Oral administration microrobots for drug delivery

Oral administration is the most simple, noninvasive, convenient treatment. With the increasing demands on thetargeted drug delivery, the traditional oral treatment now is facing some challenges: 1) biologics how toimplement the oral treatment and ensure the bioavailability is not lower than the subcutaneous injections;2)How to achieve targeted therapy of some drugs in the gastrointestinal tract? Based on these two issues, drugdelivery microrobots have shown great application prospect in oral drug delivery due to their characteristics offlexible locomotion or driven ability. Therefore, this paper summarizes various drug delivery microrobotsdeveloped in recent years and divides them into four categories according to different driving modes: magneticcontrolleddrug delivery microrobots, anchored drug delivery microrobots, self-propelled drug delivery microrobotsand biohybrid drug delivery microrobots. As oral drug delivery microrobots involve disciplines such asmaterials science, mechanical engineering, medicine, and control systems, this paper begins by introducing thegastrointestinal barriers that oral drug delivery must overcome. Subsequently, it provides an overview of typicalmaterials involved in the design process of oral drug delivery microrobots. To enhance readers’ understanding ofthe working principles and design process of oral drug delivery microrobots, we present a guideline for designingsuch microrobots. Furthermore, the current development status of various types of oral drug delivery microrobotsis reviewed, summarizing their respective advantages and limitations. Finally, considering the significantconcerns regarding safety and clinical translation, we discuss the challenges and prospections of clinical translationfor various oral drug delivery microrobots presented in this paper, providing corresponding suggestions foraddressing some existing challenges.

In-situ Gelation of Sodium Alginate-chitosan for Oral Delivery of Probiotics

We developed a new preparation to protect probiotic cells from adverse environmental conditions and improve their livability,which is called Lactobacillus casei-Sodium alginate-Chitosan (LSC).The LSC was prepared by mixing probiotics with sodium alginate-chitosan sol.The preparation contained complex calcium ions,which were released in the acidic environment of gastric juice,thus crosslinking to form in-situ gel.Different proportions of sodium alginate-chitosan were prepared to add to simulate gastrointestinal fluid to get the best ratio.The optimal ratio of LSC preparation was compared with traditional gel microspheres to observe the survival effect of probiotics in gastrointestinal fluid environment.Compared with sodium alginate sol,the porosity of sodium alginate-chitosan sol is lower,which is beneficial to the protection of probiotics.When the ratio of chitosan to sodium alginate is 1.5:1.5 (w/v),the protective effect is the best.The protective ability of LSC is 64 times that of traditional microspheres,and it has the potential of synergistic anti-tumor.A probiotic preparation with simple preparation process and better protection effect compared with traditional microspheres was prepared,which has joint anti-tumor potential.

Clinical research progress of oral administration of traditional Chinese medicine in the treatment of dry eyes

Dry eye is a common and frequently occurring ophthalmology disease with complex etiology and easy recurrence.Oral administration of traditional Chinese medicine has the characteristicsof high curative effect and little toxic and side effect in the treatment of dry eye.This paper collates the domestic reported clinical studies on the oral administration of traditional Chinese medicine in the treatment of dry eye,which are discussed from four aspects:special prescription for specific disease,addition and subtraction of main prescription,treatment based on syndrome differentiation and proprietary Chinese medicine.The curative effect and advantages of traditional Chinese medicine in the treatment of dry eye are demonstrated,providing a reference for the treatment of dry eye in the future.

Clinical Observation on Treatment of Acquired Paralytic Strabismus by Acupuncture Plus Oral Administration of Chinese Herbs

From June 1996 to June 2002, the author treated 38 cases of acquired paralytic strabismus by acupuncture plus oral administration of Zheng Rong Tang (正容汤), with another 38 cases of acquired paralytic strabismus treated only with oral administration of Chinese herbs as the controls. The results are reported as follows.

Fifty-six Cases of Stubborn Eczema Treated by Oral Administration and Topical Application of Herbal Medicine

Eczema is a kind of very common dermatopathy. The cases with a long course of illness and hard to be cured are termed as stubborn eczema. We have obtained good results in its treatment since 1995 with the Chu Shi Tang (除湿汤Dampness-Clearing Decoction) for oral intake and the Fu Fang Ku Shen Xi Ye (复方苦参洗液) for topical application. The following is a clinical report for treating 56 patients with stubborn eczema.

A Study on Early Biological Effects of Oral Administration of Terephthalic Acid in Rats

Rats were fed with foods containing various doses of terephthalic (TPA) for 8 weeks. General status was observed and biological indices(including urine,serum and bone) were determined after 1, 3 and 8 week administration.Differences in urine calcium, ammonia, PH and serum albumin between the treat groups and the control were significant. Marked correlation was found in these indices. No Change in N-acetyl-β-D-glucosaminidase (NAG),serum calcium,bone calcium, alkaline phosphatase and alanine transaminase was noted in the treat groups.It suggests that change of urine ammonium concentration may serve as a protective level in setting the TPA exposure limit.

Pharmacokinetics of Milbemycin Oxime in Dogs Following Its Intravenous and Oral Administration

The pharmacokinetics of milbemycin oxime was investigated in dogs following oral(per os, PO) and intravenous(IV) administration. Three groups of dogs received milbemycin oxime tablets as a single PO dose equal to 0.25, 0.5 and 1.0 mg · kg-1 of milbemycin oxime, respectively, another group received a single IV dose of 0.5 mg · kg-1. Blood samples were collected at predetermined times after drug administration and the milbemycin oxime concentrations in plasma were determined by LC-MS/MS. The drug protein binding in dog plasma in vitro was determined by equilibrium dialysis at concentrations spanning the range of values observed in vivo in dog plasma. After PO administration at doses of 0.25, 0.5 and 1.0 mg · kg-1, milbemycin oxime was slowly absorbed and eliminated, the time to reach the maximum plasma concentration(Tmax) was 4.14±0.20, 4.27±0.14 and 4.06±0.13 h, the mean absorption time(MAT) was 19.06, 13.67 and 11.77 h, the terminal rate half-life(t1/2λz) was 15.06±0.37, 11.09±0.54 and 9.76±0.89 h and the total body clearance(Cl) was 1.15±0.05, 1.18±0.03 and 1.17±0.07 m L · min-1 · kg-1, respectively. The maximum plasma concentration(Cmax, 36.50±1.40, 76.11±2.77 and 182.05±7.20 ng · m L-1, respectively) and the area under the first-moment curve(AUC-10→∞, 985.83±49.46, 1 663.12±51.42 and 3 558.04±197.88 mg · h · L, respectively) increased accordingly to the administered dose rates; the oral bioavailabilities were estimated to be 88.61%, 74.75% and 79.96%, respectively. The values of fu were 0.12%, 0.14% and 0.13% in dog plasma, respectively. In conclusion, the pharmacokinetics of milbemycin oxime in dogs following oral administration revealed its higher oral bioavailability and advantageous pharmacokinetic properties, such as its lower total body clearance and longer elimination half-life, and indicated that the single oral dose of 0.50 mg · kg-1 of milbemycin oxime which was recommended in all the parasitological efficacy studies allowed an adequate concentration of the drug.

Acute Toxicity of Aluminium Phosphide Following Oral Administration in Rats

Aluminium phosphide (AlP) is used as a fumigant and also sometimes misused for suicidal attempts in India, due to its easy availability. The effect of phosphine, the gas that is liberated when AlP comes in contact with moisture, is well documented in the literature. However, the effect of AlP in its native form on animal models is not well cited. In this study we examined the acute toxic effect of AlP in rats. Oral LD50 of AlP for male and female rats were found to be 14. 13 and 11. 89mg/kg, respectively. Oral administration of an AlP dose of 0. 80 LD50 resulted in significant increases in the level of plasma glutamic oxaloacetic transaminase,alkaline phosphatase, glucose and urea in rats of both sexes. Hemoglobin level and packed cell volume also increased significantly 6h after administration. Body weight was reduced but the organ to body weight ratio of lung, liver, spleen, kidney and testes remained unchanged.Histopathological changes induced by AlP during 24-48h induced hemorrhage, congestion and mild to moderate atrophy of various cellular components of visceral organs. The study showed that the acute toxic effect of AlP may be due to hypovolemic shock. Female rats were found to be more susceptible than were males.

Treatment of Irritable Bowel Syndrome by Oral Administration of Chinese Medicines and Retention-Enema——A Report of 50 Cases

Irritable bowel syndrome (IBS), a common disease of intestinal dysfunction, is also called emotional enteritis, mucous enteritis, irritable colon and so on1. It is often lingering with a long disease course and is easy to recur. The author has in recent years treated 50 cases of the disease by oral administration of Chinese medicines and retention-enema, with satisfactory results reported as follows.

EVALUATION OF ORAL MIDAZOLAM AS CONSCIOUS SEDATION FOR PEDIATRIC PATIENTS IN ORAL RESTORATION

Objective To evaluate the effect of midazolam alone on sedation in young children for dental restorative care. Methods Forty children, aged 5 to 10 years with a mean age of 7.3 years, participated in this study. Twenty-one patients were assigned to intervention group received 0. 5 mg/kg of oral midazolam 20 minutes prior to the beginning of dental treatment, and 19 patients in control group received placebo liquid 20 minutes before treatment. All patients received painless local anesthetic injection and were restrained with children＇s board and bands. Blood pressure （ BP）, heart rate （HR）, oxygen saturation, treatment compliance scores of the Ramsay scale, the Briekopf and Butmer scale, Frankl scale, and the Houpt scale were recorded. Each procedure was taped and all the data were evaluated every 5 minutes by an anesthetist or experienced dentist who was unaware of the drug given to the child. Results HR in intervention group （82. 5 ± 5.1 bpm） was much lower than that in control group （95.2 ± 8.9 bpm; F=31.20, P 〈0. 001 ）. Intervention group had a significantly lower systolic BP level （94.8±5.6 mmHg） than control group （98.5±5.5 mm Hg; F=4. 34, P =0. 04）, but the diastolic BP （63.0 ± 3.5 mm Hg） was not significantly lower than control group （ 65.5 ± 4. 8 mm Hg; F = 3.31, P = 0. 07 ）. Children in intervention group showed more compliance. The patients＇ scores of the Ramsay scale, Briekopf and Buttner scale, Frankl scale, and Houpt scale in intervention group （ 1.37 ± 0. 96, 1.37 ± 0. 83, 1.32 ± 0. 67, and 2. 32 ± 1.49, respectively） were significantly lower than those in control group （3.71 ± 1.23, 2.71 ± 0. 96, 2.71 ± 0. 90, and 4.71 ± 1.19 ; F = 44. 66, 22. 36, 30.39,and 31.88,respectively,all P〈0.001） Conclusions Oral midazolam alone is safe and produces effective sedation for the dental treatment of young children. Oral midazolam application should be generally preferred because it is more easily accepted by pediatric patients.

Oral administration of the herbal oligonucleotide XKC-sRNA-h3 prevents angiotensinⅡ-induced hypertension in mice

Hypertension has become a growing public health concern worldwide.In fact,hypertension is commonly associated with increased morbidity and mortality.Currently,oligonucleotide drugs have proven to be promising therapeutic agents for various diseases.In the present study,we aimed to demonstrate that a herbal small RNA(s RNA),XKC-sRNA-h3(B55710460,F221.I000082.B11),exhibits potent antihypertensive effects by targeting angiotensin-converting enzyme(ACE)in mice.When compared with captopril,oral administration of the sphingosine(d18:1)-XKC-s RNA-h3 bencaosome more effectively prevented angiotensin II-induced hypertensive cardiac damage and alleviated kidney injury in mice.Such findings indicated that XKC-sRNA-h3 may be a novel orally available ACE inhibitor type oligonucleotide drug for hypertension.

Pharmacokinetics of diclazuril after oral administration of clinical doses to rabbits

The purpose of this study was to evaluate the pharmacokinetic parameters and bioavailability of the solid dispersion formulation of diclazuril after oral administration in rabbits in comparison with its known premix form with feed additive.Plasma concentrations were determined by high-performance liquid chromatography（HPLC）.The areas under the plasma concentration curves（AUC0-∞） of diclazuril in solid dispersion and premix were 247.8±18.1μg/h/mL and 145.4±12.6μg/h/mL,respectively. The Cmax of diclazuril in solid dispersion and premix were 33.72±4.75 μg/mL and 10.42±3.4μg/mL, respectively, The t1/2 were 9.53±1.37 and 9.23±1.20 min, respectively. The oral bioavailability of drug solid dispersion was 1.7-fold higher than that of premix. From these data we concluded that diclazuril solid dispersion may be used as a potential anticoccidial preparation.

A practical method to trace intracellular and transcellular transport pathways of gold nanoparticles via oral administration

Oral nanoparticles play an important role in improving the bioavailability of poorly water-soluble drug. It is necessary to investigate the interaction of nanoparticles with intestinal epithelial cells. In general, nano-carriers labeled with fluorescent probes are always chosen. However, fluorescent dye via physical loading may leak in complex biological environment and lose its function to trace the transport behavior ofnanoparticles. Fluorescent probes chemically coupled on the nanoparticles may alter the properties of nanoparticles. Therefore, a facile and exact detection method is required to trace intracellular and transcellular pathways of oral nano-medicines. In our study, gold nanoparticles were selected as nano-carriers owing to their unique characteristics of light scattering. The feasibility of gold nanoparticle detection through reflected light signal was tested in different situations, including gold nanoparticle solution, cell and animal level As a result, high resolution image of gold nanoparticles could be detected through reflection mode by confocal laser scanning microscope （CLSM） when excited at a wavelength of 633 nm. The reflected light signal of gold nanoparticles could be clearly shown in different intestinal epithelial cells no matter when they were in fixed or in living state, and the intracellular trafficking and distribution of gold nanoparticles were clearly shown in three-dimensional image. Meanwhile, this method was also applied to rat small intestine in vivo. In conclusion, we believed that this technique was a convenient and precise way to explore the transport behavior of gold nanoparticles via oral administration without fluorescent dye.

Low-dose lipopolysaccharide as an immune regulator for homeostasis maintenance in the central nervous system through transformation to neuroprotective microglia

Microglia,which are tissue-resident macrophages in the brain,play a central role in the brain innate immunity and contribute to the maintenance of brain homeostasis.Lipopolysaccharide is a component of the outer membrane of gram-negative bacteria,and activates immune cells including microglia via Toll-like receptor 4 signaling.Lipopolysaccharide is generally known as an endotoxin,as administration of highdose lipopolysaccharide induces potent systemic inflammation.Also,it has long been recognized that lipopolysaccharide exacerbates neuroinflammation.In contrast,our study revealed that oral administration of lipopolysaccharide ameliorates Alzheimer’s disease pathology and suggested that neuroprotective microglia are involved in this phenomenon.Additionally,other recent studies have accumulated evidence demonstrating that controlled immune training with low-dose lipopolysaccharide prevents neuronal damage by transforming the microglia into a neuroprotective phenotype.Therefore,lipopolysaccharide may not a mere inflammatory inducer,but an immunomodulator that can lead to neuroprotective effects in the brain.In this review,we summarized current studies regarding neuroprotective microglia transformed by immune training with lipopolysaccharide.We state that microglia transformed by lipopolysaccharide preconditioning cannot simply be characterized by their general suppression of proinflammatory mediators and general promotion of anti-inflammatory mediators,but instead must be described by their complex profile comprising various molecules related to inflammatory regulation,phagocytosis,neuroprotection,anti-apoptosis,and antioxidation.In addition,microglial transformation seems to depend on the dose of lipopolysaccharide used during immune training.Immune training of neuroprotective microglia using lowdose lipopolysaccharide,especially through oral lipopolysaccharide administration,may represent an innovative prevention or treatment for neurological diseases;however more vigorous studies are still required to properly modulate these treatments.

Optimal dosing time of Dachengqi decoction for protection of extrapancreatic organs in rats with experimental acute pancreatitis

BACKGROUND Acute pancreatitis(AP)is a pancreatic inflammatory disorder that is commonly complicated by extrapancreatic organ dysfunction.Dachengqi decoction(DCQD)has a potential role in protecting the extrapancreatic organs,but the optimal oral administration time remains unclear.AIM To screen the appropriate oral administration time of DCQD for the protection of extrapancreatic organs based on the pharmacokinetics and pharmacodynamics of AP rats.METHODS This study consisted of two parts.In the first part,24 rats were divided into a sham-operated group and three model groups.The four groups were intragastrically administered with DCQD(10 g/kg)at 4 h,4 h,12 h,and 24 h postoperatively,respectively.Tail vein blood was taken at nine time points after administration,and then the rats were euthanized and the extrapancreatic organ tissues were immediately collected.Finally,the concentrations of the major DCQD components in all samples were detected.In the second part,84 rats were divided into a sham-operated group,as well as 4 h,12 h,and 24 h treatment groups and corresponding control groups(4 h,12 h,and 24 h control groups).Rats in the treatment groups were intragastrically administered with DCQD(10 g/kg)at 4 h,12 h,and 24 h postoperatively,respectively,and rats in the control groups were administered with normal saline at the same time points.Then,six rats from each group were euthanized at 4 h and 24 h after administration.Serum amylase and inflammatory mediators,and pathological scores of extrapancreatic organ tissues were evaluated.RESULTS For part one,the pharmacokinetic parameters(C max,T max,T 1/2,and AUC 0→t)of the major DCQD components and the tissue distribution of most DCQD components were better when administering DCQD at the later(12 h and 24 h)time points.For part two,delayed administration of DCQD resulted in lower IL-6 and amylase levels and relatively higher IL-10 levels,and pathological injury of extrapancreatic organ tissues was slightly less at 4 h after administration,while the results were similar between the treatment and corresponding control groups at 24 h after administration.CONCLUSION Delayed administration of DCQD might reduce pancreatic exocrine secretions and ameliorate pathological injury in the extrapancreatic organs of AP rats,demonstrating that the late time is the optimal dosing time.

Arsenic toxicity in mice and its possible amelioration

Oral administration of arsenic trioxide(3 and 6 mg/kg body weight/d) for 30 d caused, as compared with vehicle control, dose dependent significant reductions in body weight, absolute weight, protein, glycogen, as well as, total, dehydro and reduced ascorbic acid contents both in the liver and kidney of arsenic treated mice. Succinic dehydrogenase(SDH) and phosphorylase only in the liver activities were significantly reduced in a dose dependent manner. Acid phosphatase activity was significantly decreased in the liver of low dose arsenic treated animals; however, significant rise in its activity was observed in high dose group. As compared with vehicle control, treatment also caused significant dose dependent reductions in SDH, alkaline phosphatase and acid phosphatase activities in the kidney of mice. Vitamin E cotreatment as well as, 30 d withdrawal of arsenic trioxide treatment with or without vitamin E caused significant amelioration in arsenic induced toxicity in mice. Administration of vitamin E during withdrawal of treatment also caused significant amelioration as compared from only withdrawal of the treatment. It is concluded that vitamin E ameliorates arsenic induced toxicities in the liver and kidney of mice.

A meta-analysis of the efficacy of traditional Chinese medicine alone in the treatment of refractory gastroesophageal reflux disease

Background:To systematically evaluate the efficacy and safety of traditional Chinese medicine in the treatment of refractory gastroesophageal reflux.Methods:PubMed,The Cochrane Library,Embase,Web of Science,China National Knowledge Infrastructure,Wanfang Database,China Science and Technology Journal Database and Chinese BioMedical Literature Database were searched for randomized controlled trials of traditional Chinese medicine in the treatment of refractory gastroesophageal reflux from database establishment time to December 2020.After two researchers independently screened the literature,extracted data and evaluated the bias risk included in the study,RevMan5.3 software was used for meta-analysis.Results:A total of 12 randomized controlled trials,were included,including 893 patients.The results of meta-analysis showed that the total effective rate of the treatment group(relative risk=1.28,95%confidence interval(CI)(1.19,1.38),P<0.00001),RGERDQ(refractory gastroesophageal reflux disease)score(mean difference(MD)=−3.35,95%CI(−4.13,−2.57),P<0.00001],acid reflux(acid in the stomach comes out of the mouth)[MD=−0.30,95%CI(−0.45,−0.15),P<0.00001],heartburn(the feeling that the heart is burned)(MD=−0.44,95%CI(−0.60,−0.29),P<0.00001,and retrosternal pain(MD=−0.27,95%CI(−0.44,−0.10),P<0.00001,belching(MD=−0.40,95%CI(−0.57,−0.24),P<0.00001],endoscopic mucosal score(MD=−0.62,95%CI(−0.78,−0.46),P<0.00001],the differences were statistically significant,and the effective rate of mucosal improvement under endoscopy was P=0.93>0.05,with no statistically significant difference.Conclusion:The current evidence shows that traditional Chinese medicine in the treatment of refractory gastroesophageal reflux disease is better than that of western medicine in the total effective rate,relieving acid reflux,heartburn,retrosternal pain and belching symptoms,but it is impossible to judge the improvement of mucosa under endoscope.Due to the limitations of the quality and quantity of included studies,more high-quality studies are needed to confirm the above conclusions.

Microenvironment responsive pod-structured astaxanthin nanocarrier for ameliorating inflammatory bowel disease

Anti-inflammatory drugs targeting inflammatory bowel disease(IBD)have attracted considerable attention but still face low therapeutic outcomes and frequent side effects.Astaxanthin(ATX),a natural ketone,possesses potent antioxidant and anti-inflammatory properties.However,it faces problems such as poor water solubility,photothermal instability,and low bioavailability.Here,we employed a supramolecular encapsulation strategy to create a nanoscale oral delivery system for ATX(referred to as FC-ATX NPs)by coupling fucoidan(FUC)with chitosan oligosaccharides(COS).The obtained FC-ATX NPs exhibited a particular“bean pod”structure with uniform size,good encapsulation efficiency,excellent physical and chemical stability,pH-triggered intestinal targeted slow-release properties,and potent antioxidant capacity.In vitro cell culture experiments showed that FC-ATX NPs promoted cellular uptake and scavenged excessive intracellular reactive oxygen species(ROS).In mouse models of colitis,FC-ATX NPs enhanced the drug absorption of intestinal epithelial cells and effectively accumulated at the site of inflammation.This work provides an efficient approach to enhance the bioavailability of ATX and has excellent application potential as an oral targeted delivery system for colitis therapy.

Double-layer probiotic encapsulation for enhanced bacteriotherapy against inflammatory bowel disease

Inflammatory bowel disease(IBD)is inflammatory intestinal disorders associated with dysregulated gut microbiota.Bacteriotherapy that leverages bacteria as therapeutics has shown tremendous promise in resolving gut dysbiosis and reducing inflammatory mediators to treat IBD.Orally delivered probiotics,such as Escherichia coli Nissle 1917(EcN),can produce beneficial ingredients,competitively inhibit the proliferation of pathogens,and promote the restoration of gut microbiome homeostasis.However,environmental stresses(such as gastric acids)in the gastrointestinal(GI)tract pose an enormous challenge to the probiotics following oral administration,leading to decreases in viability and activity of probiotics.Meanwhile,the inferior mucoadhesive capability of probiotics results in low colonization efficacy,further compromising their therapeutic effect.Coating probiotics with functional biomaterials may protect them from elimination and prolong their retention in the GI tract.Here,we developed a facile double-layer electrostatic assembly technique to encapsulate EcN bacteria in protective layers of mucoadhesive chitosan(CS)and immunomodulatory hyaluronic acid(HA)to generate HA-CS-EcN.These biomaterials confer the coated EcN resistance to environmental assault and enhanced mucoadhesion in the GI tract.The probiotics equipped with the multifunctional shield can thus suppress inflammation and reshape the intestinal microenvironment to enhance therapeutic efficacy for the prevention and treatment of IBD.Collectively,this study presents a novel probiotic coating strategy to augment the outcome of bacteriotherapy to combat IBD.

Comparative pharmacokinetic studies of borneol in mouse plasma and brain by different administrations

Borneol,a monoterpenoid alcohol,is used widely,particularly in combined formulas for preventing and curing cardiovascular and cerebrovascular diseases in traditional Chinese medicine.In order to understand the blood and brain pharmacokinetics after intravenous,intranasal,or oral administration and to investigate the superiority and feasibility of intranasal administration,a simple gas chromatographic (GC) method with flame ionization detection (FID) was developed for the quantification of borneol.Blood samples and brain were collected from mice at 1,3,5,10,20,30,60,90,and 120 min after intravenous,intranasal,or oral administration of borneol at a dosage of 30.0 mg/kg.Sample preparations were carried out by liquid-liquid extraction with an internal standard solution of octadecane.The pharmacokinetic parameters were calculated by the software of Kinetica.The calibration curves were linear in the range of 0.11-84.24 μg/ml and 0.16-63.18 μg/g for borneol in plasma and brain,respectively.The methodological and extraction recoveries were both in the range of 85%-115%.The intra-day and inter-day variabilities for plasma and brain samples were ≤5.00% relative standard deviation (RSD).The absolute bioavailabilities F of intranasal and oral administrations were 90.68% and 42.99%.The relative brain targeted coefficients Re of intranasal and oral administrations were 68.37% and 38.40%.The GC-FID method developed could be applied to determination and pharmacokinetic study.The borneol from injection was distributed and metabolized fast without absorption process.The borneol from oral administration was distributed more slowly and had the lowest absolute bioavailability.Nasal administration of borneol was quickly absorbed into the blood and brain,was easy to use and had a greater safety than infection,which makes it worthy of further development as an administration route for encephalopathy treatment.