Intranasal administration of stem cell-derived exosomes for central nervous system diseases

Exosomes,lipid bilayer-enclosed small cellular vesicles,are actively secreted by various cells and play crucial roles in intercellular communication.These nanosized vesicles transport internalized proteins,mRNA,miRNA,and other bioactive molecules.Recent findings have provided compelling evidence that exosomes derived from stem cells hold great promise as a therapeutic modality for central nervous system disorders.These exosomes exhibit multifaceted properties including antiapoptotic,anti-inflammatory,neurogenic,and vasculogenic effects.Furthermore,exosomes offer several advantages over stem cell therapy,such as high preservation capacity,low immunogenicity,the ability to traverse the blood-brain barrier,and the potential for drug encapsulation.Consequently,researchers have turned their attention to exosomes as a novel therapeutic avenue.Nonetheless,akin to the limitations of stem cell treatment,the limited accumulation of exosomes in the injured brain poses a challenge to their clinical application.To overcome this hurdle,intranasal administration has emerged as a non-invasive and efficacious route for delivering drugs to the central nervous system.By exploiting the olfactory and trigeminal nerve axons,this approach enables the direct transport of therapeutics to the brain while bypassing the blood-brain barrier.Notably,exosomes,owing to their small size,can readily access the nerve pathways using this method.As a result,intranasal administration has gained increasing recognition as an optimal therapeutic strategy for exosomebased treatments.In this comprehensive review,we aim to provide an overview of both basic and clinical research studies investigating the intranasal administration of exosomes for the treatment of central nervous system diseases.Furthermore,we elucidate the underlying therapeutic mechanisms and offer insights into the prospect of this approach.

Case of Advanced Recurrent Glioblastoma Successfully Treated with Monoterpene Perillyl Alcohol by Intranasal Administration

We report a case of recurrent glioblastoma (GBM) successfully treated with the Ras inhibitor monoterpene perillyl alcohol by intranasal administration. A 37-years-old white woman had been previously submitted to three neurosurgical procedures, in June 2000 for radical tumor excision of grade II astrocytoma;in July 2003 for first recurrence of type IV glioma and in August 2004 for GBM recurrence. After last surgery, patient started a new cycle of chemotherapy but was refractory to treatment, presented clinical adverse effects and resonance image scan showed no reduction of tumoral lesion. Patient was then considered out of therapeutic possibilities and indicated for supportive treatment. On March 2005 patient joined Phase I/II clinical trial for assess the efficacy of the monoterpene POH, a Ras inhibitor. POH was administered by intranasal route four times a day (268 mg daily) as single chemotherapy agent. Image scans performed 3 and 5 years later revealed marked reduction of enhancing lesion. This illustrative case demonstrates that intranasal administration of the monoterpene POH as a single agent was an effective therapeutic strategy capable to sustain long-term regression of recurrent glioma without clinical and laboratory toxicity.

Comparison of pharmacokinetics of Alprazolam after intranasal and intragastric administration in rats

Objective To compare the pharmacokinetics of Alprazolam after intranasal and intragastic administration in rats and evaluate the practicability of Alprazolam as a nasal drug delivery system.Methods 12 rats were randomly divided into two groups.The fate of drug in the serum of rats was monitered after intranasal and intragastic administration of Alprazolam 2 mg·kg-1.Serum levels of Alprazolam were determined by reversed-phase HPLC with Diode array detectors(DAD).Chromatographic conditions were adopted with ODS column as solid phase,methanaol-0.02 M ammonium acetate(pH=5.0)(60∶40)as mobile phase at a flow rate of 1.0 mL·min-1.The detection wavelength was 223 nm.The concentration-time data were analyzed using 3P87 program,and the pharmacokinetic parameters were compared by t-test.Results The pharmacokinetic characteristics were fit to two and one compartment opened model after intranasal and intragastic administration of Alprazolam,respectively.The drug absorption was quicker and the serum concentrations of Alprazolam was significantly higher in rats after intranasal administration group than that intragastic administration group(P<0.05).The eliminate parameters between the two groups were no significant difference(P>0.05).Means of pharmacokinetic parameters in intranasal and intragastic groups were:Ka 37.35±22.98 vs 11.57±12.47 h-1(P<0.05),t1/2ka0.025±0.013 vs 0.156±0.122 h(P<0.05),β(Ke)0.3131±0.1194 vs 0.3091±0.1216 h-1(P>0.05),t1/2β(t1/2Ke)2.51±0.99 vs 2.54±0.97 h(P>0.05),tmax 0.156±0.069 vs 0.618±0.414 h(P<0.01),Cmax 353.11±96.30 vs 62.09±35.08 μg·L-1(P<0.01),AUC 1111.6±473.2 vs 274.1±185.3 μg·L-1·h(P<0.01).Conclusions Alprazolam was absorbed quickly in rats after intranasal administration.And the serum concentration and bioavailability can be significantly increased after intranasal administration,which may be an effective preparation as nasal drug delivery system.

Protective effects of resveratrol nanosuspensions loaded in situ hydrogel on Alzheimer disease model mice after intranasal administration

OBJECTIVE To evaluate the protective effects of resveratrol nanosuspensions loaded in situ hydrogel on Alzheimer disease model mice after intranasal administration. METHODS Resveratrol nanosuspensions were fabricated by antisolvent nano-precipitation method,and then dispersed into0.5% gellan gum to form resveratrol nanosuspenisons loaded ionic sensitive in situ hydrogel. The Alzheimer′s disease models were induced by lateral ventricle injection of Aβ_(25~35)and the protection and treatment effects of resveratrol nanosuspensions loaded in situ hydrogel on study and memory capability were performed after intranasal administration in water maze experiments. The analyses of the changes of cholinergic neurotransmitters in the brain were also determined according to the contents of acetylcholine(ACh),choline acetyltransferase(ChAT) and acetylcholinesterase(AChE). RESULTS Behavior assessment disclosed that in position navigation,escape latency test,each of experimental animals showed a decreased trend with swim training days increase,indicating that in the training process they had the ability of learning and memory in looking for the platform. Compared with the control group,average latency of model group significantly increased. While compared with the model group,treatment group′s average latency was significantly shorter. Space exploration experiment results showed that the times of model group across target quadrant of the platform is less than that of control group. But the crossing times of treatment group with resveratrol increased compared with the model group. As for the changes of cholinergic neurotransmitters,in AD mice brain ACh content decreased; the Ch AT activity decreased,while the activity of ACh E with the ability to hydrolysis acetylcholine increased. The administration of resveratrol can decrease the activity of ACh enzymes but increase Ch AT activity and the levels of acetylcholine. CONCLUSION Resveratrol nanosuspension loaded in situ gel can ameliorate the declining ability of learning and memory of AD model mice after intranasal administration. As a promising approach for the treatment of central nervous system(CNS) disease,intranasal administration route can effectively deliver to the brain and thus enhance the therapeutic effect.

Nasal Dermoid Cyst with Sinus Tract Intranasal Bone: A Case Report

Dermoid cysts are benign tumors originating from germ cells, which can form in various locations, including the nasal area in rare cases. They are of unknown exact etiology, but it is suggested that it is due to abnormal tissue migration during early embryonic development. Nasal dermoid cysts albeit rare, can present in various forms such as sinuses, fistulas, or intracranially extending tracts. They can be asymptomatic and incidentally discovered or present with a visible external mass or sinus that is either painful, infected or cosmetically concerning. If nasal dermoid cysts with an intra-nasal bone sinus tract are left untreated, they can lead to life-threatening complications. This report describes the case of a 6-year-old girl with a nasal dermoid cyst connected to a superficial punctum by an intra-nasal tract. She had undergone surgical excision of a nasal swelling previously diagnosed as a dermoid cyst. One year later, she returned to our clinic with a recurrence of the nasal swelling. Imaging tests revealed a nasal dermoid cyst with a tract extending to the nasal tip, without intracranial expansion. The cyst, along with the entire tract, was successfully removed surgically, and the postoperative follow-up indicated no complications. Histopathology confirmed the diagnosis of a dermoid cyst. This case underscores the significance of considering the dermoid tract in nasal cyst cases and the necessity of its complete removal to prevent recurrence.

The Development Trend of Enterprise Business Administration and the Innovation of Management Mode

In the context of the new period,the continuous growth of social and economic levels and the rapid update of information technology have significantly impacted the business management of Chinese enterprises,presenting substantial challenges.The intensification of market competition exerts development pressure on many enterprises,and coupled with the unstable strength of some businesses,numerous problems in business management arise.These issues hinder the smooth execution of various business activities.Therefore,it is crucial to ensure effective business administration to conduct different business activities in an orderly manner,promptly avoid adverse risks,and strengthen control over multiple factors.The innovation and improvement of business administration are of great significance for enhancing the management level and market competitiveness of modern enterprises,accelerating their healthy development,and creating numerous opportunities.Consequently,this paper analyzes and explores the development trends of enterprise business administration and the innovation of management models for reference.

Exploring Corporate Tax Compliance in the Era of Digital Tax Collection and Administration:Insights from the“Golden Tax Phase Four”Project

This article primarily examines the current state of tax collection and management,alongside other associated issues.It integrates insights from China’s“14th Five-Year Plan”and anticipates the imminent implementation of the“Golden Tax Phase Four.”With this backdrop,the article offers recommendations for advancing the reform of the tax collection and management system,fostering the development of intelligent taxation,and accelerating the modernization of tax collection and management in China.

HR121 targeting HR2 domain in S2 subunit of spike protein can serve as a broad-spectrum SARS-CoV-2 inhibitor via intranasal administration

The continuously emerging SARS-CoV-2 variants pose a great challenge to the efficacy of current drugs,this necessitates the development of broad-spectrum antiviral drugs.In the previous study,we designed a recombinant protein,heptad repeat(HR)121,as a variant-proof vaccine.Here,we found it can act as a fusion inhibitor and demonstrated broadly neutralizing activities against SARS-CoV-2 and its main variants.Structure analysis suggested that HR121 targets the HR2 domain in SARS-CoV-2 spike(S)2 subunit to block virus-cell fusion.Functional experiments demonstrated that HR121 can bind HR2 at serological-pH and endosomal-pH,highlighting its inhibition capacity when SARS-CoV-2 enters via either cellular membrane fusion or endosomal route.Importantly,HR121 can effectively inhibit SARS-CoV-2 and Omicron variant pseudoviruses entering the cells,as well as block authentic SARSCoV-2 and Omicron BA.2 replications in human pulmonary alveolar epithelial cells.After intranasal administration to Syrian golden hamsters,it can protect hamsters from SARS-CoV-2 and Omicron BA.2 infection.Together,our results suggest that HR121 is a potent drug candidate with broadly neutralizing activities against SARS-CoV-2 and its variants.

Exploring the potential to enhance drug distribution in the brain subregion via intranasal delivery of nanoemulsion in combination with borneol as a guider

The number of people with Alzheimer’s disease(AD)is increasing annually,with the nidus mainly concentrated in the cortex and hippocampus.Despite of numerous efforts,effective treatment of AD is still facing great challenges due to the blood brain barrier(BBB)and limited drug distribution in the AD nidus sites.Thus,in this study,using vinpocetine(VIN)as a model drug,the objective is to explore the feasibility of tackling the above bottleneck via intranasal drug delivery in combination with a brain guider,borneol(BOR),using nanoemulsion(NE)as the carrier.First of all,the NE were prepared and characterized.In vivo behavior of the NE after intranasal administration was investigated.Influence of BOR dose,BOR administration route on drug brain targeting behavior was evaluated,and the influence of BOR addition on drug brain subregion distribution was probed.It was demonstrated that all the NE had comparable size and similar retention behavior after intranasal delivery.Compared to intravenous injection,improved brain targeting effect was observed by intranasal route,and drug targeting index(DTI)of the VIN–NE group was 154.1%,with the nose-to-brain direct transport percentage(DTP)35.1%.Especially,remarkably enhanced brain distribution was achieved after BOR addition in the NE,with the extent depending on BOR dose.VIN brain concentration was the highest in the VIN-1-BOR-NE group at BOR dose of 1 mg/kg,with the DTI reaching 596.1%and the DTP increased to 83.1%.BOR could exert better nose to brain delivery when administrated together with the drug via intranasal route.Notably,BOR can remarkably enhance drug distribution in both hippocampus and cortex,the nidus areas of AD.In conclusion,in combination with intranasal delivery and the intrinsic brain guiding effect of BOR,drug distribution not only in the brain but also in the cortex and hippocampus can be enhanced significantly,providing the perquisite for improved therapeutic efficacy of AD.

Intranasal administration nanosystems for brain-targeted drug delivery

The existence of the blood-brain barrier(BBB)restricts the entry of drugs from the circulation into the central nervous system(CNS),which severely affects the treatment of neurological diseases,including glioblastoma,Parkinson’s disease(PD),and Alzheimer’s disease(AD).With the advantage of bypassing the BBB and avoiding systemic distribution,intranasal administration has emerged as an alternative method of delivering drugs to the brain.Drug delivery directly to the brain using intranasal nanosystems represents a new paradigm for neurological disease treatment because of its advantages in improving drug solubility and stability in vivo,enabling targeted drug delivery and controlled release,and reducing non-specific toxicity.And it has shown efficacy in animal models and clinical applications.Herein,this review describes the mechanisms of intranasal delivery of brain-targeted drugs,the properties of nanosystems for intranasal administration(e.g.,liposomes,nanoemulsions,and micelles),and strategies for intranasal drug delivery to enhance brain-targeted drug delivery.Recent applications of nanosystems in intranasal drug delivery and disease treatment have been comprehensively reviewed.Although encouraging results have been reported,significant challenges still need to be overcome to translate these nanosystems into clinics.Therefore,the future prospects of intranasal drug delivery nanosystems are discussed in depth,expecting to provide useful insights and guidance for effective neurological disease treatment.

Intranasal administration of induced pluripotent stem cell-derived cortical neural stem cell-secretome as a treatment option for Alzheimer’s disease

Background Alzheimer’s disease(AD)is the most common neurodegenerative disorder in the elderly,resulting in gradual destruction of cognitive abilities.Research on the development of various AD treatments is underway;however,no definitive treatment has been developed yet.Herein,we present induced pluripotent stem cell(iPSC)-derived cortical neural stem cell secretome(CNSC-SE)as a new treatment candidate for AD and explore its efficacy.Methods We first assessed the effects of CNSC-SE treatment on neural maturation and electromagnetic signal during cortical nerve cell differentiation.Then to confirm the efficacy in vivo,CNSC-SE was administered to the 5×FAD mouse model through the nasal cavity(5μg/g,once a week,4 weeks).The cell-mediated effects on nerve recovery,amyloid beta(Aβ)plaque aggregation,microglial and astrocyte detection in the brain,and neuroinflammatory responses were investigated.Metabolomics analysis of iPSC-derived CNSC-SE revealed that it contained components that could exert neuro-protective effects or amplify cognitive restorative effects.Results Human iPSC-derived CNSC-SE increased neuronal proliferation and dendritic structure formation in vitro.Furthermore,CNSC-SE-treated iPSC-derived cortical neurons acquired electrical network activity and action potential bursts.The 5×FAD mice treated with CNSC-SE showed memory restoration and reduced Aβplaque accumulation.Conclusions Our findings suggest that the iPSC-derived CNSC-SE may serve as a potential,non-invasive therapeutic option for AD in reducing amyloid infiltration and restoring memory.

Intranasal nerve growth factor for prevention and recovery of the outcomes of traumatic brain injury

Traumatic brain injury is one of the main causes of mortality and disability worldwide.Traumatic brain injury is characterized by a primary injury directly induced by the impact,which progresses into a secondary injury that leads to cellular and metabolic damages,starting in the first few hours and days after primary mechanical injury.To date,traumatic brain injury is not targetable by therapies aimed at preventing and/or limiting the outcomes of secondary damage but only by palliative therapies.Nerve growth factor is a neurotrophin targeting neuronal and non-neuronal cells,potentially useful in preventing/limiting the outcomes of secondary damage in traumatic brain injury.This potential has further increased in the last two decades since the possibility of reaching neurotrophin targets in the brain through its intranasal delivery has been exploited.Indeed,molecules intranasally delivered to the brain parenchyma may easily bypass the blood-brain barrier and reach their therapeutic targets in the brain,with favorable kinetics,dynamics,and safety profile.In the first part of this review,we aimed to report the traumatic brain injury-induced dysfunctional mechanisms that may benefit from nerve growth factor treatment.In the second part,we then exposed the experimental evidence relating to the action of nerve growth factor(both in vitro and in vivo,after administration routes other than intranasal)on some of these mechanisms.In the last part of the work,we,therefore,discussed the few manuscripts that analyze the effects of treatment with nerve growth factor,intranasally delivered to the brain parenchyma,on the outcomes of traumatic brain injury.

A Continuable Political Administration System for World Countries （II）

In this work, some important parts of the system, and the relation between the parts, and its connections with other systems are defined, explained briefly. With this respect, the nature of the person is defined with related parts. A new science branch called ＂information science＂ is defined. Importance of the political organizing of a political party is shortly explained. The necessity of the academies for public sector, private sector, and for political administration system is expressed. How to choose a person and how a person can be choose for any part of the system is defined. For both cases ＂good and/or correct＂ system criterions, determination of the criterions, and evaluation criterions are defined. New evaluation levels are defined based on the 8-basic senses in philosophical point of view to deepen the sensitivity of the evaluations. The importance of the situation notice and how to make it for each of the association are explained. The 10 main service parameters are defined to show the interactive relations between the ideology, services, person nature and others. Present and possible future problems of a country are expressed. Aims/targets are characterized with real approach for all related sides. Other systems which proposed to be connected to continuable political administration system are shortly defined and expressed. Way of system administration and administration types are shortly explained. The importance and ways of the decision making are expressed. The general ways, types of inspection are shortly explained. Official units that could be assign for the new system are defined. The importance of these units and of the persons that could be assign for these units are expressed together with the definition of the characteristics of the persons or groups that could be. The necessity of an action planning, possible supply and demand cases are defined scientifically. The importance and necessity of sense of justice is explained to make system continuable. The methods of determination of the policies/strategies are expressed.

A Continuable Political Administration System for World Countries （I）

In this work all the political/non-political ideologies, 168 religions/beliefs/sects, nearly 1,600 ethnic origin groups are synthesized to define continuable political construction. It is found that all the past federations, confederations, empires, ideologies, political administration systems, thoughts and senses, doctrines, etc. are in fact each reflects a special functional processes within a general system of where the kinds of services, subjects of services, way of services, service types and persons are considered and placed as a factor in it and where these factors are arranged through different priorities, weights, and also taken under record with some rules. It is evaluated that each groups, communities, societies, countries are separate models, but at the same time each of them are factors which owns different beginning points to reach a correct country structure with five new separate groups （New Era Group, Progression of The Country Group, Unity of The Country Group, Values of The Country Group, Social Progression Group）. The continuable political administration system is defined here by considering the all possible parts and by considering the other systems eormected for a country. Possible forceful factors which can effect political system administration are given. To realize political construction, some political construction methods are defined： Political construction by putting together the values, political construction based on different value, Political construction based on the new defined values, Political construction which considers stepped transition and Ideal political construction which will carry the political points of views and other standards of judgement, points of views of persons to a same line are expressed. New ideologies are put forwarded and ideal political construction for a world country is given with details. Integration of the political groups, political ideologies to the new system is explained. Some methods of politics are mentioned. Persons related with politics are classified simply.

America’s Policy towards China under Two Administrations in the Context of Great Changes: Difference, Influence and Enlightenment

Under the great changes unseen in a century,comprehensive containment and suppression of China in the name of strategic competition has become a crossparty consensus in the United States,with the Republican Trump administration initiating the process of containing and suppressing China and the Democratic Biden administration continuing and developing such a strategy.In the process of implementing this strategy,there are some diff erences in the goals and means of the two American administrations.The Trump administration was trying to“crush China”with the super strength of the United States,with more extreme and tougher means,being more unilateralist and even going so far as to launch a“new Cold War”against China.The Biden administration,on the other hand,emphasizes long-term competition with China,and focuses on“managing competition”while suppressing China,accustomed to being double-handed and using both carrot and stick.When it comes to addressing global challenges,the Republican Party completely lacks the will to cooperate with China,while the Democratic Party has a certain need for cooperation and action.

Application of Information Technology in Institutions and Challenges of Human Resources-Case Study: Administration of the Municipality of Ferizaj

This study aims to investigate how information technology is applied in the administration of the municipality of Ferizaj and what are the challenges with human resources, the work was carried out through a case study in the municipality. This paper highlights that the use of information technology provides higher efficiency for the performance of daily work in the municipality, thus also the provision of better services to citizens. However, the level of use of information technology in the Municipality of Ferizaj leaves much to be desired in terms of efficiency because a significant number of employees have not attended adequate training for the effective and efficient use of various IT applications and have not are still adapted to the digital environment in the municipality. Therefore, the recommendation derived from this paper is that the information technology environment in the municipality of Ferizaj needs to be improved by providing staff with adequate qualifications, while for those who are currently engaged in the municipality and who do not have adequate qualifications, training should be provided in a way that all users of IT applications are fully integrated into the digitized environment in order to be effective and efficient in providing services to citizens. This simultaneously gives the municipal staff job security and motivation for better services for citizens. Also, information technology enables a better control over the activity of the municipality because every action is recorded as data which can then be used to analyze the performance of the municipality.

Enhancing effect of natural borneol on the absorption of geniposide in rat via intranasal administration

Both geniposide （Ge） and natural borneol （NB） are bioactive substances derived from traditional Chinese herbs. The effect of NB on the pharmacokinetics of Ge in rat via intranasal administration was investigated. The concentrations of Ge in plasma were determined by reversed-phase high-performance liquid chromatography （HPLC） after intranasal administration of Ge （4 mg/kg） alone and combined with different doses （0.08, 0.8, and 8 mg/kg） of NB. The intravenous administration was given as a reference （4 mg/kg of Ge and 8 mg/kg of NB）. Compared with the intravenous administration, the absolute bioavailability of Ge was 76.14% through intranasal administration combined with NB. Compared with the intranasal administration of Ge alone, Ge could be absorbed rapidly in the nasal cavity combined with NB; the peak time of Ge in the plasma became shorter （3-5 min vs. 40 min）; the peak concentration became higher （1.32-4.25 IJg/ml vs. 0.67 ug/ml）; and, the relative bioavailability of Ge combined with NB was 90.3%-237.8%. The enhancing effect was attenuated as the dose of NB decreased. The results indicated that NB can accelerate the absorption of Ge dose-dependently in the nasal cavity.

Status, Transition, and Impact of the Yoon Suk-yeol Administration’s Trade Policy with China

China is Korea’s main trade partner in East Asia and one of its key economic and trade partners worldwide.The two countries have complementary industrial structure and a long history of trade exchanges.However,against the backdrop of a return to global trade protectionism and the politicization of international affairs with Yoon Suk-yeol coming to power,South Korea has undertaken a strong trade shift toward the United States(US),triggering a change in the pattern of economic cooperation in East Asia and challenging the regional trade structure.A review of the trade policy agenda of the Yoon Suk-yeol administration toward the US and China,along with a comparative review of Korea’s foreign trade stance under Moon Jae-in,allows for an analysis of the turnaround and characteristics of Yoon’s trade policy toward China during his tenure.The implications for global trade governance and regional security are further analyzed with an aim of finding a Nash equilibrium in trade cooperation among East Asian countries.

Design of an E-Administration Platform and Its Cryptography-Based Security Model

E-administration is performing administrative works via computer and its associated technologies such as the Internet. It is administrative efforts that center on the exchange of information and providing services to people and the business sector at high speed and low cost through computers and networks with the assurance of maintaining information security. It is based on the positive investment in information technology and communication in administrative practices. This paper presents the design of the e-administration platform that adopts the concept of cryptography for identity management. The architectural framework of the platform comprises subcomponents for service and forms identification, business process redesign, service architecture, amalgamation, and deployment. The cryptography model for securing the platform was designed based on the combination of authentication criteria presented in the Rijndael-Advanced Encryption Standard (AES), Lattice-based cryptography (LBC), and Secure Hash Algorithm (SHA512). It is required that a record be encrypted prior to its commitment to the database via a double encryption method. The AES algorithm-based encryption’s output will form the input to the LBC algorithm to obtain the final output.

Influence of the nasal mucociliary system on intranasal drug administration

To study the influence of the nasal mucociliary system on intranasal drug administration and ways of reducing its influence on nasal absorption Methods Rabbit nasopharynx was closed to stop mucociliary function in one group In the other group, rabbits maintained their mucociliary function Both groups were given a nasal drip of gentamycin and the serum levels were measured from 0 to 180 minutes after drug administration To reduce the undesirable effects of the nasal mucociliary system, acetylcysteine was mixed into the gentamycin drops In addition, nasal nebulization was evaluated in human volunteers as a means of increasing absorption of the drug in the non ciliary area of the nasal cavity Results Nasal mucociliary function reduced intranasal absorption of drug and made the highest absorbing rate and area under the curve (AUC) decrease by 25 1% and 18 2%, respectively Both the nasal drip containing acetylcysteine and the nebulizer could promote drug absorption in the nasal mucosa The former made the highest intranasal absorption and AUC increase by 18 0% and 10 7%, respectively The latter made the absorption increase 1 5-1 6 times Conclusion The mucociliary system can decrease intranasal drug absorption Application of acetylcysteine or the use of nebulizer can increase drug absorption