AAPS PharmSciTech最新文献

{"title":"Fabrication of Luteolin Nanoemulsion by Box-Behnken Design to Enhance its Oral Absorption Via Lymphatic Transport","authors":"Liangxing Tu,&nbsp;Ju Wang,&nbsp;Yongbing Sun,&nbsp;Yang Wan","doi":"10.1208/s12249-024-02898-4","DOIUrl":"10.1208/s12249-024-02898-4","url":null,"abstract":"<div><p>Intestinal lymphatic transport offers an alternative and effective way to deliver drugs, such as avoiding first-pass metabolism, enhancing oral bioavailability, and facilitating the treatment of targeted lymphoid-related diseases. However, the clinical use of luteolin (LUT) is limited by its poor water solubility and low bioavailability, and enhancing lymphatic transport by nanoemulsion may be an efficient way to enhance its oral bioavailability. The objective of this work is to prepare the luteolin nanoemulsions (LUT NEs), optimized its preparation parameters by using Box-Behnken design optimization (BBD) and evaluated it <i>in vitro</i> and <i>in vivo</i>. An Caco-2 / Raji B cell co-incubation monolayer model was established to simulate the M-cell pathway, and the differences in the transmembrane transport of LUT and NEs were compared. Cycloheximide (CHX) was utilized to establish rat chylomicron (CM) blocking model, and for investigating the influence of pharmacokinetic parameters in rats thereafter. The results showed that LUT NEs have good stability, the particle sizes were about 23.87 ± 0.57 nm. Compared with LUT suspension, The <i>P</i>_<i>app</i> of LUT NEs was enhanced for 3.5-folds, the oral bioavailability was increased by about 2.97-folds. In addition, after binding with chylomicron, the oral bioavailability of LUT NEs was decreased for about 30% (AUC _0–∞ (μg/L*h): 5.356 ± 1.144 <i>vs</i> 3.753 ± 0.188). These results demonstrated that NEs could enhance the oral absorption of luteolin via lymphatic transport routes.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"25 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142138869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Comparative Mathematical Analysis of Drug Release from Lipid-Based Nanoparticles","authors":"Pedram Porbaha,&nbsp;Ramin Ansari,&nbsp;Mohammad Reza Kiafar,&nbsp;Rahman Bashiry,&nbsp;Mohammad Mehdi Khazaei,&nbsp;Amirhossein Dadbakhsh,&nbsp;Amir Azadi","doi":"10.1208/s12249-024-02922-7","DOIUrl":"10.1208/s12249-024-02922-7","url":null,"abstract":"<div><p>Mathematical modeling of drug release from drug delivery systems is crucial for understanding and optimizing formulations. This research provides a comparative mathematical analysis of drug release from lipid-based nanoparticles. Drug release profiles from various types of lipid nanoparticles, including liposomes, nanostructured lipid carriers (NLCs), solid lipid nanoparticles (SLNs), and nano/micro-emulsions (NEMs/MEMs), were extracted from the literature and used to assess the suitability of eight conventional mathematical release models. For each dataset, several metrics were calculated, including the coefficient of determination (R²), adjusted R², the number of errors below certain thresholds (5%, 10%, 12%, and 20%), Akaike information criterion (AIC), regression sum square (RSS), regression mean square (RMS), residual sum of square (rSS), and residual mean square (rMS). The Korsmeyer-Peppas model ranked highest among the evaluated models, with the highest adjusted R² values of 0.95 for NLCs and 0.93 for other liposomal drug delivery systems. The Weibull model ranked second, with adjusted R² values of 0.92 for liposomal systems, 0.94 for SLNs, and 0.82 for NEMs/MEMs. Thus, these two models appear to be more effective in forecasting and characterizing the release of lipid nanoparticle drugs, potentially making them more suitable for upcoming research endeavors.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><img></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"25 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142138964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breaking Barriers in Alzheimer’s Disease: the Role of Advanced Drug Delivery Systems","authors":"Devank Shekho,&nbsp;Ritika Mishra,&nbsp;Raj Kamal,&nbsp;Rohit Bhatia,&nbsp;Ankit Awasthi","doi":"10.1208/s12249-024-02923-6","DOIUrl":"10.1208/s12249-024-02923-6","url":null,"abstract":"<div><p>Alzheimer’s disease (AD), characterized by cognitive impairment, brain plaques, and tangles, is a global health concern affecting millions. It involves the build-up of amyloid-β (Aβ) and tau proteins, the formation of neuritic plaques and neurofibrillary tangles, cholinergic system dysfunction, genetic variations, and mitochondrial dysfunction. Various signaling pathways and metabolic processes are implicated in AD, along with numerous biomarkers used for diagnosis, risk assessment, and research. Despite these, there is no cure or effective treatment for AD. It is critically important to address this immediately to develop novel drug delivery systems (NDDS) capable of targeting the brain and delivering therapeutic agents to modulate the pathological processes of AD. This review summarizes AD, its pathogenesis, related signaling pathways, biomarkers, conventional treatments, the need for NDDS, and their application in AD treatment. It also covers preclinical, clinical, and ongoing trials, patents, and marketed AD formulations.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"25 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142138965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design and Evaluation of Inorganic/Organic Hybrid Bio-composite for Site-Specific Oral Delivery of Darifenacin","authors":"Wafa Ishaq,&nbsp;Attia Afzal,&nbsp;Muhammad Farooq,&nbsp;Muhammad Sarfraz,&nbsp;Sherjeel Adnan,&nbsp;Hammad Ahmed,&nbsp;Muhammad Waqas,&nbsp;Zainab Safdar","doi":"10.1208/s12249-024-02916-5","DOIUrl":"10.1208/s12249-024-02916-5","url":null,"abstract":"<div><p>Benign hyperplasia (BHP) is a common disorder that affects men over the age of 60 years. Transurethral resection of the prostate (TURP) is the gold standard for operative treatment, but a range of drugs are also available to improve quality of life and to reduce BHP-associated urinary tract infections and complications. Darifenacin, an anti-muscarinic agent, has been found effective for relieving symptoms of overactive bladder associated with BHP, but the drug has poor solubility and bioavailability, which are major challenges in product development. An inorganic/organic bio-composite with gastric pH-resistant property was synthesized for the targeted oral delivery of Darifenacin to the lower gastrointestinal tract (GIT). This development was accomplished through co-precipitation of calcium carbonate in quince seed-based mucilage. The FTIR, XRD, DSC, and TGA results showed good drug-polymer compatibility, and the SEM images showed calcite formation in the quince hydrogel system. After 72 h, the drug release of 34% and 75% were observed in acidic (0.1N HCl) and 6.8 pH phosphate buffer, respectively. A restricted/less drug was permeated through gastric membrane (21.8%) as compared to permeation through intestinal membrane (65%.) The developed composite showed significant reduction in testosterone-induced prostatic hyperplasia (2.39 ± 0.12***) as compared to untreated diseased animal group. No sign of organ toxicity was observed against all the developed composites. In this study, we developed an inorganic–organic composite system that is highly biocompatible and effective for targeting the lower GIT, thereby avoiding the first-pass metabolism of darifenacin.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"25 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-024-02916-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142138966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral Bioavailability Enhancement of Poorly Soluble Drug by Amorphous Solid Dispersion Using Sucrose Acetate Isobutyrate","authors":"Eman M. Mohamed,&nbsp;Sathish Dharani,&nbsp;Tahir Khuroo,&nbsp;Mohammad T. H. Nutan,&nbsp;Phillip Cook,&nbsp;Rajendran Arunagiri,&nbsp;Mansoor A. Khan,&nbsp;Ziyaur Rahman","doi":"10.1208/s12249-024-02924-5","DOIUrl":"10.1208/s12249-024-02924-5","url":null,"abstract":"<div><p>The focus of the present work was to develop amorphous solid dispersion (ASD) formulation of aprepitant (APT) using sucrose acetate isobutyrate (SAIB) excipient, evaluate for physicochemical attributes, stability, and bioavailability, and compared with hydroxypropyl methylcellulose (HPMC) based formulation. Various formulations of APT were prepared by solvent evaporation method and characterized for physiochemical and <i>in-vivo</i> performance attributes such as dissolution, drug phase, stability, and bioavailability. X-ray powder diffraction indicated crystalline drug conversion into amorphous phase. Dissolution varied as a function of drug:SAIB:excipient proportion. The dissolution was more than 80% in the optimized formulation (F10) and comparable to HPMC based formulation (F13). Stability of F10 and F13 formulations stored at 25 C/60% and 40°C/75% RH for three months were comparable. Both ASD formulations (F10 and F13) were bioequivalent as indicated by the pharmacokinetic parameters C_max and AUC_0-∞. C_max and AUC_0-∞ of F10 and F13 formulations were 2.52 ± 0.39, and 2.74 ± 0.32 μg/ml, and 26.59 ± 0.39, and 24.79 ± 6.02 μg/ml.h, respectively. Furthermore, the bioavailability of ASD formulation was more than twofold of the formulation containing crystalline phase of the drug. In conclusion, stability and oral bioavailability of SAIB based ASD formulation is comparable to HPMC-based formulation of poorly soluble drugs.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"25 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142138870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a Stable Lyophilized Cyclophosphamide Monohydrate Formulation Using Non-Aqueous Solvents","authors":"Shaik Riyaz Ahammad,&nbsp;Damodharan Narayanasamy","doi":"10.1208/s12249-024-02920-9","DOIUrl":"10.1208/s12249-024-02920-9","url":null,"abstract":"<div><p>To ensure product stability, it is critical to maintain the monohydrate state of cyclophosphamide following lyophilization, as this is the most stable solid form of the Cyclophosphamide. On the other hand, because of their limited aqueous solubility and stability, non-aqueous solvents are preferred for determining the composition and stability of bulk solutions. Hence, the purpose of this study was to use non-aqueous solvents for determining the composition and stability of bulk solutions, and to shorten the lyophilization process by retaining the cyclophosphamide monohydrate. Furthermore, prior to selecting the solvent for the bulk solution consisting of 90:10 tertiary butyl alcohol (TBA) and acetonitrile (ACN), various factors were taken into account, including the freezing point, vapor pressure of solvents, solubility, and stability of cyclophosphamide monohydrate. The concentration of the bulk solution was adjusted to 200 mg/mL in order to optimize the fill volume, enhance sublimation rates at lower temperatures during primary drying, and eliminate the need for secondary drying. The differential scanning calorimetry (DSC) measurements of bulk solution were used to improve the lyophilization cycle. The lyophilization cycle opted was freezing at a temperature of -55 °C with annealing step at -22 °C by which the reconstitution time was significantly reduced. The drying was performed at below − 25 °C while maintaining a chamber pressure of 300 mTorr. The complete removal of non-aqueous solvents was achieved by retaining water within the system. The presence of cyclophosphamide monohydrate was confirmed using X-ray diffraction (XRD). The reduction of lyophilization process time was established by conducting mass transfer tests and evaluating the physicochemical properties of the pharmaceutical product. Using non-aqueous solvents for freeze-drying cyclophosphamide is a viable option, and this study provides significant knowledge for the advancement of future generic pharmaceuticals.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"25 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142091376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Dissolution, Solid-state Properties, and Long-term Storage Stability of Cryoprotectant-free Fenbendazole Nanoparticles","authors":"Giselle Bedogni,&nbsp;Lina Vargas Michelena,&nbsp;Katia Seremeta,&nbsp;Nora Okulik,&nbsp;Claudio Salomon","doi":"10.1208/s12249-024-02921-8","DOIUrl":"10.1208/s12249-024-02921-8","url":null,"abstract":"<div><p>Fenbendazole is an antiparasitic drug widely used in veterinary medicine to treat parasitic infections caused in animals like cattle, horses, sheep, and dogs. Recently, it has been repositioned as a potential alternative for cancer treatment. However, it is a highly hydrophobic molecule (0.9 ug/mL), which can compromise its dissolution rate and absorption. Thus, this work aimed to apply a nanotechnological approach to improve drug solubility and dissolution performance. Fenbendazole nanoparticles stabilized by different poloxamers were obtained by lyophilization without cryoprotectants. The behavior of the drug in the solid state was analyzed by X-ray diffractometry, differential scanning calorimetry, and infrared spectroscopy. The nanosystems were also evaluated for solubility and dissolution rate. A long-term stability evaluation was performed for three years at room temperature. The yields of the lyophilization ranged between 75 and 81% for each lot. The nanoparticles showed a submicron size (&lt; 340 nm) and a low polydispersity depending on the stabilizer. The physicochemical properties of the prepared systems indicated a remarkable amorphization of the drug, which influenced its solubility and dissolution performance. The drug dissolution from both the fresh and aged nanosystems was significantly higher than that of the raw drug. In particular, nanoparticles prepared with poloxamer 407 showed no significant modifications in their particle size in three years of storage. Physical stability studies indicated that the obtained systems prepared with P188, P237, and P407 suffered certain recrystallization during long storage at 25 °C. These findings confirm that selected poloxamers exhibited an important effect in formulating fenbendazole nanosystems with improved dissolution.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"25 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142091377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gastroretentive Delivery Approach to Address pH-Dependent Degradation of (+)- and (-)-Phenserine","authors":"Pratishtha Verma,&nbsp;Leyla Rezaei,&nbsp;Ramprakash Govindarajan,&nbsp;Nigel H. Greig,&nbsp;Maureen D. Donovan","doi":"10.1208/s12249-024-02903-w","DOIUrl":"10.1208/s12249-024-02903-w","url":null,"abstract":"<div><p>(-)-Phenserine (“phenserine”) and (+)-phenserine (posiphen; buntanetap) are longer-acting enantiomeric analogs of physostigmine with demonstrated promise in the treatment of Alzheimer’s and Parkinson’s diseases. Both enantiomers have short plasma half-lives, and their pharmacokinetics might be improved through the use of either once or twice-daily administration of an extended-release dosage form. Phenserine was observed to form a colored degradation product in near-neutral and alkaline pH environments, and at pH 7, the half-life of posiphen was determined to be ~ 9 h (40 °C). To limit luminal degradation which would reduce bioavailability, a gastroretentive tablet composed of a polyethylene oxide-xanthan gum matrix was developed. When placed in simulated gastric fluid (pH 1.2), approximately 70% of the phenserine was released over a 12 h period, and no degradants were detected in the release medium. In comparison, a traditional hydrophilic-matrix, extended-release tablet showed measurable amounts of phenserine degradation in a pH 7.2 medium over an 8 h release interval. These results confirm that a gastroretentive tablet can reduce the luminal degradation of phenserine or posiphen by limiting exposure to neutral pH conditions while providing sustained release of the drug over at least 12 h. Additional advantages of the gastroretentive tablet include reduced gastric and intestinal concentrations of the drug resulting from the slower release from the gastroretentive tablet which may also limit the occurrence of the dose-limiting GI side effects previously observed with immediate-release phenserine capsules.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"25 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbicidal Polymer Nanoparticles Containing Clotrimazole for Treatment of Vulvovaginal Candidiasis","authors":"María del Rocío Lara-Sánchez,&nbsp;Adriana Ganem-Rondero,&nbsp;María Guadalupe Nava-Arzaluz,&nbsp;Andrea Angela Becerril-Osnaya,&nbsp;Laura Abril Pérez-Carranza,&nbsp;Sergio Alcalá-Alcalá,&nbsp;Néstor Mendoza-Muñoz,&nbsp;Elizabeth Piñón-Segundo","doi":"10.1208/s12249-024-02914-7","DOIUrl":"10.1208/s12249-024-02914-7","url":null,"abstract":"<div><p>Vulvovaginal candidiasis (VVC) alters the innate cervicovaginal immunity, which provides an important barrier against viruses and other infections. The incidence of this disease has not decreased in the last 30 years, so effective treatments are still needed. Nanoparticles (NPs) of cellulose acetate phthalate (CAP) and clotrimazole (CLZ) were prepared by the emulsification-diffusion method. NPs were characterized using dynamic light scattering, atomic force microscopy and differential scanning calorimetry; their release profile was determined by the dialysis bag technique and mucoadhesion was evaluated with the mucin-particle method. The growth inhibition study of <i>Candida albicans</i> was carried out using the plate counting technique. Finally, accelerated physical stability tests of NPs were carried out, both in water and in SVF. The CAP-CLZ NPs had an average diameter of 273.4 nm, a PDI of 0.284, smooth surfaces and spherical shapes. <i>In vitro</i> release of CLZ from the CAP NPs was categorized with the Weibull model as a matrix system in which initial release was rapid and subsequently sustained. The inhibition of <i>C. albicans</i> growth by the CAP-CLZ NPs was greater than that of free CLZ, and the CAP-only NPs had a microbicidal effect on <i>C. albicans</i>. The NPs showed poor mucoadhesiveness, which could lead to studies of their mucopenetration capacities. An accelerated physical stability test revealed the erosion of CAP in aqueous media. A nanoparticulate system was developed and provided sustained release of CLZ, and it combined an antifungal agent with a microbial polymer that exhibited antifungal activity against <i>C. albicans</i>.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"25 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-024-02914-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142034901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isolation, Purification of Phenolic Glycoside 1 from Moringa oleifera Seeds and Formulation of Its Liposome Delivery System","authors":"Feng Shi,&nbsp;Mingjie Gong,&nbsp;Michael Adu-Frimpong,&nbsp;Xia Jiang,&nbsp;Xiaowen Wang,&nbsp;Qinyang Hua,&nbsp;Tingyuan Li,&nbsp;Jiaying Li,&nbsp;Jiangnan Yu,&nbsp;Elmurat Toreniyazov,&nbsp;Xia Cao,&nbsp;Qilong Wang,&nbsp;Ximing Xu","doi":"10.1208/s12249-024-02911-w","DOIUrl":"10.1208/s12249-024-02911-w","url":null,"abstract":"<div><p>In this study, N, N '-bis {4- [(α-L- rhamnosyloxy) benzyl]} thiourea (PG-1), a phenolic glycoside compound was purified from Moringa seed. The PG-1 has attracted extensive attention due to its anti-cancer, antioxidant, anti-inflammatory and hypoglycemic properties. However, some of its physicochemical properties such as oral bioavailability has not been studied. Herein, a highly purified PG-1 was extracted and incorporated in multiple layered liposomes (PG-1-L) to avoid its burst release and enhance oral bioavailability. After appropriate characterization, it was discovered that the obtained PG-1-L was stable, homogeneous and well dispersed with the average particle size being 89.26 ± 0.23 nm. Importantly, the <i>in vitro</i> release and <i>in vivo</i> oral bioavailability of PG-1-L were significantly improved compared with PG-1. In addition, MTT results showed that compared with the free PG-1, PG-1-L displayed obvious inhibitory effect on the HepG2 cells, while the inhibitory effect on healthy non-malignant 3T6 and LO-2 cells was not significant, indicating that PG-1-L had high safety. In conclusion, PG-1-L can be used as a promising delivery system and an ideal novel approach to improve the oral bioavailability and anticancer activity of PG-1.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"25 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142034874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}