SNEDDS) for Ornidazole to improve solubility and oral bioavailability of BCS class II drugs.

This study aimed to investigate the in vitro performance of self-nanoemulsifying drug delivery systems (SNEDDSs) of Ornidazole (ORD), a poorly water-soluble drug. Self-nanoemulsifying drug delivery systems of ORD were prepared using various oils, non-ionic surfactants, and/or water-soluble co-solvents and assessed visually/by droplet size measurement. Equilibrium solubility of ORD in the anhydrous and diluted SNEDDS was conducted to achieve the maximum drug loading. The in vitro dissolution of SNEDDS was studied to compare the solubility of the representative formulations with API. The results from the characterization and solubility studies showed that SNEDDS formulations were stable with lower droplet sizes and showed higher ORD solubility. From the dissolution studies, it was found that the developed A7-SNEDDS formulation provided a significantly higher rate of ORD release (98.94 ± 0.68 in 1.0h) compared to API. ORD-loaded SNEDDS formulations could be a potential oral pharmaceutical product with high drug-loading capacity, improved drug dissolution, and enhanced oral bioavailability.

Hybrid poly(lactide-co-glycolide) membranes incorporated with doxycycline-loaded copper-based metal-organic nanosheets as antibacterial platforms.

The rise of antimicrobial resistance necessitates innovative strategies to combat persistent infections. Metal-Organic Frameworks (MOFs) have attracted significant attention as antibiotic carriers due to their high drug loading capacity and structural adaptability. In particular, 2D MOF nanosheets are emerging as a notable alternative to their traditional 3D relatives due to their remarkable advantages in enhanced surface area, flexibility and exposed active region properties. Herein, we synthesized 2D Copper 1,4-benzendicarboxylate (CuBDC) nanosheets and utilized them as a carrier and controlled release system for Doxycycline (Doxy@CuBDC), for the first time. The Doxy@CuBDC nanosheets were subsequently incorporated into poly (DL-lactide-co-glycolide) (PLGA) electrospun membranes (Doxy@CuBDC/PLGA). The resultant bioactive fibrous membranes exhibited double-barrier controlled release properties, extending the Doxy release up to ∼9 days at pH 7.4 and 5.5. Significant inhibitory effects against Staphylococcus aureus and Escherichia coli were observed. The morphological analyses revealed the deformed bacterial cell structures on Doxy@CuBDC/PLGA membranes that indicates potent bactericidal activity. Furthermore, cytotoxicity assays demonstrated the non-toxic nature of the fabricated membranes, underscoring their potential use for biomedical applications. Overall, the hybrid antibacterial PLGA membranes present a promising strategy for combating microbial infections while maintaining biocompatibility and offer a versatile approach for biomedical material design and surface coatings (e.g., wound dressings, implants).&#xD.

Enhancing the Encapsulation Performances of Liposomes for Amphiphilic Copolymers by Computer Simulations.

Liposomes, which encapsulate drugs into an inner aqueous core and demonstrate high drug-loading capacity, have attracted considerable interest in the field of drug delivery. Herein, the encapsulation processes for amphiphilic copolymers within liposomes have been investigated systematically to enhance the encapsulation capacity and optimize the structures using dissipative particle dynamics simulations. The results indicate that the physicochemical properties of lipids, receptors, and amphiphilic copolymers collectively determine the encapsulation behaviors of liposomes. Adjusting the hydrophobic interaction between hydrophobic tails of lipids (receptors) and hydrophobic blocks of copolymers, along with modulating the specific interaction between ligands and the functional head groups of receptors, can lead to various encapsulation capacities. Significantly, a medium hydrophobic interaction strength or a strong specific interaction is conducive to achieving a higher degree of encapsulation for amphiphilic copolymers. Furthermore, varying the key parameters, such as the hydrophobic interaction, the specific interaction, as well as the concentrations of lipids and receptors, can induce seven typical aggregate structures: heterogeneous, fully encapsulated, partially encapsulated, saturated-encapsulated, unsaturated-encapsulated, multilamellar, and column-like structures. The final phase diagrams are also constructed to provide a guideline for designing various structures of liposomes encapsulated with amphiphilic copolymers. These results significantly contribute to the illumination of strategies for the rational construction of the self-assembly system that facilitates the efficient encapsulation of amphiphilic copolymers within the inner aqueous core of liposomes, thereby providing valuable insights into the optimal design of liposome carriers for future biomedical applications.

A Graphene-Based Lipid Modulation Nanoplatform for Synergetic Lipid Starvation/Chemo/Photothermal Therapy of Oral Squamous Cell Carcinoma.

Chemotherapy is one of the most commonly used treatments for oral squamous cell carcinoma (OSCC), but its use is limited by drug resistance and severe systemic toxicity. To eliminate these side effects and improve anti-tumor efficacy, several therapeutic approaches have been developed for use with chemotherapy. In this study, we developed a graphene-based lipid modulation nanoplatform (NSD) that carries SB-204990, a small molecule inhibitor specific for ATP citrate lyase (ACLY), and doxorubicin (DOX), a chemotherapeutic agent, and the trio enables synergistic treatment of OSCC with lipid starvation, chemotherapy, and photothermal therapy. We first determined whether ACLY expression was upregulated in OSCC, and then assessed the growth inhibitory effects of SB-204990 on SCC-15 cells and changes in lipid (acetyl coenzyme A, free fatty acids, and cholesterol) levels. We characterized NSD and then evaluated the stability, photothermal properties, drug loading, and release ability of NSD. Finally, the therapeutic effects of NSD on OSCC were investigated by in vitro and in vivo experiments, and the changes in lipid levels in OSCC tissues after ACLY inhibition were further evaluated. The results showed that ACLY was highly expressed in OSCC, and ACLY inhibition produced reproductive suppression and decreased lipid levels in SCC-15 cells. The NSD nanoplatform possessed good stability, photothermal properties, high drug loading capacity and controlled release. In addition, the triple therapy achieved satisfactory anticancer effects in both in vivo and in vitro assays, and the inhibition rate of tumors was as high as 99.4% in the NSD+Laser treatment group. The changes in tumor cell lipid levels and cell proliferation arrest induced by ACLY inhibition suggest that ACLY may be a promising target for lipid starvation therapy and resistance to chemoresistance, and its inhibitors are expected to become new anticancer drugs. The NSD nanocarrier system enables synergistic treatment with lipid starvation, chemotherapy, and photothermal therapy, which represents an innovative approach to combating tumors.

Targeted delivery of Saikosaponin A and doxorubicin via hyaluronic acid-modified ZIF-8 nanoparticles for TNBC treatment: Inhibiting metastasis and reducing cardiotoxicity

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by the absence of estrogen receptors, progesterone receptors, and HER2 expression, making traditional hormone and targeted therapies ineffective. Chemotherapy remains the primary treatment for TNBC; however, it has failed to adequately address the high rates of recurrence and metastasis, underscoring the urgent need for new therapeutic strategies. This study investigates Saikosaponin A (SSA), a compound extracted from traditional Chinese medicine, for its potential to enhance the efficacy of doxorubicin (DOX) chemotherapy while reducing TNBC metastasis and mitigating DOX-induced cardiotoxicity.We first confirmed SSA's cardioprotective effects against DOX-induced cardiotoxicity, highlighting its potential as an adjunctive therapy for TNBC chemotherapy. Subsequently, through network pharmacology analysis, we identified that SSA may inhibit TNBC progression and metastasis by downregulating integrin β3, a key regulatory factor in tumor development. This was further validated through both in vivo and in vitro experiments. To address the poor bioavailability of SSA, we developed a novel drug delivery system utilizing hyaluronic acid (HA)-modified zeolitic imidazolate framework-8 (ZIF-8) nanoparticles for the co-delivery of SSA and DOX. This nano-drug system exhibited excellent stability and high drug-loading capacity, with loading efficiencies of 40.07 % for SSA and 43.07 % for DOX. After 24 h of nano-drug administration, the DOX concentration in the group using the nano-delivery system was 5.01 times higher than control group, demonstrated enhanced tumor-targeting capability. Furthermore, after 14 days of treatment, the tumor volume was reduced by 80.8 % compared to the control group, indicating significantly improved therapeutic efficacy (all P < 0.05).This study systematically evaluates the potential of this dual drug-loaded nanocarrier in improving TNBC treatment, reducing DOX-induced cardiotoxicity, and inhibiting metastasis, offering a novel therapeutic approach that integrates traditional medicine with advanced nanotechnology.

Enhancing Chemoimmunotherapy for Colorectal Cancer with Paclitaxel and Alantolactone via CD44-Targeted Nanoparticles: A STAT3 Signaling Pathway Modulation Approach

Chemoimmunotherapy has the potential to enhance chemotherapy and modulate the immunosuppressive tumor microenvironment by activating immunogenic cell death (ICD), making it a promising strategy for clinical application. Alantolactone (A) was found to augment the anticancer efficacy of paclitaxel (P) at a molar ratio of 1:0.5 (P:A) through induction of more potent ICD via modulation of STAT3 signaling pathways. Nano drug delivery systems can synergistically combine natural drugs with conventional chemotherapeutic agents, thereby enhancing multi-drug chemoimmunotherapy. To improve tumor targeting ability and bioavailability of hydrophobic drugs, an amphiphilic prodrug conjugate (HA-PTX) was chemically modified with paclitaxel (PTX) and hyaluronic acid (HA) as a backbone. Based on this concept, CD44-targeted nanodrugs (A@HAP NPs) were developed for co-delivery of A and P in colorectal cancer treatment, aiming to achieve synergistic toxicity-based chemo-immunotherapy. The uniform size and high drug loading capacity of A@HAP NPs facilitated their accumulation within tumors through enhanced permeability and retention effect as well as HA-mediated targeting, providing a solid foundation for subsequent synergistic therapy and immunoregulation. In vitro and in vivo studies demonstrated that A@HAP NPs exhibited potent cytotoxicity against tumor cells while also remodeling the immune-suppressive tumor microenvironment by promoting antigen presentation and inducing dendritic cell maturation, thus offering a novel approach for colorectal cancer chemoimmunotherapy.

AuCePt porous hollow cascade nanozymes targeted delivery of disulfiram for alleviating hepatic insulin resistance

As the pathophysiological basis of type 2 diabetes mellitus (T2DM), insulin resistance (IR) is closely related to oxidative stress (OS) and inflammation, while nanozymes have a good therapeutic effect on inflammation and OS by scavenging reactive oxygen species (ROS). Hence, AuCePt porous hollow cascade nanozymes (AuCePt PHNs) are designed by integrating the dominant enzymatic activities of three metallic materials, which exhibit superior superoxide dismutase/catalase-like activities, and high drug loading capacity. In vitro experiments proved that AuCePt PHNs can ultra-efficiently scavenge endogenous and exogenous ROS. Moreover, AuCePt PHNs modified with lactobionic acid (LA) and loaded with disulfiram (DSF), named as AuCePt PHNs-LA@DSF, can significantly improve glucose uptake and glycogen synthesis in IR hepatocytes by regulating the insulin signaling pathways (IRS-1/AKT) and gluconeogenesis signaling pathways (FOXO-1/PEPCK). Intravenous administration of AuCePt PHNs-LA@DSF not only showed high liver targeting efficiency, but also reduced body weight and blood glucose and improved IR and lipid accumulation in high-fat diet-induced obese mice and diabetic ob/ob mice. This research elucidates the intrinsic activity of AuCePt PHNs for cascade scavenging of ROS, and reveals the potential effect of AuCePt PHNs-LA@DSF in T2DM treatment.Graphical abstract

Silk fibroin microspheres with photothermal nanocarrier encapsulation for anticancer drug delivery

Controlled drug release systems are pivotal in optimizing therapeutic outcomes and mitigating side effects in treatment protocols. While traditional delivery vectors such as liposomes, micro/nanoparticles, and microspheres are effective, they often struggle with consistency in drug release rates. This study addresses these issues by integrating stimuli-responsive elements specifically magnetic, thermal, and pH-responsive components into drug delivery systems for precise control. Central to our approach is the use of silk fibroin (SF), chosen for its superior biocompatibility and tunable degradation kinetics. We developed uniform carrier microspheres (CMs) by embedding polydopamine nanoparticles (PDA NPs) into SF microspheres using a custom-designed microfluidic platform. The development process and the application of this platform are detailed, highlighting the precision in control achievable. These CMs showcased enhanced photothermal effects, with the thermal response finely adjustable by altering the PDA NPs concentration, achieving a notable temperature increase of 24.5°C at 7.4 wt% concentration. High drug loading capacity (7.5%) and encapsulation efficiency (91.6%) were achieved, along with a pH-responsive release profile under near-infrared irradiation, paving the way for targeted anticancer drug delivery systems using the model drug doxorubicin hydrochloride. These findings underscore the potential of the developed CMs for external topical application, offering promising prospects for targeted cancer therapy utilizing drug-loaded microspheres.

Synthesis of Carboxylate-Dialdehyde Cellulose to Use as a Component in Composite Thin Films for an Antibacterial Material in Wound Dressing.

Wound infections can lead to life-threatening infection and death. Antibacterial materials from biopolymers in the form of films are a promising strategy for wound dressings. Carboxylate-dialdehyde cellulose (CDAC) is a proper candidate for use as an antibacterial material due to its biocompatibility, nontoxicity, and antibacterial property. Additionally, CDAC can be synthesized from cellulose through environmentally friendly and nontoxic methods. Thus, this study aims to synthesize CDAC from microcrystalline cellulose (MCC) PH102 and use it in composite films for an antibacterial application. The CDAC was synthesized using Fe2+/H2O2, followed by NaIO4 oxidation. The obtained CDAC was characterized in terms of carboxylate and aldehyde content as well as FTIR and XRD spectra. The CDAC was mixed with HPMC in different ratios to prepare films. To determine the optimal formulation for clindamycin HCl loading, the films were evaluated for morphology, mechanical properties, and swelling ratio. Finally, the films containing clindamycin HCl were evaluated for drug loading content, in vitro drug release, and antibacterial activity. This study found that CDAC contained 2.1 ± 0.2 carboxylate and 4.15 ± 0.2 mmol/g of aldehyde content. The FTIR spectra confirmed the successful synthesis. X-ray diffractograms indicated that CDAC was less crystalline than MCC. The film, consisting of CDAC and HPMC E50 in the ratio of 2:1 (D2H1), was identified as the most suitable for clindamycin HCl loading due to its superior appearance, mechanical strength, and swelling properties compared to other formulations. D2H1 exhibited a high drug loading capacity (91.49 ± 5.48%) and demonstrated faster drug release than the film composed only of HPMC because of the higher swelling ratio and lower mechanical strength. This formulation was effective against Staphylococcus aureus (MSSA), S. aureus (MRSA), and Pseudomonas aeruginosa. Furthermore, the D2H1 film containing clindamycin HCl showed a larger inhibition zone against these bacteria, likely due to a synergistic effect. This study found that CDAC has the potential to be applied as an antibacterial material for wound dressing.

Green synthesis of anethole-loaded zinc oxide nanoparticles enhances antibacterial strategies against pathogenic bacteria.

The threat of antibiotic resistance is escalating, diminishing the effectiveness of numerous antibiotics due to the rapid development of resistant bacteria. In response, the use of green-synthesized nanoparticle, alone or combined with antimicrobial agents, appears promising. This study explores the effectiveness of zinc oxide nanoparticles (ZnONPs) synthesized using Loranthus cordifolius leaf extracts and subsequently coated with anethole. The fabrication of these nanoparticles was confirmed via UV-Vis, FTIR and TEM analyses, ensuring the nanoparticles were produced as intended. Utilizing a nanoprecipitation process that excludes evaporation and drying, a high drug loading capacity of 16.59% was accomplished. The encapsulation efficiency for anethole was recorded at 88.23 ± 4.98%. Antibacterial efficacy was assessed by com paring the green-synthesized ZnONPs (average size: 14.47nm), anethole-loaded ZnONPs (average size: 14,75nm), and commercially sourced ZnONPs. The ZnONPs with anethole demonstrated superior inhibition against all tested bacterial strains, including Gram-negative species like Pseudomonas aeruginosa and Escherichia coli, and Gram-positive species like Bacillus subtilis and Staphylococcus aureus, outperforming the commercially available ZnONPs. Additionally, anethole-coated ZnONPs showed the greatest inhibition of Gyr-B activity (IC50 = 0.78 ± 0.2M), better than both green-synthesized and commercially available ZnONPs. These findings emphasize the enhanced antimicrobial properties of ZnONPs, particularly when combined with green synthesis and anethole loading, highlighting their potential in various biomedical applications.

Carrier-Free Biomimetic Organic Nanoparticles with Super-High Drug Loading for Targeted NIR-II Excitable Triple-Modal Bioimaging and Phototheranostics.

Multimodal near-infrared II (NIR-II) theranostics combined with nanotechnology have emerged as promising treatments for cancer due to their noninvasive and high spatiotemporal nature. Traditional NIR-II theranostics typically comprise useless and massive inert carriers, resulting in low drug loading capacity, reduced therapeutic effects, and potential biotoxicity. To overcome these limitations, this work reports carrier-free NIR-II theranostics simultaneously with high drug loading capacity and multimodal NIR-II imaging capabilities for cancer phototheranostics in the NIR-II window. Carrier-free BTA nanoparticles (NPs) are prepared by self-assembling the NIR-II responsive conjugated oligomer BTA without adding coating agents; these NPs exhibited 100% drug loading and high-performance NIR-II theranostic capabilities. Cancer cell membranes are camouflaged on carrier-free BTA NPs to provide homologous targeting ability, enhanced stability, and 77.8% drug loading. Both in vitro and in vivo studies have indicated that biomimetic NPs provide efficient triple-modal guidance for NIR-II fluorescence, photoacoustic, and photothermal imaging and complete tumor elimination via photothermal therapy (PTT). Additionally, theranostics-based treatments with good biosecurity are demonstrated. This study contributes a new strategy for the design of high-drug-loading NIR-II theranostics and further promotes the clinical translation of theranostic agents.

Novel Silybin-Conjugated Chitosan Polymeric Micelles for Improving the Oral Absorption of Doxorubicin Based on the Inhibition of P-gp and CYP3A4.

A drug delivery system based on silybin-conjugated chitosan (CS-SB) polymeric micelles was developed to improve the oral absorption of doxorubicin (DOX). SB was grafted to CS via succinic acid, and CS-SB was identified by 1H NMR and FT-IR. The DOX-loaded micelles were prepared by self-assembly, and the characteristics of micelles, including a small particle size of 167.8 ± 2.3 nm, a high drug loading capacity of 8.59%, and a low critical micelle concentration of 1.3 × 10-5 g/mL, were demonstrated. The micelles showed oral bioavailability of up to 193% versus DOX·HCl. The cytotoxicity test showed the biosafety of CS-SB and the potential of reductive DOX-induced cardiotoxicity. The inhibition of P-gp efflux and CYP3A4 enzyme in CS-SB micelles was confirmed by cellular uptake and enzyme activity inhibition tests. The endocytosis process of micelles was revealed by an endocytosis inhibition test. The findings exhibited the potential of CS-SB micelles in drug delivery.

High loading and sustained-release system of doxorubicin-carbon dots as nanocarriers for cancer therapeutics

Nanocarriers for drugs have been investigated for decades, yet it is still challenging to achieve sustained release from nanomaterials due to drug loading inefficiency and burst release. In this study, we developed novel functional carbon dots (CDs) and investigated the therapeutic efficacy by studying the loading efficiency and release behavior of the anticancer drug doxorubicin (DOX). CDs were successfully synthesized using a one-step pyrolysis method with varying concentrations of citric acid (CA) and thiourea (TU). Functional groups, morphology, particle size, and zeta potential of synthesized CT-CDs and DOX loaded CT-CDs were investigated by UV-visible, Fluorescence, dynamic light scattering, Zeta Potential measurements, FTIR, and transmission electron microscopy. The zeta potential data revealed DOX loading onto CT-CDs by charge difference, i.e. -24.6 ± 0.44 mV (CT-CDs) and 20.57 ± 0.55 mV (DOX-CT-CDs). DOX was loaded on CDs with a loading efficiency of 88.67 ± 0.36%.In vitrodrug release studies confirmed pH-dependent biphasic drug release, with an initial burst effect and sustained release of DOX was found to be 21.42 ± 0.28% (pH 5), 13.30 ± 0.03% (pH 7.4), and 13.95 ± 0.18% (pH 9) even after 144 h at 37 °C. The CT-CDs were non-toxic and biocompatible with L929 Fibroblasts cells. The cytotoxic effect of DOX-CT-CDs showed a concentration-dependent effect after 48 h with Glioblastoma U251 cells. Flow cytometry was used to examine the cellular uptake of CT-CDs and DOX-CT-CDs in L929 and U251 cells. It was observed that the maximum CT-CDs uptake was around 75% at the end of 24 h. This study showed that the synthesized fluorescent CT-CDs demonstrated a high drug loading capacity, pH-dependent sustained release of DOX, and high cellular uptake by mammalian cells. We believe this work provides practical and biocompatible CDs for chemotherapeutic drug delivery that can be applied to other drugs for certain therapeutic aims.

T7 Peptide-modified macrophage membrane-coated nanoplatform for enhanced glioma treatment

The efficient and secure delivery of intravenous chemotherapeutic agents across the blood–brain barrier (BBB) to the precise location of a brain tumor is a crucial element in glioma treatment. Herein, we introduce a biomimetic nanoplatform (T7-M-C/S) comprising a core made up of irinotecan hydrochloride (CPT11) and its bioactive metabolite, 7-Ethyl-10-hydroxycamptothecin (SN38), surrounded by a layer of T7-peptide-modified macrophage membrane. CPT11 spontaneously assembles with SN38 into stable and water-dispersible nanoparticles (C/S), greatly enhancing the water solubility of SN38. The integration of the modified peptide with the inherent proteins expressed by macrophage cells confers the nanoplatform with enhanced bioavailability and robust glioma-targeting abilities, ultimately resulting in superior therapeutic outcomes. These discoveries highlight a drug delivery system characterized by a high drug loading capacity, leveraging the macrophage membrane, and promising significant potential for glioma treatment.

Bacterial Cellulose-Chitosan Composite for Prolonged-Action L-Asparaginase in Treatment of Melanoma Cells.

A significant challenge associated with the therapeutic use of L-ASP for treatment of tumors is its rapid clearance from plasma. Effectiveness of L-ASP is limited by the dose-dependent toxicity. Therefore, new approaches are being developed for L-ASP to improve its therapeutic properties. One of the approaches to improve properties of the enzymes, including L-ASP, is immobilization on various types of biocompatible polymers. Immobilization of enzymes on a carrier could improve stability of the enzyme and change duration of its enzymatic activity. Bacterial cellulose(BC) is a promising carrier for various drugs due to its biocompatibility, non-toxicity, high porosity, and high drug loading capacity. Therefore, this material has high potential for application in biomedicine. Native BC is known to have a number of disadvantages related to structural stability, which has led to consideration of the modified BC as a potential carrier for immobilization of various proteins, including L-ASP. In our study, a BC-chitosan composite in which chitosan is cross-linked with glutaraldehyde was proposed for immobilization of L-ASP. Physicochemical characteristics of the BC-chitosan films were found to be superior to those of native BC films, resulting in increase in the release time of L-ASP invitro from 8 to24h. These films exhibited prolonged toxicity (up to 10h) against the melanoma cell line. The suggested strategy for A-ASP immobilization on the BC-chitosan films could be potentially used for developing therapeutics for treatment of surface types of cancers including melanomas.

Graphene‐Based Nanomaterials are a Potent and Innovative Technology for the Treatment of Cancer: A Review

AbstractCancer is prevailing around the world and so does its mortality rates. Conventionally used therapies have some adverse effects as they are not entirely accurate, leading researchers and investigators to explore new ways and materials. They are constantly looking into ways that can effectively cure this malicious disease and in this effort, they came across new smart materials labeled as nanoparticles (NPs). In between various sorts of nanoparticles, only graphene‐based nanomaterials (GBNMs) shine because of their particular chemical structure and properties. They have high drug loading capacity, can easily target specific tissues, and can be easily functionalized according to the stage and other factors for a patient. Several researches and trials have been executed on animal models to check the potency of these nanoparticles proving them revolutionary in the medical domain, especially for combating cancer. Through this review, we evaluate the experiments conducted by scientists in an effort to devise a platform based on graphene nanoparticles for curing cancer efficiently by using single or multiple therapeutic approaches.

Design and development of DSPE-PEG2000/DPPC disk-like micelles for targeted delivery of icariin phytochemical in pulmonary fibrosis

Icariin (ICA)-loaded DSPE-PEG2000/DPPC disk-like micelles were synthesized utilizing the thin film hydration method to enhance the solubility and delivery of ICA to the lungs. The micellar formulation significantly improved the water solubility of ICA. This was attributed to the high encapsulation efficiency (95 %) and drug loading capacity (12 %) of the DSPE-PEG2000/DPPC micelles. Comprehensive characterization using Fourier-transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD). Particle size analysis through dynamic light scattering (DLS) and transmission electron microscopy (TEM) demonstrated the formation of stable micelles with an average particle size around 10 nm.In vitro aerosolization studies using the next-generation impactor (NGI) revealed that the fine particle fraction was 63.5 ± 4 %, which means that over 60 % of the aerosolized ICA/DSPE-PEG2000/DPPC micelles were capable of reaching and targeting the deep lung alveoli, indicating their potential efficacy for pulmonary delivery. Cytotoxicity assessments via the MTT assay showed IC50 values of ICA-loaded DSPE-PEG2000/DPPC micelles were 117 ± 8 μg/mL, 29 ± 3 μg/mL, and 21 ± 1 μg/mL at 24, 48, and 72 h, respectively, highlighting the time-dependent cytotoxic effects of the ICA-loaded micelles on A549 cells. However, the IC50 values of free ICA were > 500 μg/mL, 252 ± 3 μg/mL, and 109 ± 2 μg/mL, respectively at three different time points. That indicated that ICA-loaded nano micelles enhanced the cytotoxicity of ICA. Furthermore, the cellular uptake of the nano micelles by A549 cells was visualized and confirmed using EVOS fluorescence imaging and flow cytometry techniques. In addition, RAW 264.7 M2 polarization studies indicated ICA loaded DSPE-PEG2000/DPPC micelles have potential for treating pulmonary fibrosis.These findings suggest that DSPE-PEG2000/DPPC micelles significantly enhance the solubility and delivery of ICA, presenting a promising nanocarrier system for targeted pulmonary fibrosis therapy.

PH-sensitive adriamycin hydrochloride and oxaliplatin dual-loaded microspheres synergistically enhance local injections effect of hepatocellular carcinoma

Chemotherapy is the primary palliative treatment for advanced hepatocellular carcinoma (HCC). However, the systemic delivery is associated with the drawbacks including a high risk of adverse effects and a low efficacy. Therefore, local injection therapy may be beneficial. Nevertheless, the existing local drug-carrying microspheres(DOBM)have the characteristics of low loading and abrupt release, can not simultaneously load two drugs, and may cause unnecessary toxicity. In this study, we created the dual-loaded bovine serum albumin (BSA) microspheres (also known as DOBM), which were hollow and contained both oxaliplatin (OXA) and Adriamycin hydrochloride (DOX). In addition, this pH-sensitive drug delivery method exhibited a high drug loading capacity and was promising in breaking through biological barriers, making it a viable option for the treatment of HCC through local implantation. Based on physiochemical evaluation of BSA microspheres, they had a porous structure which was close to the surface. Adriamycin and oxaliplatin were successfully added to the surface of BSA microspheres. According to in vitro experimental results, the growth of human HCC (HCC-LM3 and PLC/PRF/5) cell lines was significantly inhibited by DOBM. Furthermore, in the subcutaneous PLC/PRF/5 HCC model, DOBM played an essential role in tumor development and change in the tumor microenvironment.

Redox-responsive degradation of antimicrobials with programmable drug release for enhanced antibacterial activity

The global crisis of antibiotic resistance has impelled the exigency to develop more effective drug delivery systems for the treatment of bacterial infection. The development of possessing high biocompatibility and targeted delivery of antimicrobials remains a persisting challenge. For programmable release of efficient antimicrobials in infection sites to enhance antibacterial activity, herein, we fabricated diselenide-bridged mesoporous organosilica nanoparticle-supported silver nanoparticles (Ag NPs) with high drug-loading capacity for the co-delivery of tobramycin (TOB) within one drug delivery system (Ag-MON@TOB (Se)). The resultant Ag-MON@TOB (Se) exhibited favorable biocompatibility due to its high stability in the physiological condition. Notably, such Ag-MON@TOB (Se) manifested a programmable structural destabilization to trigger sequential drug release in response to the oxidative stimuli within the bacterial infection microenvironment. In contradistinction to the oxidation-stable disulfide bond moieties within the framework of the nanocarrier (Ag-MON@TOB (S)), the Ag-MON@TOB (Se) with its programmed drug release behavior augmented prominent antibacterial therapy both in vitro and in vivo. This work represents a promising strategy for programmable drug release by harnessing a responsive degradable vehicle to enhance the treatment of bacterial infection.

Metal-organic framework-edaravone nanoparticles for radiotherapy-induced brain injury treatment

Cranial radiotherapy may cause damage to normal brain tissues and induce cognitive dysfunction, so developing an effective strategy to prevent radiotherapy-induced brain injury is essential. Metal-organic frameworks (MOFs) can be used as vectors for the delivery of neuroprotective drugs due to their high drug loading capacity and low toxicity. In this study, we synthesized MIL-53(Cr) nanoparticles, which were used to deliver edaravone, and modified the surface of the nanoparticles with polyethylene glycol and Angiopep-2 (EDA@MIL-53(Cr)–P/A) to improve their oral bioavailability and ability to cross the blood–brain barrier (BBB). We confirmed that MIL-53(Cr)–P/A nanoparticles could achieve the sustained release of edaravone and enhance its ability to cross the BBB. The results of in vitro experiments showed that EDA@MIL-53(Cr)–P/A could exert radioprotective effects on HT22 and BV2 cells. We also demonstrated that EDA@MIL-53(Cr)–P/A could alleviate brain injury and cognitive dysfunction in mice receiving whole-brain irradiation. Mechanistically, EDA@MIL-53(Cr)–P/A alleviated irradiation-induced brain damage by inhibiting oxidative stress, DNA damage, apoptosis and inflammatory reactions. This study provides a new strategy for the protection against radiotherapy-induced brain injury.