scholarly journals Repeatable and adjustable on-demand sciatic nerve block with phototriggerable liposomes

2015 ◽  
Vol 112 (51) ◽  
pp. 15719-15724 ◽  
Author(s):  
Alina Y. Rwei ◽  
Jung-Jae Lee ◽  
Changyou Zhan ◽  
Qian Liu ◽  
Meryem T. Ok ◽  
...  
Keyword(s):  
Cell Culture ◽  
Sciatic Nerve ◽  
Local Anesthesia ◽  
Nerve Block ◽  
Near Infrared ◽  
Tissue Reaction ◽  
On Demand ◽  
Nir Light

Pain management would be greatly enhanced by a formulation that would provide local anesthesia at the time desired by patients and with the desired intensity and duration. To this end, we have developed near-infrared (NIR) light-triggered liposomes to provide on-demand adjustable local anesthesia. The liposomes contained tetrodotoxin (TTX), which has ultrapotent local anesthetic properties. They were made photo-labile by encapsulation of a NIR-triggerable photosensitizer; irradiation at 730 nm led to peroxidation of liposomal lipids, allowing drug release. In vitro, 5.6% of TTX was released upon NIR irradiation, which could be repeated a second time. The formulations were not cytotoxic in cell culture. In vivo, injection of liposomes containing TTX and the photosensitizer caused an initial nerve block lasting 13.5 ± 3.1 h. Additional periods of nerve block could be induced by irradiation at 730 nm. The timing, intensity, and duration of nerve blockade could be controlled by adjusting the timing, irradiance, and duration of irradiation. Tissue reaction to this formulation and the associated irradiation was benign.

H2O2/near-infrared light-responsive nanotheronostics for MRI-guided synergistic chemo/photothermal cancer therapy

Nanomedicine ◽  
2019 ◽  
Vol 14 (16) ◽  
pp. 2189-2207
Author(s):  
Yiming Yu ◽  
Li Zhang ◽  
Miao Wang ◽  
Zhe Yang ◽  
Leping Lin ◽  
...  
Keyword(s):  
Near Infrared ◽  
Tumor Model ◽  
Mri Contrast Agent ◽  
Infrared Light ◽  
Antitumor Effects ◽  
Mri Contrast ◽  
Nir Light ◽  
Nir Laser

Aim: To develop a H2O2/near-infrared (NIR) laser light-responsive nanoplatform (manganese-doped Prussian blue@polypyrrole [MnPB@PPy]) for synergistic chemo/photothermal cancer theranostics. Materials & methods: Doxorubicin (DOX) was loaded onto the surface of polypyrrole shells. The in vitro and in vivo MRI performance and anticancer effects of these nanoparticles (NPs) were evaluated. Results: The MnPB@PPy NPs could not only generate heat under NIR laser irradiation for cancer photothermal therapy but also act as an excellent MRI contrast agent. The loaded DOX could be triggered to release by both NIR light and H2O2 to enhance synergistic therapeutic efficacy. The antitumor effects were confirmed by in vitro cellular cytotoxicity assays and in vivo treatment in a xenograft tumor model. Conclusion: The designed H2O2/NIR light-responsive MnPB@PPy-DOX NPs hold great potential for future biomedical applications.

scholarly journals Ultralong Peripheral Nerve Block by Lidocaine:Prilocaine 1:1 Mixture in a Lipid Depot Formulation

2006 ◽  
Vol 104 (1) ◽  
pp. 110-121 ◽  
Author(s):  
Lars Söderberg ◽  
Henrik Dyhre ◽  
Bodil Roth ◽  
Sven Björkman
Keyword(s):  
Sciatic Nerve ◽  
Nerve Block ◽  
Local Anesthetic ◽  
In Vitro Release ◽  
Sciatic Nerve Block ◽  
Depot Formulation ◽  
Duration Of Action ◽  
Depot Preparations

Background The aim of this study was to develop stable and easily injectable lipid depot preparations of local anesthetics in which the drug concentration can be varied according to desired duration of action. Methods The formulations contained a 2.0, 5.0, 10, 20, 40, 60, 80, or 100% eutectic mixture of lidocaine and prilocaine base in medium-chain triglyceride. Duration of sciatic nerve block and local neurotoxicity was investigated in rats with 2.0% lidocaine:prilocaine HCl solution and 99.5% ethanol as controls. The rate of release of local anesthetic from the site of administration and the possibility to predict in vivo depot characteristics from in vitro release data were investigated for the 20 and 60% formulations. Results The duration of sensory sciatic block was prolonged 3 times with the 20% formulation and approximately 180 times with the 60% formulation, in comparison with the 2% aqueous solution. With the 80 and 100% formulations, all animals still showed nerve block after 2 weeks. The in vivo release of local anesthetic could be approximately predicted from in vitro data for the 20% but not for the 60% formulation. The formulations of 60% or greater and ethanol showed neurotoxic effects. Conclusions The pharmaceutical properties of these formulations compare favorably with those of other depot preparations. The high-percentage ones showed the longest duration of action yet reported for sciatic nerve block in rats. The possibility of using a high-concentration local anesthetic depot formulation as an alternative to ethanol or phenol for long-term nerve blocks in chronic pain merits further investigation.

Intra-articular Administrated Hydrogels of Hyaluronic Acid Hybridized with Triptolide/Gold Nanoparticles for Targeted Delivery to Rheumatoid Arthritis Combined with Photothermal-chemo Therapy

2021 ◽  
Author(s):  
Chenxi Li ◽  
Rui Liu ◽  
Yurong Song ◽  
Dongjie Zhu ◽  
Liuchunyang Yu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Hyaluronic Acid ◽  
Targeted Delivery ◽  
Near Infrared ◽  
Invasion And Migration ◽  
Nir Light ◽  
Hybrid Hydrogels ◽  
And Migration

Abstract Triptolide (TP) as a disease-modifying anti-rheumatic drug (DMARD) is effective on the treatment of rheumatoid arthritis (RA). To alleviate the toxicity and elevate therapeutic specificity, hyaluronic acid (HA) hydrogels load RGD-attached gold nanoshell containing TP are synthesized, which can be used for targeted photothermal-chemo therapy, and imaging of RA in vivo. The hydrogels system composed of thiol and tyramine modified HA conjugates has been applied artificial tissue models of cartilage for studying drug delivery and release properties. After the degradation of HA chains, heat together with drugs can be delivered to the inflammatory joints simultaneously due to the near-infrared resonance (NIR) irradiation of Au nanoshell. RA is a chronic inflamed disease, which is characterized by synovial inflammation of multiple joints, and can be penetrated with NIR light. These intra-articular administrated hybrid hydrogels combined with NIR irradiation can improve clinical arthritic conditions and inflamed joints in collagen-induced arthritis (CIA) mice, which just need a smaller dosage of TP with non-toxicity. Additionally, the TP-Au/HA hybrid hydrogels treatment reduced the invasion and migration of RA fibroblast-like synoviocytes (RA-FLSs) in vitro significantly, through reducing the phosphorylation of mTOR and p70S6K, its substrates, and confirmed that the mTOR pathway was inhibited.

scholarly journals Deep-Tissue Photothermal Therapy Using Laser Illumination at NIR-IIa Window

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Xunzhi Wu ◽  
Yongkuan Suo ◽  
Hui Shi ◽  
Ruiqi Liu ◽  
Fengxia Wu ◽  
...  
Keyword(s):  
Photothermal Therapy ◽  
Near Infrared ◽  
Laser Excitation ◽  
Tumor Treatment ◽  
Deep Tissue ◽  
Laser Illumination ◽  
Nir Light ◽  
Cell Ablation

Abstract Photothermal therapy (PTT) using near-infrared (NIR) light for tumor treatment has triggered extensive attentions because of its advantages of noninvasion and convenience. The current research on PTT usually uses lasers in the first NIR window (NIR-I; 700–900 nm) as irradiation source. However, the second NIR window (NIR-II; 1000–1700 nm) especially NIR-IIa window (1300–1400 nm) is considered much more promising in diagnosis and treatment as its superiority in penetration depth and maximum permissible exposure over NIR-I window. Hereby, we propose the use of laser excitation at 1275 nm, which is approved by Food and Drug Administration for physical therapy, as an attractive technique for PTT to balance of tissue absorption and scattering with water absorption. Specifically, CuS-PEG nanoparticles with similar absorption values at 1275 and 808 nm, a conventional NIR-I window for PTT, were synthesized as PTT agents and a comparison platform, to explore the potential of 1275 and 808 nm lasers for PTT, especially in deep-tissue settings. The results showed that 1275 nm laser was practicable in PTT. It exhibited much more desirable outcomes in cell ablation in vitro and deep-tissue antitumor capabilities in vivo compared to that of 808 nm laser. NIR-IIa laser illumination is superior to NIR-I laser for deep-tissue PTT, and shows high potential to improve the PTT outcome.

Potency of Bupivacaine Stereoisomers Tested  In Vitro and  In Vivo

2000 ◽  
Vol 93 (3) ◽  
pp. 744-755 ◽  
Author(s):  
Marina Vladimirov ◽  
Carla Nau ◽  
Wai Man Mok ◽  
Gary Strichartz
Keyword(s):  
Sciatic Nerve ◽  
Nerve Block ◽  
Local Anesthetics ◽  
Neuroendocrine Cells ◽  
Primary Role ◽  
Na Channels ◽  
Rat Sciatic Nerve ◽  
Na Currents

Background Chiral local anesthetics, such as ropivacaine and levobupivacaine, have the potential advantage over racemic mixtures in showing reduced toxic side effects. However, these S-(levo, or "-")isomers also have reportedly lower potency than their optical antipode, possibly resulting in no advantage in therapeutic index. Potency for local anesthetics inhibiting Na+ channels or action potentials depends on the pattern of membrane potential and so also does the stereopotency ratio. Here the authors have quantitated the stereopotencies of R-, S-, and racemic bupivacaine, comparing several in vitro assays of neuronal Na+ channels with those from in vivo functional nerve block, to establish relative potencies and to understand better the role of different modes of channel inhibition in overall functional anesthesia. Methods The binding of bupivacaine to Na+ channels was assessed indirectly by its antagonism of [3H]-batrachotoxin binding to rat brain synaptosomes. Inhibition of Na+ currents by bupivacaine was directly assayed in voltage-clamped GH-3 neuroendocrine cells. Neurobehavioral functions were disrupted by bupivacaine percutaneously injected (0.1 ml; 0.0625-1.0%) at the rat sciatic nerve and semiquantitatively assayed. Concentration-dependent actions of R-, S-, and racemic bupivacaine were compared for their magnitude and duration of action. Results Competitive batrachotoxin displacement has a stereopotency ratio of R:S = 3:1. Inhibition of Na+ currents with different prepulse potentials shows that S > R potency when the membrane is hyperpolarized, and R > S potency when it is depolarized from normal resting values. Functional deficits assayed in vivo usually demonstrate no consistent enantioselectivity and only a modest stereopotency (R:S = 1.2-1.3) for peak analgesia achieved at the lowest doses. Other functions display no significant stereopotency in either the degree, the duration, or their product (area under the curve) at any dose. Conclusion Although the in vitro actions of bupivacaine showed stereoselectivity ratios of 1.3-3:1 (R:S), in vivo nerve block at clinically used concentrations showed much smaller ratios for peak effect and no significant enantioselectivity for duration. A primary role for the blockade of resting rather than open or inactivated Na+ channels may explain the modest stereoselectivity in vivo, although stereoselective factors controlling local disposition cannot be ruled out. Levo-(S-)bupivacaine is effectively equipotent to R- or racemic bupivacaine in vivo for rat sciatic nerve block.

scholarly journals Spatiotemporal depletion of tumor-associated immune checkpoint PD-L1 with near-infrared photoimmunotherapy promotes antitumor immunity

2021 ◽  
Vol 9 (11) ◽  
pp. e003036
Author(s):  
Shunichi Taki ◽  
Kohei Matsuoka ◽  
Yuko Nishinaga ◽  
Kazuomi Takahashi ◽  
Hirotoshi Yasui ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Immune Checkpoint ◽  
Antitumor Immunity ◽  
Near Infrared ◽  
Specific Antigen ◽  
Cancer Therapeutics ◽  
Antitumor Effects ◽  
Nir Light

BackgroundNear-infrared photoimmunotherapy (NIR-PIT) is a new modality for treating cancer, which uses antibody-photoabsorber (IRDye700DX) conjugates that specifically bind to target tumor cells. This conjugate is then photoactivated by NIR light, inducing rapid necrotic cell death. NIR-PIT needs a highly expressed targeting antigen on the cells because of its reliance on antibodies. However, using antibodies limits this useful technology to only those patients whose tumors express high levels of a specific antigen. Thus, to propose an alternative strategy, we modified this phototechnology to augment the anticancer immune system by targeting the almost low-expressed immune checkpoint molecules on tumor cells.MethodsWe used programmed death-ligand 1 (PD-L1), an immune checkpoint molecule, as the target for NIR-PIT. Although the expression of PD-L1 on tumor cells is usually low, PD-L1 is almost expressed on tumor cells. Intratumoral depletion with PD-L1-targeted NIR-PIT was tested in mouse syngeneic tumor models.ResultsAlthough PD-L1-targeted NIR-PIT showed limited effect on tumor cells in vitro, the therapy induced sufficient antitumor effects in vivo, which were thought to be mediated by the ‘photoimmuno’ effect and antitumor immunity augmentation. Moreover, PD-L1-targeted NIR-PIT induced antitumor effect on non-NIR light-irradiated tumors.ConclusionsLocal PD-L1-targeted NIR-PIT enhanced the antitumor immune reaction through a direct photonecrotic effect, thereby providing an alternative approach to targeted cancer immunotherapy and expanding the scope of cancer therapeutics.

scholarly journals Near-infrared upconversion–activated CRISPR-Cas9 system: A remote-controlled gene editing platform

2019 ◽  
Vol 5 (4) ◽  
pp. eaav7199 ◽  
Author(s):  
Yongchun Pan ◽  
Jingjing Yang ◽  
Xiaowei Luan ◽  
Xinli Liu ◽  
Xueqing Li ◽  
...  
Keyword(s):  
Gene Editing ◽  
Near Infrared ◽  
Cancer Therapeutics ◽  
Guide Rna ◽  
System A ◽  
Nir Light ◽  
Targeted Gene Editing ◽  
Daunting Challenge

As an RNA-guided nuclease, CRISPR-Cas9 offers facile and promising solutions to mediate genome modification with respect to versatility and high precision. However, spatiotemporal manipulation of CRISPR-Cas9 delivery remains a daunting challenge for robust effectuation of gene editing both in vitro and in vivo. Here, we designed a near-infrared (NIR) light–responsive nanocarrier of CRISPR-Cas9 for cancer therapeutics based on upconversion nanoparticles (UCNPs). The UCNPs served as “nanotransducers” that can convert NIR light (980 nm) into local ultraviolet light for the cleavage of photosensitive molecules, thereby resulting in on-demand release of CRISPR-Cas9. In addition, by preparing a single guide RNA targeting a tumor gene (polo-like kinase-1), our strategies have successfully inhibited the proliferation of tumor cell via NIR light–activated gene editing both in vitro and in vivo. Overall, this exogenously controlled method presents enormous potential for targeted gene editing in deep tissues and treatment of a myriad of diseases.

CuS–Pt(iv)–PEG–FA nanoparticles for targeted photothermal and chemotherapy

2016 ◽  
Vol 4 (35) ◽  
pp. 5938-5946 ◽  
Author(s):  
Huiting Bi ◽  
Yunlu Dai ◽  
Jiating Xu ◽  
Ruichan Lv ◽  
Fei He ◽  
...  
Keyword(s):  
Photothermal Therapy ◽  
Near Infrared ◽  
Drug Induced ◽  
Nir Light

CuS–Pt(iv) nanoparticles exhibited high in vitro and in vivo anti-tumor efficiency, which was caused by the integrated Pt drug-induced chemotherapy and CuS nanoparticle-mediated photothermal therapy (PTT) upon irradiation with near infrared (NIR) light.

scholarly journals Lido-OH, a Hydroxyl Derivative of Lidocaine, Produced a Similar Local Anesthesia Profile as Lidocaine With Reduced Systemic Toxicities

2021 ◽  
Vol 12 ◽  
Author(s):  
Qinqin Yin ◽  
Weiyi Zhang ◽  
Bowen Ke ◽  
Jin Liu ◽  
Wensheng Zhang
Keyword(s):  
Sciatic Nerve ◽  
Local Anesthesia ◽  
Nerve Block ◽  
Therapeutic Index ◽  
Negative Control ◽  
Sciatic Nerve Block ◽  
Dose Effect ◽  
Effective Doses ◽  
Block Models

Background: lidocaine is one of the most commonly used local anesthetics for the treatment of pain and arrhythmia. However, it could cause systemic toxicities when plasma concentration is raised. To reduce lidocaine’s toxicity, we designed a hydroxyl derivative of lidocaine (lido-OH), and its local anesthesia effects and systemic toxicity in vivo were quantitively investigated.Method: the effectiveness for lido-OH was studied using mouse tail nerve block, rat dorsal subcutaneous infiltration, and rat sciatic nerve block models. The systemic toxicities for lido-OH were evaluated with altered state of consciousness (ASC), arrhythmia, and death in mice. Lidocaine and saline were used as positive and negative control, respectively. The dose-effect relationships were analyzed.Results: the half effective-concentration for lido-OH were 2.1 mg/ml with 95% confident interval (CI95) 1.6–3.1 (lidocaine: 3.1 mg/ml with CI95 2.6–4.3) in tail nerve block, 8.2 mg/ml with CI95 8.0–9.4 (lidocaine: 6.9 mg/ml, CI95 6.8–7.1) in sciatic nerve block, and 5.9 mg/ml with CI95 5.8–6.0 (lidocaine: 3.1 mg/ml, CI95 2.4–4.0) in dorsal subcutaneous anesthesia, respectively. The magnitude and duration of lido-OH were similar with lidocaine. The half effective doses (ED50) of lido-OH for ACS was 45.4 mg/kg with CI95 41.6–48.3 (lidocaine: 3.1 mg/kg, CI95 1.9–2.9), for arrhythmia was 16.0 mg/kg with CI95 15.4–16.8 (lidocaine: 3.0 mg/kg, CI95 2.7–3.3), and for death was 99.4 mg/kg with CI95 75.7–124.1 (lidocaine: 23.1 mg/kg, CI95 22.8–23.4). The therapeutic index for lido-OH and lidocaine were 35.5 and 5.6, respectively.Conclusion: compared with lidocaine, lido-OH produced local anesthesia at similar potency and efficacy, but with significantly reduced systemic toxicities.

scholarly journals Ultrasound-triggered on Demand Lidocaine Release Relieves Postoperative Pain

2021 ◽  
Author(s):  
Xiaohong Chen ◽  
Jianfeng Zhang ◽  
Yan Yu ◽  
Haoran Wang ◽  
Genshan Ma ◽  
...  
Keyword(s):  
Postoperative Pain ◽  
Three Dimensional ◽  
Systemic Effect ◽  
Tissue Reaction ◽  
Control Group ◽  
3D Scaffold ◽  
Nerve Blocks ◽  
On Demand

Abstract BackgroundSafe and noninvasive on-demand relief is a crucial and effective treatment for postoperative pain because it considers variable timing and intensity of anesthetics. Ultrasound modulation is a promising technique for this treatment because it allows convenient timed and noninvasive controlled drug release.MethodsWe created an ultrasound-triggered lidocaine (Lido) release platform using an amino acid hydrogel functioning as three dimensional (3D) scaffold material (Lido-PPIX@ER hydrogel). Optimal preparation conditions and ultrasound-triggered parameters were evaluated. In the postoperative pain SD rat model, the Lido-PPIX@ER hydrogel or free lidocaine was administered by subcutaneous injection immediately after making the paw incision. Mechanical hypersensitivity was assessed using calibrated von Frey filaments after an individualized (highly variable) ultrasound-triggered process. The safety of the treatment was also evaluated.ResultsThe Lido-PPIX@ER hydrogel allows control of the timing, intensity and duration of lidocaine (Lido) to relieve postoperative pain. The hydrogel releases Lido due to the elevated reactive oxygen species (ROS) levels generated by PPIX under ultrasound triggering. The optimal ultrasound parameter (0.3 W/cm2, 30 s) was chosen for in vitro and in vivo studies. The Lido-PPIX@ER hydrogel (with lidocaine, 5.6 mg/mL) under individualized ultrasound triggering (every 2 h in the first 12 h, every 4 h for the next 36 h, and then every 6 h until 72 h postsurgery) released lidocaine and provided effective analgesia for more than 72 h. Additionally, the withdrawal threshold was higher than that in the control group at all time points measured. The hydrogel showed repeatable and adjustable ultrasound-triggered nerve blocks in vivo, the duration of which depended on the extent and intensity of insonation. On histopathology, no systemic effect or tissue reaction was observed in the ultrasound-triggered Lido-PPIX@ER hydrogel-treated group.ConclusionsThe Lido-PPIX@ER hydrogel with individualized (highly variable) ultrasound triggering is a convenient and effective method that offers timed and spatiotemporally controlled Lido release to manage postoperative pain.

Sign in / Sign up

Export Citation Format

Share Document