Hesperidin and its aglycone hesperetin in breast cancer therapy: A review of recent developments and future prospects

Breast cancer (BC) has high incidence and mortality rates, making it a major global health issue. BC treatment has been challenging due to the presence of drug resistance and the limited availability of therapeutic options for triple-negative and metastatic BC, thereby urging the exploration of more effective anti-cancer agents. Hesperidin and its aglycone hesperetin, two flavonoids from citrus species, have been extensively evaluated for their anti-cancer potentials. In this review, available literatures on the chemotherapeutic and chemosensitising activities of hesperidin and hesperetin in preclinical BC models are reported. The safety and bioavailability of hesperidin and hesperetin as well as the strategies to enhance their bioavailability are also discussed. Overall, hesperidin and hesperetin can inhibit cell proliferation, migration and BC stem cells as well as induce apoptosis and cell cycle arrest in vitro. They can also inhibit tumour growth, metastasis and neoplastic changes in tissue architecture in vivo. Moreover, the co-administration of hesperidin or hesperetin with doxorubicin, letrozole or tamoxifen can enhance the efficacies of these clinically available agents. These chemotherapeutic and chemosensitising activities of hesperidin and hesperetin have been linked to several mechanisms, including the modulation of signalling pathways, glucose uptake, enzymes, miRNA expression, oxidative status, cell cycle regulatory proteins, tumour suppressor p53, plasma and liver lipid profiles as well as DNA repair mechanisms. However, poor water solubility, extensive phase II metabolism and apical efflux have posed limitations to the bioavailability of hesperidin and hesperetin. Various strategies for bioavailability enhancement have been studied, including the utilisation of nano-based drug delivery systems and the co-administration of hesperetin with other flavonoids. In particular, nanoformulated hesperidin and hesperetin possess greater chemotherapeutic and chemosensitising activities than free compounds. Despite promising preclinical results, further safety and efficacy evaluation of hesperidin and hesperetin as well as their nanoformulations in clinical trials is required to ascertain their potentials to be developed as clinically useful agents for BC treatment.     

Chitosan-based delivery systems for curcumin: A review of pharmacodynamic and pharmacokinetic aspects

Effective drug delivery is one of the most important issues associated with the administration of therapeutic agents that have low oral bioavailability. Curcumin is an active ingredient in the turmeric plant, which has low oral bioavailability due to its poor aqueous solubility. One strategy that has been considered for enhancing the aqueous solubility, and, thus, its oral bioavailability, is the use of chitosan as a carrier for curcumin. Chitosan is a biodegradable and biocompatible polymer that is relatively water-soluble. Therefore, various studies have sought to improve the aqueous solubility of chitosan. The use of different pharmaceutical excipients and formulation strategies has the potential to improve aqueous solubility, formulation processing, and the overall delivery of hydrophobic drugs. This review focuses on various methods utilized for chitosan-based delivery of curcumin.     

<Emphasis Type="Italic">In Vitro</Emphasis> and <Emphasis Type="Italic">Ex Vivo</Emphasis> Evaluations of Lipid Anti-Cancer Nanoformulations: Insights and Assessment of Bioavailability Enhancement

Lipid-based nanoformulations have been extensively investigated for improving oral efficacy of plethora of drugs. Chemotherapeutic agents remain a preferred option for effective management of cancer; however, most chemotherapeutic agents suffer from limitation of poor oral bioavailability that is associated with their physicochemical properties. Drug delivery via lipid-based nanosystems possesses strong rational and potential for improving oral bioavailability of such anti-cancer molecules through various mechanisms, viz. improving their gut solubilisation owing to micellization, improving mucosal permeation, improving lymphatic uptake, inhibiting intestinal metabolism and/or inhibiting P-glycoprotein efflux of molecules in the gastrointestinal tract. Various in vitro characterization techniques have been reported in literature that aid in getting insights into mechanisms of lipid-based nanodevices in improving oral efficacy of anti-cancer drugs. The review focuses on different characterization techniques that can be employed for evaluation of lipid-based nanosystems and their role in effective anti-cancer drug delivery.     

Improvement of anti-inflammatory and anti-angiogenic activity of berberine by novel rapid dissolving nanoemulsifying technique

Berberine, an isoquinoline alkaloid, has wide biological and pharmacological actions. Despite the promising pharmacological effects and safety of berberine, poor oral absorption due to its extremely low aqueous solubility results in poor oral systemic bioavailability. This limits its clinical usage. This study describes the development and characterization of self-nanoemulsifying drug delivery system (SNEDDS) of berberine in liquid as well as solid form with improved solubility, dissolution and in vivo therapeutic efficacy. The SNEDDS of berberine were prepared using Acrysol K-150, Capmul MCM and polyethylene glycol 400. The formulations were characterized for various in vitro physicochemical characteristics. In vivo efficacy was evaluated in acetic acid induced inflammatory bowel model in rats. Anti-angiogenic activity of the developed SNEDDS of berberine was studied using chick chorioallantoic membrane assay. SNEDDS of berberine rapidly formed nanoemulsions with globule size of 17–45 nm. The in vitro rate and extent of release of berberine from SNEDDS was significantly higher than berberine alone. Chick chorioallantoic membrane assay revealed potent anti-angiogenic activity of SNEDDS of berberine. These studies demonstrate that the SNEDDS of berberine is a promising strategy for improving its therapeutic efficacy and have potential application in the treatment of chronic inflammatory conditions and cancer.     

Characterization of Albendazole-Randomly Methylated-β-Cyclodextrin Inclusion Complex and In Vivo Evaluation of Its Antihelmitic Activity in a Murine Model of Trichinellosis

Albendazole is a benzimidazole carbamate extensively used in oral chemotherapy against intestinal parasites, due to its broad spectrum activity, good tolerance and low cost. However, the drug has the disadvantage of poor bioavailability due to its very low solubility in water; as a consequence, a very active area of research focuses on the development of new pharmaceutical formulations to increase its solubility, dissolution rate, and bioavailability. The primary objective of this study was to prepare randomly methylated β-cyclodextrins inclusion complexes to increase albendazole dissolution rate, in order to enhance its antiparasitic activity. This formulation therapeutic efficacy was contrasted with that of the pure drug by treating Trichinella spiralis infected mice during the intestinal phase of the parasite cycle, on days five and six post-infection. This protocol significantly decreased muscle larval burden measured in the parenteral stage on day 30 post-infection, when compared with the untreated control. Thus, it could be demonstrated that the inclusion complexes improve the in vivo therapeutic activity of albendazole.     

Albendazole Microcrystal Formulations Based on Chitosan and Cellulose Derivatives: Physicochemical Characterization and <Emphasis Type="Italic">In Vitro</Emphasis> Parasiticidal Activity in <Emphasis Type="Italic">Trichinella spiralis</Emphasis> Adult Worms

The oral route has notable advantages to administering dosage forms. One of the most important questions to solve is the poor solubility of most drugs which produces low bioavailability and delivery problems, a major challenge for the pharmaceutical industry. Albendazole is a benzimidazole carbamate extensively used in oral chemotherapy against intestinal parasites, due to its extended spectrum activity and low cost. Nevertheless, the main disadvantage is the poor bioavailability due to its very low solubility in water. The main objective of this study was to prepare microcrystal formulations by the bottom-up technology to increase albendazole dissolution rate, in order to enhance its antiparasitic activity. Thus, 20 novel microstructures based on chitosan, cellulose derivatives, and poloxamer as a surfactant were produced and characterized by their physicochemical properties and in vitro biological activity. To determine the significance of type and concentration of polymer, and presence or absence of surfactant in the crystals, the variables area under the curve, albendazole microcrystal solubility, and drug released (%) at 30 min were analyzed with a three-way ANOVA. This analysis indicated that the microcrystals made with hydroxyethylcellulose or chitosan appear to be the best options to optimize oral absorption of the active pharmaceutical ingredient. The in vitro evaluation of anthelmintic activity on adult forms of Trichinella spiralis identified system S10A as the most effective, of choice for testing therapeutic efficacy in vivo.     

Polymeric nanoparticle-encapsulated curcumin ("nanocurcumin"): a novel strategy for human cancer therapy

Background  

Curcumin, a yellow polyphenol extracted from the rhizome of turmeric (Curcuma longa), has potent anti-cancer properties as demonstrated in a plethora of human cancer cell line and animal carcinogenesis models. Nevertheless, widespread clinical application of this relatively efficacious agent in cancer and other diseases has been limited due to poor aqueous solubility, and consequently, minimal systemic bioavailability. Nanoparticle-based drug delivery approaches have the potential for rendering hydrophobic agents like curcumin dispersible in aqueous media, thus circumventing the pitfalls of poor solubility.     

Nanocrystal technology for improving therapeutic efficacy of flavonoids

BackgroundBioflavonoids, secondary metabolites of plants, are beneficial in regulating human physiological mechanisms. Bioflavonoids majorly exist in the dietary intake of fruits, vegetables, legumes, pulses, etc. In addition to their cardio-protective and neuroprotective activities, they also possess prominent pharmacological effects including anti-oxidant, anti-inflammatory, anti-proliferative and anti-thrombogenic actions. However, therapeutic efficacy of the bioflavonoids is hampered by their lipophilic nature, low solubility and variable bioavailability which catch the eyes of formulation scientists.PurposeNanocrystal formulations were studied for many bioflavonoids, although enough attention has not been given to their commercial exploitation, unlike drug nanocrystals. Nanocrystals of bioflavonoid can be prepared by top-down technique, bottom-up technique or combination of both. This review primarily focuses on nanocrystal technology for bioflavonoids, methods of production, critical process parameters, in vitro and in vivo studies conducted to evaluate the efficiency.MethodThe detailed literature survey was systematically carried out using different electronic databases. It includes Scopus, Web of Science, Medline via PubMed, EMBASE, and Google Scholar. Also up-to-date patent search was conducted to understand the prior art and available intellectual properties.Result and conclusionIt was observed that several formulation and process parameters have an impact on flavonoids nanocrystals and their therapeutic efficacy. Also, clinical studies of flavonoid nanocrystals are barely done so far and thus, substantial safety and efficacy data is necessary for its commercial applications. Nevertheless, nanocrystals can be explored as a promising technology platform for improving overall therapeutic performance of flavonoids in future.     

Development of a More Efficient Albumin-Based Delivery System for Gambogic Acid with Low Toxicity for Lung Cancer Therapy

Gambogic acid (GA) has been proven to be a potent chemotherapeutic agent for the treatment of lung cancer in clinical trials. However, GA is limited in its therapeutic value by properties such as poor water solubility and low chemical stability. In clinical trials, cationic arginine (Arg) was added to solubilize GA, and this may also cause other side effects. Here, we have designed and developed a more efficient human serum albumin (HSA)-based delivery system for GA with low toxicity which helps improve its solubility, chemical stability and increases its antitumor efficacy. The GA-HSA nanoparticles (NPs) were prepared by albumin-bound (nab^TM) technology, with a particle size of 135.2?±?35.03 nm, a zeta potential of ?21.81?±?1.24 mV, and a high entrapment efficiency. Compared with GA-Arg solution, the physical and chemical stability of the NPs were improved when stored at pH 7.4 in PBS or freeze-dried. The in vitro drug release showed that GA-HSA NPs had a more sustained release than GA-Arg solution. Furthermore, HSA NPs improved the therapeutic efficacy of GA and were less toxic compared with GA-Arg solution in A549-bearing mice. Therefore, this delivery system is a promising polymeric carrier for GA when used for tumor therapy.     

Silymarin: an insight to its formulation and analytical prospects

Silymarin, a potential phytochemical compound obtained from the seeds of Silybum marianum plant has been used as a hepatoprotective agent for more than a decade. So far, eight active components of silymarin flavonolignans have been identified, among which silibinin has been proven the most active. However, it had poor oral bioavailability due to extensive phase II metabolism, low permeability across intestinal epithelial cells, low aqueous solubility, and rapid excretion in bile and urine. Therefore it becomes necessary to understand all its formulation and analytical aspects from past to present, including all of its possible future prospects. In modern research scenario, nanotization strategies of drugs has served as a potential approach to enhance solubility, bioavailability and to develop a robust formulation. Several approaches have been utilized previously to enhance the solubility and bioavailability of silymarin to provide it a robust strength against physical, chemical, and environmental degradation. Nanoscale formulations such as nanoemulsion, nanosuspension, liposomes, and solid–lipid nanoparticles can be used to enhance solubility and to target them to desired cells with minimum harm to normal cells. However, many other approaches exist such as dendrimers, ceramic nanoparticles, and carbon nanotubes, which serve as a great vehicle in drug delivery to transport medicament at target sites. Therefore, the purpose of this review was to develop a better understanding of the problems associated with silymarin and approaches to overcome the difficulties to develop a better and stable formulation for food and pharmaceutical applications.     

Liposomal nanocarriers for statins: A pharmacokinetic and pharmacodynamics appraisal

Statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, are a well-known class of drug with beneficial therapeutic effects in cardiovascular disease and lipid disorders and have potential use against cancer. However, the bioavailability of statins is hampered due to low aqueous solubility and rapid metabolism. To improve pharmacokinetic profiles of statins, development of drug delivery systems is promising. Hence, the use of liposomes for selective delivery of statins to a selected site or for bioavailability enhancement is an effective strategy to increase statin therapeutic effects. Moreover, liposomal delivery can reduce the required dose of statins especially in terms of antitumor effects. Liposomes, because of their unique properties and biphasic and amphiphilic nature, have attracted much interest and can be considered as a suitable choice for delivery of both hydrophilic and lipophilic statins. In this review article, we focus on liposomes and evaluate the effects of different liposomal delivery systems, based on differences in size, phospholipid composition, circulation half-life, and cholesterol content, on statin function.     

Recent advances in chemistry,therapeutic properties and sources of polydatin

Polydatin (PLD), the 3-O-β-glucopyranoside of the well-known stilbenoid compound resveratrol, is a major compound of Fallopia japonica (Houtt.) R. Decr. (Japanese knotweed), which is widely used in traditional Chinese medicine to treat infection, inflammatory diseases and circulatory problems. It has shown a wide range of biological activities including anti-inflammatory, anti-oxidant, anti-cancer, neuroprotective, hepatoprotective, nephroprotective and immunostimulatory effects. Although resveratrol has similar beneficial effects, its low bioavailability has remained a problem. Glycosylation increases solubility of resveratrol in an aqueous environment, thus improving its bioavailability. This has led to a growing interest in PLD. Promising results obtained from bioactivity studies have boosted an intense research on this compound. The aim of this review is to give a comprehensive overview of the botanical sources, pharmacology, biosynthesis, biotechnological production, and bioactivities of PLD, and to discuss clinical studies on this compound.     

Dual role of autophagy for advancements from conventional to new delivery systems in cancer

Autophagy, a programmed cell-lysis mechanism, holds significant promise in the prevention and treatment of a wide range of conditions, including cancer, Alzheimer's, and Parkinson's disease. The successful utilization of autophagy modulation for therapeutic purposes hinges upon accurately determining the role of autophagy in disease progression, whether it acts as a cytotoxic or cytoprotective factor. This critical knowledge empowers scientists to effectively manipulate tumor sensitivity to anti-cancer therapies through autophagy modulation, while also circumventing drug resistance. However, conventional therapies face limitations such as low bioavailability, poor solubility, and a lack of controlled release mechanisms, hindering their clinical applicability. In this regard, innovative nanoplatforms including organic and inorganic systems have emerged as promising solutions to offer stimuli-responsive, theranostic-controlled drug delivery systems with active targeting and improved solubility. The review article explores a variety of organic nanoplatforms, such as lipid-based, polymer-based, and DNA-based systems, which incorporate autophagy-inhibiting drugs like hydroxychloroquine. By inhibiting the glycolytic pathway and depriving cells of essential nutrients, these platforms exhibit tumor-suppressive effects in advanced forms of cancer such as leukemia, colon cancer, and glioblastoma. Furthermore, metal-based, metal-oxide-based, silica-based, and quantum dot-based nanoplatforms selectively induce autophagy in tumors, leading to extensive cancer cell destruction. Additionally, this article discusses the current clinical status of autophagy-modulating drugs for cancer therapy with valuable insights of progress and potential of such approaches.     

Synthesis and evaluation of a paclitaxel-binding polymeric micelle for efficient breast cancer therapy

Paclitaxel(PTX) is one of the most effective anticancer drugs for the treatment of various solid tumors, but its clinical use is limited by its poor solubility, low bioavailability, and severe systemic toxicity. Encapsulation of PTX in polymeric nanoparticles is used to overcome these problems but these micelles still need improvements in stability, pharmacokinetics, therapeutic efficacy, and safety profiles. In this study, we demonstrate a facile fabrication of a stable PTX-binding micelle made from poly(ethylene glycol)-block-dendritic polylysine, whose primary amines were reacted with phenethyl isothiocyanate(PEITC), a hydrophobic anticancer agent under clinical study. The amphiphilic conjugate(PEG-Gx-PEITC; Gx, the generation of the polylysine dendron) formed well-defined micelles whose core was composed of phenyl groups and thiourea groups binding PTX via π-π stacking and hydrogen bonding. Compared with the PTX-loaded poly(ethylene glycol)-block-poly(D,L-lactide)(PEGPDLLA/PTX) micelles in clinical use, PTX-loaded PEG-Gx-PEITC third-generation(PEG-G3-PEITC/PTX) micelles showed slowed blood clearance, enhanced tumor accumulation, and thus much improved in vivo therapeutic efficacy in both subcutaneous and orthotopic human breast cancer xenografts. Therefore, PEG-G3-PEITC is a promising drug delivery system for PTX in the treatment of breast cancer.     

Antiproliferative activity of long chain acylated esters of quercetin-3-O-glucoside in hepatocellular carcinoma HepG2 cells

Despite their strong role in human health, poor bioavailability of flavonoids limits their biological effects in vivo. Enzymatically catalyzed acylation of fatty acids to flavonoids is one of the approaches of increasing cellular permeability and hence, biological activities. In this study, six long chain fatty acid esters of quercetin-3-O-glucoside (Q3G) acylated enzymatically and were used for determining their antiproliferative action in hepatocellular carcinoma cells (HepG2) in comparison to precursor compounds and two chemotherapy drugs (Sorafenib and Cisplatin). Fatty acid esters of Q3G showed significant inhibition of HepG2 cell proliferation by 85 to 90% after 6 h and 24 h of treatment, respectively. The cell death due to these novel compounds was associated with cell-cycle arrest in S-phase and apoptosis observed by DNA fragmentation, fluorescent microscopy and elevated caspase-3 activity and strong DNA topoisomerase II inhibition. Interestingly, Q3G esters showed significantly low toxicity to normal liver cells than Sorafenib (P < 0.05), a chemotherapy drug for hepatocellular carcinoma. Among all, oleic acid ester of Q3G displayed the greatest antiproliferation action and a high potential as an anti-cancer therapeutic. Overall, the results of the study suggest strong antiproliferative action of these novel food-derived compounds in treatment of cancer.     

Recombinant GDNF: Tetanus toxin fragment C fusion protein produced from insect cells

Glial cell line-derived neurotrophic factor (GDNF) has potent survival-promoting effects on CNS motor neurons in experimental animals. Its therapeutic efficacy in humans, however, may have been limited by poor bioavailability to the brain and spinal cord. With a view toward improving delivery of GDNF to CNS motor neurons in vivo, we generated a recombinant fusion protein comprised of rat GDNF linked to the non-toxic, neuron-binding fragment of tetanus toxin. Recombinant GDNF:TTC produced from insect cells was a soluble homodimer like wild-type GDNF and was bi-functional with respect to GDNF and TTC activity. Like recombinant rat GDNF, the fusion protein increased levels of immunoreactive phosphoAkt in treated NB41A3-hGFRα-1 neuroblastoma cells. Like TTC, GDNF:TTC bound to immobilized ganglioside GT1b in vitro with high affinity and selectivity. These results support further testing of recombinant GDNF:TTC as a non-viral vector to improve delivery of GDNF to brain and spinal cord in vivo.     

Development and Evaluation of Avanafil Self-nanoemulsifying Drug Delivery System with Rapid Onset of Action and Enhanced Bioavailability

Utilization of lipid-based drug delivery systems has recently gained focus for drugs characterized by poor aqueous solubility. The improved aqueous solubility overcomes one of the main barriers that limit their bioavailability. The objective of this work was to improve the solubility and oral bioavailability of Avanafil (AVA), a recently approved second generation type 5 phospodiesterase inhibitor used for erectile dysfunction.AVA was formulated as self-nanoemulsifying drug delivery system (SNEDDS) utilizing various oils, surfactants, and cosurfactants. The solubility of AVA in various oils, surfactants, and cosurfactants was determined. Ternary phase diagram was constructed to identify stable nanoemulsion region. The prepared AVA loaded SNEDDS were assessed for optical clarity, droplet size, conductivity, and stability studies. In vitro drug release and in vivo pharmacokinetic parameters using animal model were also investigated. Results revealed that stable AVA (SNEDDS) were successfully developed with a droplet size range of 65 to 190 nm. SNEDDS composed of 25% dill oil, 55% Tween 80, and 20% propylene glycol successfully improved solubilization of AVA (over 80% within 30 min) vis-a-vis the powder AVA (35% within 30 min). In vivo pharmacokinetic showed a significant (P < 0.05) increase in C_max, reduction in T_max, and SNEDDS enhanced the bioavailability in the rats by 1.4-fold when compared with pure drug.Key words: avanafil, erectile dysfunction, dill oil, self-nanoemulsifying, SNEDDS     

Biogenic nanoporous silicon carrier improves the efficacy of buparvaquone against resistant visceral leishmaniasis

Visceral leishmaniasis is a vector-borne protozoan infection that is fatal if untreated. There is no vaccination against the disease, and the current chemotherapeutic agents are ineffective due to increased resistance and severe side effects. Buparvaquone is a potential drug against the leishmaniases, but it is highly hydrophobic resulting in poor bioavailability and low therapeutic efficacy. Herein, we loaded the drug into silicon nanoparticles produced from barley husk, which is an agricultural residue and widely available. The buparvaquone-loaded nanoparticles were several times more selective to kill the intracellular parasites being non-toxic to macrophages compared to the pure buparvaquone and other conventionally used anti-leishmanial agents. Furthermore, the in vivo results revealed that the intraperitoneally injected buparvaquone-loaded nanoparticles suppressed the parasite burden close to 100%. By contrast, pure buparvaquone suppressed the burden only by 50% with corresponding doses. As the conclusion, the biogenic silicon nanoparticles are promising carriers to significantly improve the therapeutic efficacy and selectivity of buparvaquone against resistant visceral leishmaniasis opening a new avenue for low-cost treatment against this neglected tropical disease threatening especially the poor people in developing nations.     

Targeted delivery of quercetin loaded mesoporous silica nanoparticles to the breast cancer cells

BackgroundMesoporous silica nanoparticles (MSNs) have been promising vehicles for drug delivery. Quercetin (Q), a natural flavonoid, has been reported to have many useful effects. However, poor water solubility as well as less bioavailability has confined its use as a suitable anti-cancer drug. Therefore, profound approach is required to overcome these drawbacks.MethodsWe have synthesized folic acid (FA) armed mesoporous silica nanoparticles (MSN-FA-Q) loaded with quercetin and then characterized it by DLS, SEM, TEM and FTIR. MTT, confocal microscopy, flow cytometry, scratch assay and immunoblotting were employed to assess the cell viability, cellular uptake, cell cycle arrest, apoptosis, wound healing and the expression levels of different signalling molecules in breast adenocarcinoma cells. Nanoparticle distribution was investigated by using ex vivo optical imaging and CAM assay was employed to assess tumor regression.ResultsMSN-FA-Q facilitates higher cellular uptake and allows more drug bioavailability to the breast cancer cells with over-expressed folate receptors. Our experimental results suggest that the newly synthesized MSN-FA-Q nanostructure caused cell cycle arrest and apoptosis in breast cancer cells through the regulation of Akt & Bax signalling pathways. Besides, we also observed that MSN-FA-Q has a concurrent anti-migratory role as well.ConclusionThis uniquely engineered quercetin loaded mesoporous silica nanoparticle ensures a targeted delivery with enhanced bioavailability.General significanceEffective targeted therapeutic strategy against breast cancer cells.     

A Self-microemulsifying Drug Delivery System (SMEDDS) for a Novel Medicative Compound Against Depression: a Preparation and Bioavailability Study in Rats

AJS is the code name of an untitled novel medicative compound synthesized by the Tasly Holding Group Company (Tianjin, China) based on the structure of cinnamamide, which is one of the Biopharmaceutics Classification System (BCS) class II drugs. The drug has better antidepressant effect, achieved by acting on the 5-hydroxytryptamine receptor. However, the therapeutic effects of the drug are compromised due to its poor water solubility and lower bioavailability. Herein, a self-microemulsifying drug delivery system (SMEDDS) was developed to improve its solubility and oral bioavailability. AJS-SMEDDS formulation was optimized in terms of drug solubility in the excipients, droplet size, stability, and drug precipitation using a pseudo-ternary diagram. The pharmacokinetic study was performed in rats, and the drug concentration in plasma samples was assayed using the high-performance liquid chromatography-electrospray tandem mass spectrometry (HPLC-MS/MS) method. The optimized formulation for SMEDDS has a composition of castor oil 24.5%, Labrasol 28.6%, Cremphor EL 40.8%, and Transcutol HP 2.7% (co-surfactant). No drug precipitation or phase separation was observed from the optimized formulation after 3 months of storing at 25°C. The droplet size of microemulsion formed by the optimized formulation was 26.08 ± 1.68 nm, and the zeta potential was −2.76 mV. The oral bioavailability of AJS-SMEDDS was increased by 3.4- and 35.9-fold, respectively, compared with the solid dispersion and cyclodextrin inclusion; meanwhile, the C_max of AJS-SMEDDS was about 2- and 40-fold as great as the two controls, respectively. In summary, the present SMEDDS enhanced oral bioavailability of AJS and was a promising strategy to orally deliver the drug.KEY WORDS: bioavailability, HPLC-MS/MS, self-microemulsifying drug delivery system, solubilization, stability