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Conventional enhanced permeation and retention (EPR) mediates the effects of many drugs, including the accumulation of nanocarriers at tumor sites, but its efficiency remains low. In this study, this limitation was overcome by developing a dual-targeting delivery system based on hyaluronan (HA, a major ligand of CD44) and tetraiodothyroacetic acid (tetrac, a specific ligand of α v β 3 ), which was exploited to carry docetaxel (DTX) for the synergistic active targeting to tumors. First, a tetrac-HA (TeHA) conjugate was synthesized and grafted onto the surfaces of solid lipid nanoparticles (SLNs) (TeHA-SLNs/DTX), with a high encapsulation efficiency of > 91.6%. The resulting SLNs exhibited an approximately toroid morphology revealed using TEM. The cellular uptake and cytotoxicity of various formulations on CD44/α v β 3 -enriched B16F10 cells were then assessed, and both results confirmed the selective uptake and high cytotoxicity of the TeHA-SLNs/DTX in a TeHA-dependent manner. In vivo imaging and vessel distribution tests revealed the efficiency of synergistic active targeting was higher than that of EPR-mediated passive targeting by the TeHA-SLNs to α v β 3 -expressing tumor blood vessels and CD44-expressing tumor cells via selective targeting. Finally, in both xenograft tumor mice and in situ lung metastasis tumor mice, tumor growth was significantly inhibited by TeHA-SLNs/DTX. Therefore, TeHA-SLNs are an efficient system for the dual-targeted delivery of drugs to treat cancer in vivo . [ABSTRACT FROM AUTHOR]

A co-delivery system that can transport cancer related microRNAs and chemotherapeutics to their distinct targets in the tumors is an attractive strategy to eliminate tumor relapse in lung cancer therapy. In this study, we developed a dual-drug delivery system for an endogenous microRNA (miR-34a) and paclitaxel (PTX) for synergistic cancer therapy. PTX (a meiotic inhibitor) and miR-34a were loaded into cationic solid lipid nanoparticles (miSLNs-34a/PTX) which were used to treat murine B16F10-CD44 + melanoma metastasized to the lungs of mice. This nanoparticle system demonstrated good protection for miR-34a and PTX from degradation in the serum, and had an average size of approximately 220 nm by photon correlation spectroscopy (PCS). In vitro , the parallel activity of PTX and miR-34a show synergistic anticancer efficacy. In vivo , miSLNs-34a/PTX showed passive targetability to the tumor-bearing lung tissues, and was demonstrated to be much more potent in inhibition of B16F10-bearing tumor growth and elimination of cancer cell populations in the lung than single drug-loaded solid lipid nanoparticles. It has been shown that such co-delivery of miR-34a and PTX is promising for enhanced cancer therapy to reduce tumor relapse. [ABSTRACT FROM AUTHOR]

Phytochemical study of Valeriana jatamansi Jones afforded 45 compounds, including twenty-three iridoids (1 – 23), five sesquiterpenes (24 – 28), three steroids (29 – 31) and fourteen lignins (32 – 45). The structures of these compounds were assigned by detailed interpretation of spectroscopic data (1D and 2D NMR, HRESIMS) and comparisons with the published data. This is the first report of isolation of compounds (1 – 6 , 10 , 21 , 25 , 41 , 43 , 44 , 45) from Valerianaceae , compounds (13 , 27 , 39) within the genus Valeriana and compound 30 from V. jatamans. The chemotaxonomic data can support the genus Valeriana being accepted as a member of transitional taxa between the family Valerianaceae and Caprifoliaceae. Image 1 • This is the first report of isolation of compounds (1–6, 10, 21, 25, 41, 43, 44, 45) from Valerianaceae , compounds (13, 27, 39) within the genus Valeriana and compound 30 from V. jatamans. • The chemotaxonomic data can support the genus Valeriana being accepted as a member of transitional taxa between the family Valerianaceae and Caprifoliaceae. All the isolates were evaluated for cytotoxicity effect. [ABSTRACT FROM AUTHOR]

Tissue adhesives are commonly used in surgeries and regenerative engineering for the repair and regeneration of topical and internal wounds on tissues and organs such as skin, heart, blood vessels, and bone. However, achieving rapid crosslinking, strong wet adhesion and cohesion strengths, and minimal cytotoxicity remains a critical roadblock for clinical translation. Herein, in contrast to harsh and cytotoxic oxidants, magnesium oxide (MgO) particles were found to facilitate rapid crosslinking for injectable citrate-based mussel-inspired tissue bioadhesives synthesized by reacting citric acid, PEG-PPG-PEG diol and dopamine (iC-EPE). Our results confirmed the role of MgO particles as both crosslinkers and composite fillers to concurrently enhance bioadhesive cohesion and adhesion. iC-EPE crosslinked by MgO with/without sodium periodate (PI) exhibit enhanced mechanical strengths (1.0 Mpa < tensile strength ≤ 4.5 MPa) compared to that of iC-EPE crosslinked only by PI (~0.75 MPa), high adhesion strength (up to 125 kPa, 8 fold that of fibrin glue (~15 kPa)), tunable degradability (full degradation from <1 week to > 1 month), excellent in vitro and in vivo biocompatibility, encouraging anti-bacterial performance, and favorable wound closure efficacy. Thus, MgO crosslinked bioadhesives possess great potential for a wide range of applications in surgery and regenerative engineering. [ABSTRACT FROM AUTHOR]

Background: Cancer stem cells (CSCs) are highly proliferative and tumorigenic, which contributes to chemotherapy resistance and tumor occurrence. CSCs specific therapy may achieve excellent therapeutic effects, especially to the drug-resistant tumors. Results: In this study, we developed a kind of targeting nanoparticle system based on cationic albumin functionalized with hyaluronic acid (HA) to target the CD44 overexpressed CSCs. All-trans-retinoic acid (ATRA) was encapsulated in the nanoparticles with ultrahigh encapsulation efficiency (EE%) of 93% and loading content of 8.37%. TEM analysis showed the nanoparticles were spherical, uniform-sized and surrounded by a coating layer consists of HA. Four weeks of continuously measurements of size, PDI and EE% revealed the high stability of nanoparticles. Thanks to HA conjugation on the surface, the resultant nanoparticles (HA-eNPs) demonstrated high affinity and specific binding to CD44-enriched B16F10 cells. In vivo imaging revealed that HA-eNPs can targeted accumulate in tumor-bearing lung of mouse. The cytotoxicity tests illustrated that ATRA-laden HA-eNPs possessed better killing ability to B16F10 cells than free drug or normal nanoparticles in the same dose, indicating its good targeting property. Moreover, HA-eNPs/ATRA treatment decreased side population of B16F10 cells significantly in vitro. Finally, tumor growth was significantly inhibited by HA-eNPs/ATRA in lung metastasis tumor mice. Conclusions: These results demonstrate that the HA functionalized albumin nanoparticles is an efficient system for targeted delivery of antitumor drugs to eliminate the CSCs. [ABSTRACT FROM AUTHOR]

Surgical removal remains the predominant treatment strategy for triple-negative breast cancer (TNBC). However, risks that include high locoregional recurrence and remote metastasis threaten patient survival and quality of life after surgery. In this study, a hydrogel based on poly (ethylene glycol) dimethacrylate and sericin methacryloyl was fabricated by photopolymerization to fill the resection cavity and prevent recurrence. The obtained hydrogel exhibited mechanical properties compatible with breast tissue and facilitated postsurgical wound management by promoting tissue regeneration. The DNA methylation inhibitor decitabine (DEC) and poly (lactic- co -glycolic acid)-encapsulated phytochemical gambogic acid (GA) were loaded into the hydrogel. The as-prepared hydrogel promoted fast release of DEC and sustained release of GA, leading to gasdermin E -mediated tumor cell pyroptosis and activating antitumor immune responses. Inducing postsurgical tumor cell pyroptosis inhibited local tumor recurrence and lung metastasis. While the dual-drug-loaded hydrogel system cured less than half of tumor-bearing mice, the cured mice survived for over half a year. These findings indicate that our hydrogel system is an excellent biocompatible platform for postsurgical TNBC therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Nanocarriers entering the body are usually coated by plasma protein, leading to a protein "corona" easily recognized by tissues and cells. Adjusting the composition of protein coronas may be an efficient way to change the properties and behavior of nanoparticles in vivo. In this study, we modified doxorubicin-loaded liposomes (Lip/DOX) with an albumin-binding domain (ABD) to prepare nanoparticles (ABD-Lip/DOX) that can specifically bind to albumin and form albumin-based protein coronas in vivo for targeted tumor therapy. The prepared liposomes were spherical with a particle size of about 100 nm. After incubating the liposomes with rat serum, the albumin content was eight times higher on ABD-Lip than on control liposomes. ABD-Lip significantly inhibited adsorption of IgG and complement activation in rat serum in vitro , while corona-coated ABD-Lip was internalized to a significantly greater extent than corona-coated control liposomes. In addition, ABD-Lip showed longer blood circulation time, higher tumor accumulation and greater antitumor efficacy than control liposomes in mice bearing 4 T1 tumors, while both liposome formulations showed similar biocompatibility. These results confirm that adjusting the component of protein coronas around nanoparticles can improve their therapeutic efficacy. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Imatinib mesylate (IM) is highly effective in the treatment of gastrointestinal stromal tumors (GISTs). However, the most of GISTs patients develop secondary drug resistance after 1–3 years of IM treatment. The aim of this study was to explore the IM-resistance mechanism via the multi-scope combined with plasma concentration of IM, genetic polymorphisms and plasma sensitive metabolites. Methods: This study included a total of 40 GISTs patients who had been regularly treated and not treated with IM. The plasma samples were divided into three experiments, containing therapeutic drug monitoring (TDM), OCT1 genetic polymorphisms and non-targeted metabolomics. According to the data of above three experiments, the IM-resistant cell line, GIST-T1/IMR cells, was constructed for verification the IM-resistance mechanism. Results: The results of non-targeted metabolomics analysis suggested that the sphingophospholipid metabolic pathway including the SPK1/S1P axis was inferred in IM-insensitive patients with GISTs. A GIST cell line (GIST-T1) was immediately induced as an IM resistance cell model (GIST-T1/IMR) and we found that blocking the signal pathway of SPK1/S1P in the GIST-T1/IMR could sensitize treatment of IM and reverse the IM-resistance. Conclusions: Our findings suggest that IM secondary resistance is associated with the elevation of S1P, and blockage the signaling pathway of SPK1/S1P warrants evaluation as a potential therapeutic strategy in IM-resistant GISTs. The design of this study from blood management, group information collection, IM plasma concentration with different elements, identification of sphingolipid metabolism and lastly verification the function of SPK1/S1P in the IM-resistance GISTs cells. [ABSTRACT FROM AUTHOR]

Cancer stem cells (CSCs) drive malignant tumor progression, recurrence, and metastasis with unique characteristics, including self-renewal and resistance to conventional treatments. Conventional differentiation inducers, although promising, have limited cytotoxicity and may inadvertently enhance CSC stemness. To address these challenges, ongoing efforts are dedicated to developing strategies that can effectively combine both cytotoxicity and differentiation-inducing effects. In this study, we introduce oridonin (Ori), a small molecule with dual differentiation-inducing and cytotoxicity properties capable of eliminating tumor CSCs. We isolated CSCs in B16F10 cells using the Hoechst side population method and assessed the differentiation effect of Ori. Ori's differentiation-inducing effect was further evaluated using human acute promyelocytic leukemia. The cytotoxic potential of Ori against MCF-7 and B16F10 cell lines was assessed through various methods. In vivo anti-tumor and anti-CSC efficacy of Ori was investigated using mouse melanoma and CSCs melanoma models. Safety evaluation included zebrafish embryotoxicity and mouse acute toxicity experiments. As a result, Ori effectively dismantles tumorspheres, inhibits proliferation, and reduces the expression of CSC-specific markers. It induces significant differentiation, especially in the case of NB4. Additionally, Ori upregulates TP53 expression, mitigates the hypoxic tumor microenvironment, suppresses stemness, and inhibits PD-L1 expression, prompting a robust anti-cancer immune response. Ori demonstrates pronounced cytotoxicity, inducing notable pro-apoptotic effects on B16F10 and MCF-7 cells, with specific triggering of mitochondrial apoptosis. Importantly, Ori maintains a commendable biosafety record. The dual-action prowess of Ori not only induces the differentiation of CSCs but also dispatches differentiated and residual tumor cells, effectively thwarting the relentless march of tumor progression. Graphic summary illustrates the functions of Oridonin in cancer stem cells and cancer cells. Ori's dual role is to differentiate cancer stem cells and eliminate differentiated cancer cells. [Display omitted] [ABSTRACT FROM AUTHOR]

Highlights: [•] The entrapment efficiency of peptide loaded nanostructured lipid carriers (NLCs) could reach to 95%. [•] The porous nanoparticle-aggregate particles (PNAPs) powders could remain in lungs for a longer time than octreotide acetate (OA) solution and reach a sustained release. [•] The bioavailability was markedly enhanced by pulmonary deliver PNAPs compared with pulmonary deliver OA solutions and subcutaneous inject OA solution. [•] As far as we know, this is the first report on the anti-hepatic ischemia–reperfusion injury (HIRI) effects through intrapulmonary administration. [Copyright &y& Elsevier]

Purpose: To improve gene transducibility mediated by adenovirus (Ad) in cancer cells and further enhance anti-tumor effects by co-delivery. Methods: Calcium-induced phase change method was used to prepare the complex of anionic liposomes and adenovirus (AL/Ad5). Gene expression was qualitatively detected by X-gal staining and quantitatively detected by ELISA. Taking adenovirus-mediated stromal cell-derived factor-1α (Ad5-SDF1α) as therapeutic gene and carmustine (BCNU) as chemotherapeutic agent, a co-delivering system of AL/Ad5-SDF1α/BCNU was prepared and administered to tumor-bearing mice by intratumor injection. Results: Enhanced LacZ gene transduction was obtained in B16 and Lewis lung carcinoma cells in vitro and in vivo. Complexes of AL/Ad5-SDF1α improved SDF1α gene expression and led to accumulation of dendritic cells among the murine B16 melanoma cells in vivo. This co-delivery system of AL/Ad5-SDF1α/BCNU could significantly suppress tumor growth and prolong survival of tumor-bearing mice. Conclusions: Through the co-delivering system, AL/Ad5-SDF1α could synergize with BCNU to improve the antitumor effect. It may be a promising strategy for solid tumor therapy. [ABSTRACT FROM AUTHOR]

Ginsenosides, the main components isolated from Panax ginseng, can play a therapeutic role by inducing tumor cell apoptosis and reducing proliferation, invasion, metastasis; by enhancing immune regulation; and by reversing tumor cell multidrug resistance. However, clinical applications have been limited because of ginsenosides' physical and chemical properties such as low solubility and poor stability, as well as their short half-life, easy elimination, degradation, and other pharmacokinetic properties in vivo. In recent years, developing a ginsenoside delivery system for bifunctional drugs or carriers has attracted much attention from researchers. To create a precise treatment strategy for cancer, a variety of nano delivery systems and preparation technologies based on ginsenosides have been conducted (e.g., polymer nanoparticles [NPs], liposomes, micelles, microemulsions, protein NPs, metals and inorganic NPs, biomimetic NPs). It is desirable to design a targeted delivery system to achieve antitumor efficacy that can not only cross various barriers but also can enhance immune regulation, eventually converting to a clinical application. Therefore, this review focused on the latest research about delivery systems encapsulated or modified with ginsenosides, and unification of medicines and excipients based on ginsenosides for improving drug bioavailability and targeting ability. In addition, challenges and new treatment methods were discussed to support the development of these new tumor therapeutic agents for use in clinical treatment. [ABSTRACT FROM AUTHOR]

Methicillin-resistant Staphylococcus aureus (MRSA) is emerging as a serious pathogenic bacterium in the clinical setting, and antibiotic resistance is spreading faster than the introduction of new agents to kill such bacteria. In our study, Fusarium sp. 152, a marine fungus obtained from the South China Sea, was fermented to screen new anti-MRSA compounds including equisetin (EQ) with a MIC value of 1 µg/mL. Then, EQ was loaded into nanoparticle-based polyvinylpyrrolidone (PVP) electrospinning to facilitate its practical use. After electrospinning, the EQ nanofibers (EQ/NPs nanofiber) were 374.9 nm in diameter, and they showed a good flexibility and foldability. Additionally, the EQ/NPs nanofibers showed a better antibacterial effect both in vitro and in vivo than cefoxitin. Simultaneously, the infectious wounds treated with EQ/NPs nanofiber healed better and faster than those treated with EQ and cefoxitin. These findings strongly demonstrate that PVP-based electrospinning dressings are a candidate delivery carrier for the new anti-MRSA compound EQ for topical therapy. [ABSTRACT FROM AUTHOR]

The anti-infection ability and skin regeneration are important aspects on the progress of wound healing, which needs an ideal wound dressing that not only resists bacteria but also promotes skin regeneration. In this study, zinc oxide/silver/polyvinylpyrrolidone/polycaprolactone (ZnO/Ag/PVP/PCL) nanofibres were prepared through electrospinning. Firstly, zinc oxide nanoparticles (ZnONPs) and silver nanoparticle (AgNPs) were synthesized respectively. Secondly, the two nanoparticles were mixed with polyvinylpyrrolidone (PVP) and polycaprolactone (PCL) to obtain the nanofibres. The results of scanning electron microscopy (SEM) showed that ZnONPs and AgNPs were 40.07 ± 9.70 nm and 37.46 ± 12.02 nm, respectively. After electrospinning, the nanofibres were 368.22 ± 123.96 nm in diameter. Infrared spectroscopy revealed that ZnONPs/AgNPs bimetallic nanomaterials were physically embedded in the nanofibres. The antibacterial effects against Staphylococcus aureus and Escherichia coli of ZnO/Ag/PVP/PCL nanofibres were significantly better than these of the single metal material-loaded nanofibres. More importantly, the combination of ZnO and Ag reduced the cytotoxicity of ZnO/Ag/PVP/PCL bimetallic nanofibres toward fibroblasts. These findings demonstrated that ZnO/Ag/PVP/PCL bimetallic nanofibres should be of greater interest than the single metal nanomaterial-loaded nanofibres in inhibiting growth of bacteria. [ABSTRACT FROM AUTHOR]

[Display omitted] • Cur@PLGA-NPs are a novel AIE formulation capable of providing rich optical properties. • Hydrophobic interaction, electrostatic interaction, and π-π conjugation are responsible for the AIE properties. • The curcumin-based nano-AIE formulation could be successful used to image live cells. To revise the emission of curcumin (Cur) from "off" to "on", poly (D, L-lactide-co-glycolide) acid (PLGA) nanoparticles loaded with Cur were embedded in a polyvinyl alcohol (PVA) emulsifier (named Cur@PLGA-NPs). First, the emission intensities of different nanoformulations, including liposomes, bovine serum albumin (BSA) nanoparticles, and PLGA nanoparticles, were examined to discover the most effective carriers for Cur luminescence. As a result, Cur@PLGA-NPs exhibited the highest fluorescence intensity due to aggregation-induced emission (AIE), with quantum yields of 23.78% in aqueous solution and 21.52% in the solid state. According to X-ray diffraction (XRD) data, Cur@PLGA-NPs existed in the amorphous state, with a size of 217.2 ± 5.2 nm, an encapsulation efficiency (EE) of 69.98%, and a drug loading efficiency (LE) of 1.37%. The intramolecular interactions, which included hydrophobic interactions, electrostatic interactions, π-π interactions and solvatochromic effects, stabilized the chromophore cluster of Cur@PLGA-NPs in terms of nanoparticle formulation. Compared with free Cur, Cur@PLGA-NPs sensitized CT26 cells more efficiently with an IC 50 value of 16.9 μmol/L and an apoptotic rate of 17.20% at 10 μmol/L Cur. Because of the robust fluorescence emission based on AIE, Cur@PLGA-NPs were utilized as a nano-AIE probe for cell bioimaging, and many red fluorescent signals were observed in CT26 cells after treatment. These results suggest that Cur@PLGA-NPs provide a novel amorphous AIE formulation with imaging and bioactive capabilities. [ABSTRACT FROM AUTHOR]

A co-loaded drug delivery system based on ascorbyl palmitate that can transport various functional drugs to their targets within a tumor represents an attractive strategy for increasing the efficiency of anticancer treatment. In this study, we developed a dual drug delivery system to encapsulate ascorbyl palmitate (AP) and paclitaxel (PTX) for synergistic cancer therapy. AP, which is a vitamin C derivative, and PTX were incorporated into solid lipid nanoparticles (AP/PTX-SLNs), which were used to treat murine B16F10 melanoma that had metastasized to the lungs of mice. These nanoparticles were spherical with an average size of 223 nm as measured by transmission electron microscope and dynamic light scattering.In vitrocytotoxicity assays indicated that the AP/PTX-SLNs with an AP/PTX mass ratio of 2/1 provided the optimal synergistic anticancer efficacy.In vivo, AP/PTX-SLNs were revealed to be much more effective in suppressing tumor growth in B16F10-bearing mice and in eliminating cancer cells in the lungs than single drug (AP or PTX)-loaded SLNs via a synergistic effect through reducing the Bcl-2/Bax ratio. Furthermore, no marked side effects were observed during the treatment with the AP/PTX-SLNs, indicating that the co-delivery system with ascorbyl palmitate holds promising clinical potential in cancer therapy. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC), among the most aggressive and prevailing neoplasms, is primarily treated with chemotherapy. Voacamine (VOA), a novel bisindole natural product, possesses a variety of conspicuous pharmacological activities. Within the current research, we evaluated in vitro and in vivo the anticancer efficacy of VOA against CRC and its potential mechanisms. Our results illustrated that VOA concentrationdependently suppressed the proliferation and migration of CT26 and HCT116 cells as correspondingly indicated by IC 50 values of 1.38 ± 0.09 μM and 4.10 ± 0.14 μM. Furthermore, treatment of VOA also suppressed tumor cell colony formation, escalated the late-stage apoptosis rate of tumor cells, and evoked cell cycle of CT26 and HCT116 cells arrest inhibition in G2-M and G0-G1 phases, respectively. Meanwhile, VOA markedly disrupted the mitochondrial membrane potential eliciting mitochondrial dysfunction, decreased ATP production, and intermediated an enhanced accumulation of intracellular reactive oxygen species with a concentration-dependent pattern, accompanied by elevated expression levels of pro-apoptotic related protein Bax, Cyt-C, cleaved caspases 3/8/9 and by diminished Bcl-2, Bid, PRAP and caspases 3/8/9 expression. Further mechanistic studies revealed VOA treatment suppressed the EGFR/PI3K/Akt pathway with the evidence of the decreased phosphorylation proteins of EGFR, PI3K, Akt, and downstream proteins of p-mTOR, p-NF-kB, and p-P70S6. Additionally, molecular dynamics simulations further displayed VOA could enter the EGFR pocket followed by multiple mutual interaction effects. Interestingly, the EGFR activator (NSC228155) could slack the inhibitory capability of VOA on the EGFR/PI3K/Akt pathway as well as VOA-induced impairment of mitochondrial function. Finally, administration of VOA (15, 30 mg/kg every 2 days, i.p., for 16 days) in CT26 syngeneic mice dose-dependently suppressed the neoplastic development without appreciable organ toxicities. Taken together, our study demonstrated that VOA may be a prospective therapeutic agent for the treatment of CRC. [Display omitted] [ABSTRACT FROM AUTHOR]

This study reports on the performance of sodium alginate (SA)/poly(vinyl alcohol) (PVA)/moxifloxacin hydrochloride (MH) nanofibrous membranes (NFM) capable of providing antibacterial agent delivery for wound-dressing applications. The aim of this work was to prepare antibacterial NFM with good permeability properties by employing PVA and SA as carriers. A group of 12% PVA/2% SA solutions blended in various ratios (8:2, 7:3, 6:4, 5:5 and 4:6, v/v) and containing 0.5, 1, 2 or 4 wt% MH were studied for electrospinning into nanoscale fibermats. The optimum ratio found to form smooth fibers with uniform fibrous features was 6:4. The drug release behavior of the electrospun, the antibacterial effects onPseudomonas aeruginosaandStaphylococcus aureusand the animal wound dressing capabilities were also investigated. As much as 80% of the MH was released from the electrospun after 10 h of incubation at 37 °C. In addition, the NFM with 0.5 MH exhibited less activity, whereas those with higher concentrations of MH exhibited greater antibacterial effect. Furthermore, the MH-loaded electrospun accelerated the rate of wound dressing compared to other groups. The results of thein vitroandin vivoexperiments suggest that MH/PVA/SA nanofibers might be an interesting bioactive wound dressing for clinical applications. [ABSTRACT FROM PUBLISHER]

[Display omitted] • Sustained local anesthetics system can improve the satisfaction of patient. • Poloxamer 407 can release drugs sustained but with higher initial burst release. • Ropivacaine loaded injectable liposome-in-gel had low initial burst release. • Ropivacaine loaded gel was useful for local anesthesia without systemic toxicity. Reducing post-surgical pain can promote recovery of mobility, improve patient satisfaction, and reduce the risk of chronic pain syndrome. When managing post-surgical pain, single-injection local anesthesia is more convenient and involves lower risk to the patient than multi-injection regimes, but the effects are not long-lasting. Here we developed a system that can prolong local anesthesia after a single injection. In this system, ropivacaine (Ro) is encapsulated into liposomes, which are then loaded into Poloxamer 407-based thermosensitive hydrogels. The Ro-loaded liposome-in-gel system (Ro-Lip-Gel) is in a sol state before injection, and immediately after subcutaneous injection, it forms a gel in situ. We show through in vitro release and in vivo pharmacokinetics studies that this gel acts as a drug release depot. In rats, the initial burst release of Ro was smaller from Ro-Lip-Gel than from Ro solution or Ro-Gel, and Ro-Lip-Gel caused nerve blockade lasting four times longer than Ro solution. Ro-Lip-Gel degraded in vivo and showed good biocompatibility. Our results suggest that a liposome-in-gel system can show small initial burst release, long-term nerve blockade and good biocompatibility in vitro and in vivo. Therefore, such a system may be useful for sustained local anesthesia without systemic toxicity. [ABSTRACT FROM AUTHOR]