Route Of Drug Delivery Research Articles

Nasal drug delivery for Chronic Rhinosinusitis: An Overview

Nasal delivery is the logical choice for topical treatment of local diseases in the nose and Paranasal sinuses such as allergic and non-allergic rhinitis and sinusitis. The nose is also considered an attractive route for needle-free vaccination and for systemic drug delivery, especially when rapid absorption and effect are desired. In addition, nasal delivery may help address issues related to poor bioavailability, slow absorption, drug degradation, and adverse events in the gastrointestinal tract and avoids the first-pass metabolism in the liver. However, when considering nasal delivery devices and mechanisms, it is important to keep in mind that the prime purpose of the nasal airway is to protect the delicate lungs from hazardous exposures, not to serve as a delivery route for drugs and vaccines. The narrow nasal valve and the complex convoluted nasal geometry with its dynamic cyclic physiological changes provide efficient filtration and conditioning of the inspired air, enhance olfaction, and optimize gas exchange and fluid retention during exhalation. However, the potential hurdles these functional features impose on efficient nasal drug delivery are often ignored. With this background, the advantages and limitations of existing and emerging nasal delivery devices and dispersion technologies are reviewed with focus on their clinical performance. The role and limitations of the in vitro testing in the FDA guidance for nasal spray pumps and pressurized aerosols (pressurized metered-dose inhalers) with local action are discussed. Moreover, the predictive value and clinical utility of nasal cast studies and computer simulations of nasal airflow and deposition with computer fluid dynamics software are briefly discussed. New and emerging delivery technologies and devices with emphasis on BiDirectional™ delivery, Keywords Drug delivery Nasal Device Paranasal sinuses Topical Systemic Vaccine Nasal valve Particle deposition Clearance

Formulation of Wound Healing Transdermal Patch from Tubers Extract of Momordica Cymbalaria and its In-vitro Evaluation

Developing wound infection in type Ⅰ or Ⅱ diabetic people had risk complications like gangrene. Although there are enough antibiotic ointments or creams, still it needs physician dressing and continuous monitoring of wound. So, to make it simple and more effective, a combination of transdermal drug delivery route with herbal usage contribute in controlled release of medication with minimum undesirable side effects. And also help to treat wound infections by self-medication. This work is focused, to formulate wound healing transdermal patch for diabetics with Momordica cymbalaria tuber extract. A sequence of techniques was performed to analyse antioxidant content then Starch assay was performed In vitro to evaluate its healing efficacy, determine cytotoxicity using zebra fish embryos and artemia salina using hexane extract of tuber. Optimized combination is used to prepare Patch by solvent evaporation method then evaluated the patch by organoleptic and physico-chemical properties. The result proofs, the tuber extract had Strong Antioxidant activity whereas weak cytotoxicity showed in two concentration (25 and 50µg/ml) towards brine shrimp lethality assay and fish embryo toxicity. High migration rate found in 25µg/ml and 50µg/ml in scratch assay using Human Epidermal Keratinocytes. Evaluated the patch for its organoleptic and physico-chemical properties, it shows good result. As a final observation of the study, bio compounds present in tuber extract proved to enhance wound healing and could pave way as alternate to the synthetic wound healing patches owing to its ecofriendly, economical and herbal nature be natural replacement to hasten wound healing especially in diabetic patients.

Is postauricular injection a systemic or a topical route for inner ear drug delivery?

The challenges associated with the blood-labyrinth barrier and unwanted systemic adverse effects severely impede the development of systemic drug administration for inner ear therapy. Previous studies have demonstrated that postauricular injection might be an alternative route for the systemic administration for inner ear therapy because it is minimally invasive and can achieve a high drug concentration in the inner ear. However, the in vivo effects remain unclear. This study aimed to compare differences in cisplatin-induced ototoxicity and systemic adverse effects between postauricular and systemic administration. Here, we compared the differences in hair cell loss, body weight change, and renal dysfunction (indicated by serum levels of blood urea nitrogen and creatinine) between these two routes of administration. The results showed that although postauricular injection of cisplatin might induce greater hair cell damage in the ipsilateral cochleae than that after intraperitoneal injection, significant hair cell damage in the contralateral cochleae as well as systemic adverse effects were also observed. Our results indicated that: (1) topical administration effects might occur in the ipsilateral inner ear following postauricular injection, and (2) systemic circulation might also be an underestimated route of drug delivery to the inner ear following postauricular injection. Overall, postauricular injection is a hybrid administration route, which simultaneously shares the features of topical and systemic administration for inner ear drug delivery.

Routes of drug delivery

Routes of drug delivery

Recent Advances in Oral Mucoadhesive Drug Delivery.

The oral cavity is one of the most important routes for local and systemic drug delivery, as it has a large surface, high permeability, and rich blood supply. Oral mucosal drug delivery has some advantages, such as enhancing bioavailability, preventing first-pass metabolism, reducing dose frequency, and non-invasiveness. In recent years, notable oral mucoadhesive patents were introduced to the pharmaceutical field, which indicates promising potentials for therapeutic purposes. Oral mucosal drug delivery can play a key role to deliver the biological drugs, such as antimicrobial peptides. This article gives an overview of oral mucoadhesive drug delivery systems and provides basic principles for the researchers to overcome the problems associated with the formulation design.

Lipid-Based Nanocarriers for Oral Delivery of Proteins and Peptides: Opportunities, Challenges, and Future Prospects

Oral administration is the most common drug delivery route with high levels of patient acceptance. However, oral delivery of therapeutic proteins/peptides is extremely difficult, and improving the pharmacological bioavailability still is a challenging goal because of the poor membrane permeability, high molecular weight, and enzymatic degradation of these drugs. Lipid-based nanocarriers represent a viable means for enhancing the oral bioavailability of protein or peptide drugs while minimizing toxicity. Nowadays, like other macromolecules protein or peptide drugs are the promising candidates to be delivered employing liposomes and lipid nanoparticles including solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC). Generally, these drug delivery strategies can reduce protein or peptide drug degradation and improve membrane permeability thus enhance bioavailability. This review demonstrates various lipid-based formulation strategies used for successful oral delivery of peptides and proteins, assesses the hurdles and delivery efficiency and their clinical implications. Dhaka Univ. J. Pharm. Sci. 20(3): 395-416, 2022 (June) Centennial Special Issue

Development of a three-dimensional blood-brain barrier network with opening capillary structures for drug transport screening assays.

The blood-brain barrier (BBB), a selective barrier regulating the active and passive transport of solutes in the extracellular fluid of the central nervous system, prevents the delivery of therapeutics for brain disorders. The BBB is composed of brain microvascular endothelial cells (BMEC), pericytes and astrocytes. Current in vitro BBB models cannot reproduce the human structural complexity of the brain microvasculature, and thus their functions are not enough for drug assessments. In this study, we developed a 3D self-assembled microvascular network formed by BMEC covered by pericytes and astrocyte end feet. It exhibited perfusable microvasculature due to the presence of capillary opening ends on the bottom of the hydrogel. It also demonstrated size-selective permeation of different molecular weights of fluorescent-labeled dextran, as similarly reported for in vivo rodent brain, suggesting the same permeability with actual in vivo brain. The activity of P-glycoprotein efflux pump was confirmed using the substrate Rhodamine 123. Finally, the functionality of the receptor-mediated transcytosis, one of the main routes for drug delivery of large molecules into the brain, could be validated using transferrin receptor (TfR) with confocal imaging, competition assays and permeability assays. Efficient permeability coefficient (Pe) value of transportable anti-TfR antibody (MEM-189) was seven-fold higher than those of isotype antibody (IgG1) and low transportable anti-TfR antibody (13E4), suggesting a higher TfR transport function than previous reports. The BBB model with capillary openings could thus be a valuable tool for the screening of therapeutics that can be transported across the BBB, including those using TfR-mediated transport.

Synthesis, Molecular Docking and ADME-TOX Studies of New Tacrine Analogs as Promising for Alzheimer's Disease Therapy

Abstract: The modification of drug delivery routes can be used as a promising strategy to improve the therapeutic profile of various drug agents. Herein, the synthesis and molecular modeling of a series of 6,7,8,9-tetrahydrobenzo [b] [1,8] naphthyridines derivatives were reported to explore potent and less toxic scaffolds. The tacrine analogs 6–10 were obtained by an efficient strategy using Friedlander's condensation between 2-aminopyridine-3-carbonitriles 1–5 and cyclohexanone under microwave irradiations without catalysts and solvents. The synthesized compounds were identified through 1H NMR, 13C NMR, IR. Their inhibition activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) were focused as probable drug targets for Alzheimer’s disease (AD). The pharmaco-kinetic properties, the risk of probable hepato-toxic metabolites, and the toxicological properties were predicted using computational methods. The prediction of the toxicity risks via the GUSAR software allowed us to resolve the best approach for drug delivery, namely the subcutaneous, intravenous, or oral route., Also, the GUSAR software was used to reveal all possible adverse effects. All these techniques were tested for the L1-6 compounds by choosing tacrine as a template compound. Among these compounds, the optimal compound L1 was the most potent inhibitor and had the best score binding affinity compared to the reference drug (Tacrine) -7.926 and -7.007 kcal/mol for AChE and BuChE, respectively. Moreover, this same compound presented a satisfying pharmaceutical profile. In the present study, subcutaneous delivery is considered a promising administration of reference drug and their derivatives against AD.

Newer advances in medical management of glaucoma.

The burden of irreversible vision loss from Glaucoma continues to rise. While the disease pathogenesis is not well understood, intraocular pressure (IOP) is the only modifiable risk factor identified to prevent glaucomatous vision loss. Medical management remains the first-line of treatment in most adult glaucomas and the evolution of medical therapy for glaucoma has followed an exponential curve. This review tracks the rapid development of new medications and drug delivery systems in the recent years. Introduction of Rho kinase inhibitors with an entirely new mechanism of action from that of the currently used anti glaucoma medications has been a significant milestone. Latanoprostene Bunod is a novel, single molecule which provides two active metabolites that work through two different pathways for reducing intra ocular pressure. Bimatoprost implants and travoprost punctum plugs attempt to ease chronic medication use in glaucoma patients. Nanotechnology is an evolving route of drug delivery. Role of cannabinoids in medical management of glaucoma remain equivocal. The relatively short term effect on IOP, the risks of developing tolerance and side effects impacting patients’ neurocognitive health greatly outweigh the potential benefit. Research on Latrunculin B, Adenosine receptor agonists, Specific gene silencing and Stem cell therapy are poised to make an impact on glaucoma treatment. While there is some evidence to support the role of Brimonidine in neuroprotection, further research is needed to clarify the role of Memantine and Neurotrophins. Evidence for benefit from dietary supplementation with Alpha lipoic acid, Forskolin , and Ginko Biloba is limited

Different Methods and Formulations of Drugs and Vaccines for Nasal Administration.

Nasal drug delivery is advantageous when compared with other routes of drug delivery as it avoids the hepatic first-pass effect, blood–brain barrier penetration, and compliance issues with parenteral administration. However, nasal administration also has some limitations, such as its low bioavailability due to metabolism on the mucosal surface, and irreversible damage to the nasal mucosa due to the ingredients added into the formula. Moreover, the method of nasal administration is not applicable to all drugs. The current review presents the nasal anatomy and mucosal environment for the nasal delivery of vaccines and drugs, as well as presents various methods for enhancing nasal absorption, and different drug carriers and delivery devices to improve nasal drug delivery. It also presents future prospects on the nasal drug delivery of vaccines and drugs.

Antioxidant activity and phytochemical constituents of Philippine Clitoria ternatea flowers as a potential therapeutic agent against infectious diseases

Infectious diseases have always been present throughout human history, in which numerous emerging and re-emerging pathogens have been documented. Various strategies have been established to combat these pathogens: from vaccinations, to optimized drug delivery routes, to natural products such as antioxidants and flavonoids. This study evaluated the antioxidant activity of the ethanolic extract of the anthocyanin-rich Clitoria ternatea flowers, from the Philippines, by analyzing its total phenolic content and DPPH radical scavenging activity. The raw materials used in this study were collected from Victoria, Tarlac, Philippines, which are then macerated and soaked in 95% ethanol for 24 hours before extraction. The extract was then filtered using coarse filter paper and concentrated using a rotary evaporator. The samples were subjected to heavy metals analysis, Total phenolic content and IC50 from DPPH radical scavenging activity of the C. ternatea extract were found to be 3.9519 ± 0.1 mg GAE / 100 g and 53.6913 mg/kg, respectively. Phytochemical screening of the ethanolic extract of C. ternatea revealed the presence of triterpenes, saponins, reducing sugars, tannins, sterols, flavonoids, and alkaloids. Results show the potent antioxidant properties and the abundance of flavonoids of C. ternatea extract which may encourage further studies to evaluate its possible applications as plant-derived antioxidants for the therapeutic management of various infectious diseases. Keywords: Antioxidant activity, DPPH radical scavenging activity, phytochemical constituents, Clitoria ternatea

Acute exercise in 5‐Fluorouracil cardiotoxicity: Effects on cardiac function and reverse phase protein analysis

Background5‐Fluorouracil (5FU) is a commonly administered chemotherapeutic agent used in the treatment of numerous cancers. Though efficacious in treatment of malignancies, 5FU is associated with dose limiting cardiotoxicity that often necessitates deviation from preferred treatment regimens and increases reliance on other, less effective treatment alternatives. The mechanisms driving these toxicities are poorly understood, but leading theories include direct myocardial damage and coronary vasospasm. Data to support these theories have historically been derived from pre‐clinical animal models utilizing i.p injection of 5FU rather than protocols designed to mimic the drug delivery route utilized in clinical practice (i.v. infusion). Further, others have demonstrated the effectiveness of acute exercise in prevention of cardiotoxicity induced by other chemotherapies, however there are no studies evaluating the efficacy of exercise in prevention of 5FU cardiotoxicity.Purpose & HypothesisThe present investigation assessed the effect of 4 moderate intensity treadmill running bouts prior to administration of a clinically relevant dose of 5FU on the functional cardiovascular wellbeing of rats. We tested the hypotheses that a 2‐hr infusion of 5FU would reduce echocardiographic measures of ejection fraction (EF) and fractional shortening (%FS) compared to a saline infusion, and that completion of an acute exercise protocol prior to 5FU treatment would mitigate these cardiotoxic effects.MethodsMale Sprague‐Dawley rats were randomized to receive 5FU (n=15) or saline (CON, n=11) via a 50 mg/kg jugular bolus followed by a 2‐hr 265 mg/kg continuous infusion. A subset of each group (n=7 ex5FU, n=4 exCON) completed 4 bouts of moderate intensity treadmill running (25 min each) commencing 3 days prior to 5FU/saline treatment with the final run ending 1‐hr prior to treatment onset. The remaining animals acted as sedentary controls (n=7 s5FU, n=8 sCON). Echocardiographic variables were compared between groups at baseline and 2‐hr time points (mixed‐model design). Reverse phase protein analysis (RPPA) was conducted on cardiac tissue excised immediately following completion of the infusion for insight into molecular alterations induced by 5FU and/or exercise.ResultsEF at 2‐hr was reduced in sCON (92±2 vs 86±3%, P=.01), s5FU (91±2 vs 86±2%, P=.03), and ex5FU (87±2 vs 82±1%, P=.02), but not in exCON (91±2 vs 87±1%, P=.35) with no timepoint differences between groups (P=0.23). Similarly, %FS decreased from baseline to 2‐hr in sCON (60±3 vs 52±4%, P=.00), s5FU (59±3 vs 51±3%, P=.03), and ex5FU (53±3 vs 45±1%, P=.04), but not in exCON (58±4 vs 52±1, P=.28) with no differences between groups at either time point (P=0.97). RPAA analysis identified graded key changes in CAV‐1, SMAD, and BCL2L1.ConclusionThe present findings suggest small reductions in EF and %FS following completion of a 2‐hr infusion of 5FU or saline, with no differences between the treatments. Further, reductions in EF and %FS were mitigated by prior exercise in exCON, but not in ex5FU. Future work will place emphasis on quantifying the molecular changes indicated by RPPA to better understand alterations induced by 5FU within the heart at the cellular level.

Salvianolic acid B dry powder inhaler for the treatment of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a serious and fatal pulmonary inflammatory disease with an increasing incidence worldwide. The drugs nintedanib and pirfenidone, are listed as conditionally recommended drugs in the “Evidence-Based Guidelines for the Diagnosis and Treatment of Idiopathic Pulmonary Fibrosis”. However, these two drugs have many adverse reactions in clinical application. Salvianolic acid B (Sal B), a water-soluble component of Salvia miltiorrhiza, could alleviate bleomycin-induced peroxidative stress damage, and prevent or delay the onset of IPF by regulating inflammatory factors and fibrotic cytokines during the disease's progression. However, Sal B is poorly absorbed orally, and patient compliance is poor when administered intravenously. Therefore, there is an urgent need to find a new non-injection route of drug delivery. In this study, Sal B was used as model drug and l-leucine (LL) as excipient to prepare Sal B dry powder inhaler (Sal B-DPI) by spray drying method. Modern preparation evaluation methods were used to assess the quality of Sal B-DPI. Sal B-DPI is promising for the treatment of IPF, according to studies on pulmonary irritation evaluation, in vivo and in vitro pharmacodynamics, metabolomics, pharmacokinetics, and lung tissue distribution.

The role of intrinsic fines in the performance change of expired lactose carriers for DPI applications

Dry powder inhalation offers a well-established administration route for either local or systemic drug delivery. Lactose-based powder blends still build the basis of respiratory drug delivery, despite of numerous emerging formulation approaches. The amount of fine lactose excipients, either extrinsic or intrinsic, crucially influences the aerodynamic performance of the corresponding blend. This study highlights the role of intrinsic fines as a fundamental performance affecting parameter during storage and expiry of lactose carrier bulk. We showed that intrinsic fines play an inferior role after expiring compared to fresh batches. If strongly adhering or even merged fines regain their mobility and contribute to the dispersion (by removal and re-addition), it will significantly enhance drug delivery. Furthermore, we provide evidence for decreased mobility of intrinsic fines caused by humidity (e.g., during inappropriate storage) resulting in decreased powder fluidisation.

Dermal Lymphatic Capillaries Do Not Obey Murray's Law.

Lymphatic vessels serve as a major conduit for the transport of interstitial fluid, immune cells, lipids and drugs. Therefore, increased knowledge about their development and function is relevant to clinical issues ranging from chronic inflammation and edema, to cancer metastasis to targeted drug delivery. Murray's Law is a widely-applied branching rule upheld in diverse circulatory systems including leaf venation, sponge canals, and various human organs for optimal fluid transport. Considering the unique and diverse functions of lymphatic fluid transport, we specifically address the branching of developing lymphatic capillaries, and the flow of lymph through these vessels. Using an empirically-generated dataset from wild type and genetic lymphatic insufficiency mouse models we confirmed that branching blood capillaries consistently follow Murray's Law. However surprisingly, we found that the optimization law for lymphatic vessels follows a different pattern, namely a Murray's Law exponent of ~1.45. In this case, the daughter vessels are smaller relative to the parent than would be predicted by the hypothesized radius-cubed law for impermeable vessels. By implementing a computational fluid dynamics model, we further examined the extent to which the assumptions of Murray's Law were violated. We found that the flow profiles were predominantly parabolic and reasonably followed the assumptions of Murray's Law. These data suggest an alternate hypothesis for optimization of the branching structure of the lymphatic system, which may have bearing on the unique physiological functions of lymphatics compared to the blood vascular system. Thus, it may be the case that the lymphatic branching structure is optimized to enhance lymph mixing, particle exchange, or immune cell transport, which are particularly germane to the use of lymphatics as drug delivery routes.

Novel approaches of gastro retentive drug delivery system

Oral route of drug administration is the most convenient route and accepted route of drug delivery. It is probable that at least 90% of all the drugs given by oral route. There are different drug deliveries to cure the diseases through oral route. Among them Gastroretentive drug delivery system plays an important and significant role in novel drug delivery systems. The floating systems, bioadhesive drug delivery system, expandable drug delivery system, high density systems, effervescent systems (Gas Generating systems), non-effervescent systems etc are various approaches. The wide applications can be achieved through this delivery system are enhanced bioavailability, sustained drug delivery, site-specific drug delivery, absorption enhancement, mitigating adversity at colon etc. In addition to specified above, the advantages and disadvantages, drugs and polymers used and the method of evaluation is also summarized in this review.

Review of Anticoagulation in Continuous Renal Replacement Therapy.

Continuous renal replacement therapy is an important, yet challenging, treatment of critically ill patients with kidney dysfunction. Clotting within the dialysis filter or circuit leads to time off therapy and impaired delivery of prescribed treatment. Anticoagulation can be used to prevent this complication; however, doing so introduces risk for unintended complications such as bleeding or metabolic derangements in patients who are already critically ill. A thorough understanding of indications, therapeutic options, and monitoring principles is necessary for safe and effective use of this strategy. This review provides clinicians important information regarding when to anticoagulate, differences in pharmacologic agents, recommended doses, routes of drug delivery, and appropriate laboratory monitoring for patients receiving anticoagulation to support continuous renal replacement therapy.

Advances and Challenges in Intranasal Delivery of Antipsychotic Agents Targeting the Central Nervous System.

Treatment of central nervous system (CNS) disorders is challenging using conventional delivery strategies and routes of administration because of the presence of the blood–brain barrier (BBB). This BBB restricts the permeation of most of the therapeutics targeting the brain because of its impervious characteristics. Thus, the challenges of delivering the therapeutic agents across the BBB to the brain overcoming the issue of insufficient entry of neurotherapeutics require immediate attention for recovering from the issues by the use of modern platforms of drug delivery and novel routes of administration. Therefore, the advancement of drug delivery tools and delivering these tools using the intranasal route of drug administration have shown the potential of circumventing the BBB, thereby delivering the therapeutics to the brain at a significant concentration with minimal exposure to systemic circulation. These novel strategies could lead to improved efficacy of antipsychotic agents using several advanced drug delivery tools while delivered via the intranasal route. This review emphasized the present challenges of delivering the neurotherapeutics to the brain using conventional routes of administration and overcoming the issues by exploring the intranasal route of drug administration to deliver the therapeutics circumventing the biological barrier of the brain. An overview of different problems with corresponding solutions in administering therapeutics via the intranasal route with special emphasis on advanced drug delivery systems targeting to deliver CNS therapeutics has been focused. Furthermore, preclinical and clinical advancements on the delivery of antipsychotics using this intranasal route have also been emphasized.

Transdermal Drug Delivery System: An Overview

From the past three decades there are huge changes and developments in formulation technology. Innovations in drug delivery systems are not only associated with the development of novel dosage forms but also with the development of new formulations using existing drugs for the treatment. These innovations in delivery of drug have many advantages like better patient compliance, maintenance of steady state concentration of drug for the prolong period, reducing dosing frequency, drug targeting to desired site of action and low side effects. TDDS are designed for delivery of drugs across the skin and it provides both controlled and continuous administration drug. It terminates the pulsed entry of drug in systemic circulation due to which side effects are observed. This transdermal route of drug delivery has more benefits and convenience than oral route and enhances the safety and efficacy of drug; it is patient friendly and painless device that provides regulated, uniform administration and the continuous supply of drug to targeted site for treatment of various diseases.

Efficacy of Chinese herbal medicine for tPA thrombolysis in experimental stroke: A systematic review and meta-analysis

BackgroundTissue-type plasminogen activator (tPA) remains the sole FDA approved thrombolytic drug for ischemic stroke. But delayed thrombolytic therapy with tPA may increase the risk of hemorrhagic transformation. Many Chinese herbal medicines have been used as tPA helpers to enhance the capacity of tPA and minimize the risk of hemorrhagic transformation. The efficacy of Chinese herbal medicines on tPA thrombolysis is not systematically analyzed. MethodsWe searched the following three databases up to January 2022: Web of Science, PubMed, and Scopus. Studies that reported the efficacy and safety of Chinese herbal medicines on tPA thrombolysis in experimental stroke were included. The efficacy outcomes were neurological score and infarct volume, the safety outcomes were cerebral hemorrhage and blood brain barrier (BBB) damage. We used the checklist of CAMARADES to assess the quality of included studies. Standardized mean difference (SMD) with 95% confidence intervals were used to assess all the outcomes. Subgroup analyses were performed to explore the sources of heterogeneity. Trim and fill method and Egger's test were used to assess the potential publication bias. Sensitivity analyses were used to identify the stability of the results. ResultsA total of nine studies including 11 Chinese herbal medicines fulfilled the inclusion criteria and were subsequently analyzed. The pooled data demonstrated that Chinese herbal medicines improved neurological score (2.23 SMD, 1.42–3.04), infarct volume (1.08 SMD, 0.62–1.54), attenuated cerebral hemorrhage (1.87 SMD, 1.34–2.4), and BBB dysfunction (1.9 SMD, 1.35–2.45) following tPA thrombolysis in experimental stroke. Subgroup analysis indicated that the route of drug delivery, dosage of tPA, and stroke model used may be factors inducing heterogeneity and influencing the efficacy. ConclusionTreatment with Chinese herbal medicines significantly improved neurological score and infarct volume, reduced cerebral hemorrhage and BBB damage after tPA thrombolysis. This study supports Chinese herbal medicine as an adjuvant therapy in reducing the side effects of tPA thrombolysis after acute ischemic stroke. The results should be interpreted with more caution since this article was based on animal studies.