A food-grade and senescent cell-targeted fisetin delivery system based on whey protein isolate-galactooligosaccharides Maillard conjugate

Cellular senescence is the results of aging and age-related diseases,and the development of anti-aging methods may improve health and extend longevity.The natural flavonol fisetin has been shown to antagonize senescence in vitro and increases longevity in vivo,but has poor water solubility and limited bioavailability.In this study,a food-grade and senescent cell-targeted delivery system for fisetin was developed based on whey protein isolate-galactooligosaccharides(WPI-GOS)Maillard conjugate,which could recognize senescence associatedβ-galactosidase in senescent cells.The fisetin nanoparticles possessed a high encapsulation efficiency,excellent dispersibility in water,good storage stability and well biocompatibility.Moreover,they could effectively accumulate and retain in senescent cells with excellent senescent cell-targeting efficacy,and inhibit the oxidative stress-induced cellular senescence in vitro.Thus,this novel nanoparticle system based on WPI-GOS Maillard conjugate showed promise to deliver hydrophobic bioactive ingredients like fisetin to senescent cells to improve their bioavailability and anti-senescence effect.

Recent advances in zwitterionic nanoscale drug delivery systems to overcome biological barriers

Nanoscale drug delivery systems(nDDS)have been employed widely in enhancing the therapeutic efficacy of drugs against diseases with reduced side effects.Although several nDDS have been successfully approved for clinical use up to now,biological barriers between the administration site and the target site hinder the wider clinical adoption of nDDS in disease treatment.Polyethylene glycol(PEG)-modification(or PEGylation)has been regarded as the gold standard for stabilising nDDS in complex biological environment.However,the accelerated blood clearance(ABC)of PEGylated nDDS after repeated injections becomes great challenges for their clinical applications.Zwitterionic polymer,a novel family of antifouling materials,have evolved as an alternative to PEG due to their super-hydrophilicity and biocompatibility.Zwitterionic nDDS could avoid the generation of ABC phenomenon and exhibit longer blood circulation time than the PEGylated analogues.More impressively,zwitterionic nDDS have recently been shown to overcome multiple biological barriers such as nonspecific organ distribution,pressure gradients,impermeable cell membranes and lysosomal degradation without the need of any complex chemical modifications.The realization of overcoming multiple biological barriers by zwitterionic nDDS may simplify the current overly complex design of nDDS,which could facilitate their better clinical translation.Herein,we summarise the recent progress of zwitterionic nDDS at overcoming various biological barriers and analyse their underlyingmechanisms.Finally,prospects and challenges are introduced to guide the rational design of zwitterionic nDDS for disease treatment.

A Study on the Multi-Compartment Linear Circulation Pharmacokinetic Model for the Targeting Drug Delivery System

By analyzing the observed phenomena and the data collected in the study, a multi-compartment linear circulation model for targeting drug delivery system was developed and the function formulas of the drug concentration-time in blood and target organ by computing were figured out. The drug concentration-time curve for target organ can be plotted with reference to the data of drug concentration in blood according to the model. The pharmacokinetic parameters of the drug in target organ could also be obtained. The practicability of the model was further checked by the curves of drug concentration-time in blood and target organ(liver) of liver-targeting nanoparticles in animal tests. Based on the liver drug concentration-time curves calculated by the function formula of the drug in target organ, the pharmacokinetic behavior of the drug in target organ(liver) was analyzed by statistical moment, and its pharmacokinetic parameters in liver were obtained. It is suggested that the (relative targeting index( can be used for quantitative evaluation of the targeting drug delivery systems.

Recent advances in lymphatic targeted drug delivery system for tumor metastasis

The lymphatic system has an important defensive role in the human body. The metastasis of most tumors initially spreads through the surrounding lymphatic tissue and eventually forms lymphatic metastatic tumors; the tumor cells may even transfer to other organs to form other types of tumors. Clinically, lymphatic metastatic tumors develop rapidly. Given the limitations of surgical resection and the low effectiveness of radiotherapy and chemotherapy, the treatment of lymphatic metastatic tumors remains a great challenge. Lymph node metastasis may lead to the further spread of tumors and may be predictive of the endpoint event. Under these circumstances, novel and effective lymphatic targeted drug delivery systems have been explored to improve the specificity of anticancer drugs to tumor cells in lymph nodes. In this review, we summarize the principles of lymphatic targeted drug delivery and discuss recent advances in the development of lymphatic targeted carriers.

Insights on drug and gene delivery systems in liver fibrosis

Complications of the liver are amongst the world’s worst diseases.Liver fibrosis is the first stage of liver problems,while cirrhosis is the last stage,which can lead to death.The creation of effective anti-fibrotic drug delivery methods appears critical due to the liver’s metabolic capacity for drugs and the presence of insurmountable physiological impediments in the way of targeting.Recent breakthroughs in anti-fibrotic agents have substantially assisted in fibrosis;nevertheless,the working mechanism of anti-fibrotic medications is not fully understood,and there is a need to design delivery systems that are well-understood and can aid in cirrhosis.Nanotechnology-based delivery systems are regarded to be effective but they have not been adequately researched for liver delivery.As a result,the capability of nanoparticles in hepatic delivery was explored.Another approach is targeted drug delivery,which can considerably improve efficacy if delivery systems are designed to target hepatic stellate cells(HSCs).We have addressed numerous delivery strategies that target HSCs,which can eventually aid in fibrosis.Recently genetics have proved to be useful,and methods for delivering genetic material to the target place have also been investigated where different techniques are depicted.To summarize,this review paper sheds light on themost recent breakthroughs in drug and gene-based nano and targeted delivery systems that have lately shown useful for the treatment of liver fibrosis and cirrhosis.

Design and preparation of a new multi-targeted drug delivery system using multifunctional nanoparticles for co-delivery of siRNA and paclitaxel

Drug resistance is a great challenge in cancer therapy using chemotherapeutic agents. Administration of these drugs with siRNA is an efficacious strategy in this battle. Here, the present study tried to incorporate siRNA and paclitaxel(PTX) simultaneously into a novel nanocarrier. The selectivity of carrier to target cancer tissues was optimized through conjugation of folic acid(FA) and glucose(Glu) onto its surface. The structure of nanocarrier was formed from ternary magnetic copolymers based on FeCopolyethyleneimine(FeCo-PEI) nanoparticles and polylactic acid-polyethylene glycol(PLA-PEG) gene delivery system. Biocompatibility of FeCo-PEI-PLA-PEG-FA(NPsA), FeCo-PEI-PLA-PEG-Glu(NPsB) and FeCo-PEI-PLA-PEG-FA/Glu(NPsAB) nanoparticles and also influence of PTX-loaded nanoparticles on in vitro cytotoxicity were examined using MTT assay. Besides, siRNA-FAM internalization was investigated by fluorescence microscopy. The results showed the blank nanoparticles were significantly less cytotoxic at various concentrations. Meanwhile, siRNA-FAM/PTX encapsulated nanoparticles exhibited significant anticancer activity against MCF-7 and BT-474 cell lines. NPsAB/siRNA/PTX nanoparticles showed greater effects on MCF-7 and BT-474 cells viability than NPsA/siRNA/PTX and NPsB/siRNA/PTX.Also, they induced significantly higher anticancer effects on cancer cells compared with NPsA/siRNA/PTX and NPsB/siRNA/PTX due to their multi-targeted properties using FA and Glu. We concluded that NPsAB nanoparticles have a great potential for co-delivery of both drugs and genes for use in gene therapy and chemotherapy.

Delivering Microrobots in the Musculoskeletal System

Disorders of the musculoskeletal system are the major contributors to the global burden of disease and current treatments show limited efficacy.Patients often suffer chronic pain and might eventually have to undergo end-stage surgery.Therefore,future treatments should focus on early detection and intervention of regional lesions.Microrobots have been gradually used in organisms due to their advantages of intelligent,precise and minimally invasive targeted delivery.Through the combination of control and imaging systems,microrobots with good biosafety can be delivered to the desired area for treatment.In the musculoskeletal system,microrobots are mainly utilized to transport stem cells/drugs or to remove hazardous substances from the body.Compared to traditional biomaterial and tissue engineering strategies,active motion improves the efficiency and penetration of local targeting of cells/drugs.This review discusses the frontier applications of microrobotic systems in different tissues of the musculoskeletal system.We summarize the challenges and barriers that hinder clinical translation by evaluating the characteristics of different microrobots and finally point out the future direction of microrobots in the musculoskeletal system.

Membrane-coated nanoparticles as a biomimetic targeted delivery system for tumour therapy

Drug therapy towards tumours often causes adverse effects because of their non-specific nature.Membrane-coated technology and membrane-coated nanoparticles provide an advanced and promising platform of targeted and safe delivery.By camouflaging the nanoparticles with natural derived or artificially modified cell membranes,the nano-payloads are bestowed with properties from cell membranes such as longer circulation,tumour or inflammation-targeting,immune stimulation,augmenting the performance of traditional therapeutics.In this review,we review the development of membrane coating technology,and summarise the technical details,physicochemical properties,and research status of membrane-coated nanoparticles from different sources in tumour treatment.Finally,we also look forward to the prospects and challenges of transforming membrane coating technology from experiment into clinical use.Taken together,membrane-coated nanoparticles are bound to become one of the most potential anti-tumour strategies in the future.

Brain delivering RNA-based therapeutic strategies by targeting mTOR pathway for axon regeneration after central nervous system injury

Injuries to the central nervous system(CNS)such as stroke,brain,and spinal cord trauma often result in permanent disabilities because adult CNS neurons only exhibit limited axon regeneration.The brain has a surprising intrinsic capability of recovering itself after injury.However,the hostile extrinsic microenvironment significantly hinders axon regeneration.Recent advances have indicated that the inactivation of intrinsic regenerative pathways plays a pivotal role in the failure of most adult CNS neuronal regeneration.Particularly,substantial evidence has convincingly demonstrated that the mechanistic target of rapamycin(mTOR)signaling is one of the most crucial intrinsic regenerative pathways that drive axonal regeneration and sprouting in various CNS injuries.In this review,we will discuss the recent findings and highlight the critical roles of mTOR pathway in axon regeneration in different types of CNS injury.Importantly,we will demonstrate that the reactivation of this regenerative pathway can be achieved by blocking the key mTOR signaling components such as phosphatase and tensin homolog(PTEN).Given that multiple mTOR signaling components are endogenous inhibitory factors of this pathway,we will discuss the promising potential of RNA-based therapeutics which are particularly suitable for this purpose,and the fact that they have attracted substantial attention recently after the success of coronavirus disease 2019 vaccination.To specifically tackle the blood-brain barrier issue,we will review the current technology to deliver these RNA therapeutics into the brain with a focus on nanoparticle technology.We will propose the clinical application of these RNA-mediated therapies in combination with the brain-targeted drug delivery approach against mTOR signaling components as an effective and feasible therapeutic strategy aiming to enhance axonal regeneration for functional recovery after CNS injury.

Macrophage membrane-mediated targeted drug delivery for treatment of spinal cord injury regardless of the macrophage polarization states

Targeted delivery of therapeutics for spinal cord injury(SCI)has been a long-term challenge due to the complexity of the pathological procession.Macrophage,as an immune cell,can selectively accumulate at the trauma site after SCI.This intrinsic targeting,coupled with good immune-escaping capacity makes macrophages an ideal source of biomimetic delivery carrier for SCI.Worth mentioning,macrophages have multiple polarization states,which may not be ignored when designing macrophage-based delivery systems.Herein,we fabricated macrophage membrane-camouflaged liposomes(RM-LIPs)and evaluated their abilities to extend drug circulation time and target the injured spinal cord.Specially,we detected the expression levels of the two main targeted receptors Mac-1 and integrinα4 in three macrophage subtypes,including unactivated(M0)macrophages,classically activated(M1)macrophages and alternatively activated(M2)macrophages,and compared targeting of these macrophage membrane-coated nanoparticles for SCI.The macrophage membrane camouflage decreased cellular uptake of liposomes in RAW264.7 immune cells and strengthened binding of the nanoparticle to the damaged endothelial cells in vitro.RM-LIPs can prolong drug circulation time and actively accumulate at the trauma site of the spinal cord in vivo.Besides,RM-LIPs loaded with minocycline(RM-LIP/MC)showed a comprehensive therapeutic effect on SCI mice,and the anti-pyroptosis was found to be a novel mechanism of RM-LIP/MC treatment of SCI.Moreover,the levels of Mac-1 and integrinα4 in macrophages and the targeting of RM-LIP for SCI were found to be independent of macrophage polarization states.Our study provided a biomimetic strategy via the biological properties of macrophages for SCI targeting and treatment.

In Vitro Targeted Magnetic Delivery and Tracking of Superparamagnetic Iron Oxide Particles Labeled Stem Cells for Articular Cartilage Defect Repair

To assess a novel cell manipulation technique of tissue engineering with respect to its ability to augment superparamagnetic iron oxide particles （SPIO） labeled mesenchymal stem cells （MSCs） density at a localized cartilage defect site in an in vitro phantom by applying magnetic force. Meanwhile, non-invasive imaging techniques were use to track SPIO-labeled MSCs by magnetic resonance imaging （MRI）. Human bone marrow MSCs were cultured and labeled with SPIO. Fresh degenerated human osteochondral fragments were obtained during total knee arthroplasty and a cartilage defect was created at the center. Then, the osteochondral fragments were attached to the sidewalls of culture flasks filled with phosphate-buffered saline （PBS） to mimic the human joint cavity. The SPIO-labeled MSCs were injected into the culture flasks in the presence of a 0.57 Tesla （T） magnetic force. Before and 90 min after cell targeting, the specimens underwent T2-weighted turbo spin-echo （SET2WI） sequence of 3.0 T MRI. MRI results were compared with histological findings. Macroscopic observation showed that SPIO-labeled MSCs were steered to the target region of cartilage defect. MRI revealed significant changes in signal intensity （P0.01）. HE staining exibited that a great number of MSCs formed a three-dimensional （3D） cell ＂sheet＂ structure at the chondral defect site. It was concluded that 0.57 T magnetic force permits spatial delivery of magnetically labeled MSCs to the target region in vitro. High-field MRI can serve as an very sensitive non-invasive technique for the visualization of SPIO-labeled MSCs.

Layered Double Hydroxide Modified by PEGylated Hyaluronic Acid as a Hybrid Nanocarrier for Targeted Drug Delivery

In recent years, organic-inorganic hybrid nanocarriers are explored for effective drug delivery and preferable disease treatments. In this study, using 5-fluorouracil(5-FU)as electronegative model drug, a new type of organic-inorganic hybrid drug delivery system(LDH/HA-PEG/5-FU)was conceived and manufactured by the adsorption of PEGylated hyaluronic acid(HA-PEG)on the surface of layered double hydroxide(LDH, prepared via hydrothermal method)and the intercalation of 5-FU in the interlamination of LDH via ion exchange strategy. The drug loading amount of LDH/HA-PEG/5-FU achieved as high as 34.2%. LDH, LDH/5-FU and LDH/HA-PEG/5-FU were characterized by FT-IR, XRD, TGA, laser particle size analyzer and SEM. With the benefit of p Hdegradable feature of LDH and enzyme-degradable feature of HA, LDH/HA-PEG/5-FU showed p H-degradable and enzyme-degradable capacity in in vitro drug release. Moreover, the drug carrier LDH/HA-PEG contained biocompatible PEG and tumor-targeted HA, resulting in lower cytotoxicity and better endocytosis compared with LDH in vitro. It was suggested that the organic-inorganic hybrid drug delivery system, which was endowed with the properties of controlled release, low toxicity and tumor-targeting delivery for ameliorative cancer therapy, was advisable and might be applied further to fulfill other treatments.

pH-sensitive polymeric nanocarriers for antitumor biotherapeutic molecules targeting delivery

pH-sensitive smart polymeric nanocarriers have been under development in the field ofbiomedicine due to permeabilization the physiological barriers readily to address the limitation of conventional chemotherapeutics delivery systems of low intracellular transport and targeting efficiency.Where traditional polymers kept stable under physiological neutral or acidic conditions,pH-sensitive polymeric nanocarriers underwent rapid degradation with a labile group in tumor acidic environment(around 5.0-6.0),allowing these biomaterials to achieve controlled drug release,drug pharmacokinetics improvement and antitumor biotherapeutic molecules efficiency enhancement compared with traditional polymers.This review mainly concentrated on properties of pH-sensitive polymers for biomedical purposes to construct the smart drug delivery system based on acid liable linkers which were categorized into pH-sensitive polymeric prodrugs composed of antitumor drugs(doxorubicin and paclitaxel)bounded to the polymer via acid liable linkers and pH-sensitive copolymeric nanocarriers prepared by block copolymers containing polymer blocks linked with acid-cleavable groups.Besides,advanced platforms in biomedicine for special biotherapeutic molecules delivery were reviewed in the article.Furthermore,several acid-sensitive linkages were reviewed to study the mechanism of the controlled pH-responsive drug delivery,such as hydrazone,acetal,cis-aconityl linker and β-thioether ester,as well as improvement of drug pharmacokinetics.

Glycyrrhizic Acid-Targeted Carbon Nanotube Nanocomposites with Polyethylenimines-Mediated for Cancer Drug Delivery

In order to enhance the efficiency and specificity of anticancer drug delivery and realize intelligently controlled release,a new multi-functional nanoparticle drug carrier was synthesized.The drug carrier was prepared by functionalizing multi-walled carbon nanotubes(MWCNTs) with polyethylenimines(PEI),fluorescein isothiocyanate(FITC) and glycyrrhizic acid(GL).After detailed characterization,doxorubicin(DOX) was loaded onto the obtained MWCNT composites through π-π stacking interactions.The drug loading capacity of the GL-functionalized material was up to 92%,and the release behavior was significantly pH-sensitive.Release at pH = 5.8(typical of the tumor cell microenvironment) was much more rapid and reached a greater extent than release under normal physiological conditions(pH = 7.4).The modified MWCNTs had high biocompatibility with the liver cancer cell line SMMC-7721,but were able to induce cell death after 24 h incubation if loaded with DOX.Tests with shorter incubation time(2 h) were undertaken to investigate the selectivity of the MWCNT composites,showed that the nanocomposites could specifically target cancer cells.The above results suggest that the functionalized carbon nanotubes-based material has potential applications for targeted delivery and controlled release of anticancer drug.

Phytoestrogen-derived multifunctional ligands for targeted therapy of breast cancer

Nano-targeted delivery systems have been widely used for breast tumor drug delivery.Estrogen receptors are considered to be significant drug delivery target receptors due to their overexpression in a variety of tumor cells.However,targeted ligands have a significant impact on the safety and effectiveness of active delivery systems,limiting the clinical transformation of nanoparticles.Phytoestrogens have shown good biosafety characteristics and some affinity with the estrogen receptor.In the present study,molecular docking was used to select tanshinone IIA(Tan IIA)among phytoestrogens as a target ligand to be used in nanodelivery systems with somemodifications.Modified Tan IIA(Tan-NH2)showed a good biosafety profile and demonstrated tumor-targeting,anti-tumor and anti-tumor metastasis effects.Moreover,the ligand was utilized with the anti-tumor drug Dox-loaded mesoporous silica nanoparticles via chemical modification to generate a nanocomposite Tan-Dox-MSN.Tan-Dox-MSN had a uniform particle size,good dispersibility and high drug loading capacity.Validation experiments in vivo and in vitro showed that it also had a better targeting ability,anti-tumor effect and lower toxicity in normal organs.These results supported the idea that phytoestrogens with high affinity for the estrogen receptor could improve the therapeutic efficacy of nano-targeted delivery systems in breast tumors.

Magnetic Nano-Amorphous-Iron-Oxide-Based Drug Delivery System with Dual Therapeutic Mechanisms

Smart nanoparticles that respond to pathophysiological parameters,such as p H,GSH,and H2O2,have been developed with the huge and urgent demand for the high-efficient drug delivery systems(DDS)for cancer therapy.Herein,cubic poly(ethylene glycol)(PEG)-modified mesoporous amorphous iron oxide(AFe)nanoparticles(AFe-PEG)have been successfully prepared as p H-stimulated drug carriers,which can combine doxorubicin(DOX)with a high loading capacity of 948 mg/g,forming a novel multifunctional AFe-PEG/DOX nanoparticulate DDS.In an acidic microenvironment,the AFe-PEG/DOX nanoparticles will not only release DOX efficiently,but also release Fe ions to catalyze the transformation of H2O2 to·OH,acting as fenton reagents.In vitro experimental results proved that the AFe-PEG/DOX nanoparticles can achieve combination of chemotherapeutic(CTT)and chemodynamic therapeutic(CDT)effects on Hela tumor cells.Furthermore,the intrinsic magnetism of AFePEG/DOX makes its cellular internalization efficiency be improved under an external magnetic field.Therefore,this work develops a new and promising magnetically targeted delivery and dual CTT/CDT therapeutic nano-medicine platform based on amorphous iron oxide.

Hydrodynamic modeling of ferrofluid flow in magnetic targeting drug delivery

Among the proposed techniques for delivering drugs to specific locations within human body, magnetic drug targeting prevails due to its non-invasive character and its high targeting efficiency. Magnetic targeting drug delivery is a method of carrying drug-loaded magnetic nanoparticles to a target tissue target under the applied magnetic field. This method increases the drug concentration in the target while reducing the adverse side-effects. Although there have been some theoretical analyses for magnetic drug targeting, very few researchers have addressed the hydrodynamic models of magnetic fluids in the blood vessel. A mathematical model is presented to describe the hydrodynamics of ferrofiuids as drug carriers flowing in a blood vessel under the applied magnetic field. In this model, magnetic force and asymmetrical force are added, and an angular momentum equation of magnetic nanoparticles in the applied magnetic field is modeled. Engineering approximations are achieved by retaining the physically most significant items in the model due to the mathematical complexity of the motion equations. Numerical simulations are performed to obtain better insight into the theoretical model with computational fluid dynamics. Simulation results demonstrate the important parameters leading to adequate drug delivery to the target site depending on the magnetic field intensity, which coincident with those of animal experiments. Results of the analysis provide important information and suggest strategies for improving delivery in clinical application.

Process Modeling of Ferrofluids Flow for Magnetic Targeting Drug Delivery

Among the proposed techniques for delivering drugs to specific sites within the human body, magnetic targeting drug delivery surpasses due to its non-invasive character and its high targeting efficiency. Although there have been some analyses theoretically for magnetic drug targeting, very few researchers have addressed the hydrodynamic models of magnetic fluids in the blood vessel of human body. This paper presents a mathematical model to describe the hydrodynamics of ferrofluids as drug carriers flowing in a blood vessel under the applied magnetic field. A 3D flow field of magnetic particles in a blood vessel model is numerically simulated in order to further understand clinical application of magnetic targeting drug delivery. Simulation results show that magnetic nanoparticles can be enriched in a target region depending on the applied magnetic field intensity. Magnetic resonance imaging confirms the enrichment of ferrofluids in a desired body tissue of Sprague-Dawley rats. The simulation results coincide with those animal experiments. Results of the analysis provide the important information and can suggest strategies for improving delivery in favor of the clinical application.

Performance Analysis of Magnetic Nanoparticles during Targeted Drug Delivery:Application of OHAM

In recent years,the emergence of nanotechnology experienced incredible development in the field of medical sciences.During the past decade,investigating the characteristics of nanoparticles during fluid flow has been one of the intriguing issues.Nanoparticle distribution and uniformity have emerged as substantial criteria in both medical and engineering applications.Adverse effects of chemotherapy on healthy tissues are known to be a significant concern during cancer therapy.A novel treatment method of magnetic drug targeting(MDT)has emerged as a promising topical cancer treatment along with some attractive advantages of improving efficacy,fewer side effects,and reduce drug dose.During magnetic drug targeting,the appropriate movement of nanoparticles(magnetic)as carriers is essential for the therapeutic process in the blood clot removal,infection treatment,and tumor cell treatment.In this study,we have numerically investigated the behavior of an unsteady blood flowinfused with magnetic nanoparticles during MDT under the influence of a uniform external magnetic field in a microtube.An optimal homotopy asymptotic method(OHAM)is employed to compute the governing equation for unsteady electromagnetohydrodynamics flow.The influence of Hartmann number(Ha),particle mass parameter(G),particle concentration parameter(R),and electro-osmotic parameter(k)is investigated on the velocity of magnetic nanoparticles and blood flow.Results obtained show that the electro-osmotic parameter,along with Hartmann’s number,dramatically affects the velocity of magnetic nanoparticles,blood flow velocity,and flow rate.Moreover,results also reveal that at a higher Hartman number,homogeneity in nanoparticles distribution improved considerably.The particle concentration andmass parameters effectively influence the capturing effect on nanoparticles in the blood flow using a micro-tube for magnetic drug targeting.Lastly,investigation also indicates that the OHAM analysis is efficient and quick to handle the system of nonlinear equations.

Effect of minocycline and its nano-formulation on central auditory system in blast-induced hearing loss rat model

Blast injuries are common among the military service members and veterans.One of the devastating effects of blast wave induced TBI is either temporary or permanent hearing loss.Treating hearing loss using minocycline is restricted by optimal drug concentration,route of administration,and its half-life.Therefore,therapeutic approach using novel therapeutic delivery method is in great need.Among the different delivery methods,nanotechnology-based drug delivery is desirable,which can achieve longer systemic circulation,pass through some biological barriers and specifically targets desired sites.The current study aimed to examine therapeutic effect of minocycline and its nanoparticle formulation in moderate blast induced hearing loss rat model through central auditory system.The I.v.administered nanoparticle at reduced dose and frequency than regularly administered toxic dose.After moderate blast exposure,rats had hearing impairment as determined by ABR at 7-and 30-days post exposure.In chronic condition,free minocycline also showed the significant reduction in ABR threshold.In central auditory system,it is found in this study that minocycline nanoparticles ameliorate excitation in inferior colliculus;and astrocytes and microglia activation after the blast exposure is reduced by minocycline nanoparticles administration.The study demonstrated that in moderate blast induced hearing loss,minocycline and its nanoparticle formulation exhibited the optimal therapeutic effect on the recovery of the ABR impairment and a protective effect through central auditory system.In conclusion,targeted and non-targeted nanoparticle formulation have therapeutic effect on blast induced hearing loss.