Journal of Pharmaceutical Innovation最新文献

{"title":"Utilizing Quality by Design to Develop and Evaluate Extended-Release Upadacitinib Tablets Incorporating a Biosynthesized Polymer","authors":"K. Sunil Chowdary,&nbsp;A. A. Napoleon","doi":"10.1007/s12247-023-09754-1","DOIUrl":"10.1007/s12247-023-09754-1","url":null,"abstract":"<div><h3>Objectives</h3><p>The aim of this study was to develop and optimize the production of upadacitinib extended-release tablets containing biosynthesized hydrophilic carriers and/or polymers in the core and coating. This was achieved by applying quality by design (QbD) approach and its built-in quality control aspects to adhere to the general principles of sustainability including subsistence, efficiency, and consistency during the product life cycle. Upadacitinib is an inhibitor of the Janus kinase class of enzymes. In this study, the characterization of the reference product, physicochemical parameters of the drug molecule, and the quality target product profile was considered along with critical attributes of quality to initiate drug development. Critical attributes related to material properties, process parameters, and the formulation variables were identified, and their preliminary level of risk was assessed. The factorial design of an experiment with three center points was achieved using Design Expert v12 to investigate the customary monolithic extended-release tablets of matrix formulation. In order to evaluate tablet performance, critical quality attributes (CQAs) were determined by dissolution tests. Finally, factors that can influence the formulation, including its compositions, manufacturing procedures, and analytical evaluation, were examined. The goal was to identify formulations that exhibit a similar release pattern through the entire 12-h dissolution testing period.</p><h3>Materials and Methods</h3><p>Various release rates of biosynthesized polymer-based upadacitinib extended-release formulations were compared to the reference product, Innovator (Rinvoq), using in vitro dissolution test. The selected “T-5” formulation was optimized and evaluated using the QbD method to satisfy the principles of sustainability throughout the product life cycle.</p><h3>Results</h3><p>All experimental upadacitinib tablet formulations demonstrated favorable drug release patterns, though not to the required extent. However, the “T-5” formulation released 80% of the drug within the required time.</p><h3>Conclusions</h3><p>The “T-5” formulation was considered suitable for the further development of extended-release tablets of upadacitinib, as it contained optimal amount of biosynthesized hydrophilic polymer.</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"18 4","pages":"1879 - 1891"},"PeriodicalIF":2.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48388919","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 Computational Approach for Exploring Indinavir as a Potent Protease Inhibitor and Development of Its Microsphere for Anticancer Activity","authors":"Prasanta Kumar Mohapatra,&nbsp;Rajnish Srivastava,&nbsp;Krishna Kumar Varshney,&nbsp;Sunit Kumar Sahoo,&nbsp;Asha Kesari","doi":"10.1007/s12247-023-09747-0","DOIUrl":"10.1007/s12247-023-09747-0","url":null,"abstract":"<div><h3>Purpose</h3><p>The objective of the present investigation was to establish a molecular association of different proteases as cancer targets with the indinavir and how the physicochemical characteristics of the indinavir sulfate microsphere vary with different process variables was systemically established.</p><h3>Methods</h3><p>Molecular interactions with indinavir were identified and established by molecular simulation docking studies. Indinavir sulfate-loaded microspheres were prepared by the oil-in-oil emulsion solvent evaporation technique.</p><h3>Results</h3><p>Results indicated that indinavir could interact with all four proteases at the active binding site of receptors. Indinavir was found to show significantly higher interaction with Matrix Metalloproteases, Aspartate Proteases, and Cysteine Proteases with a binding energy of -8.80, -8.19, and -6.87, respectively, as compared to their native ligand. However, serine proteases exhibit less but significant interaction with a binding energy of -5.92 than the native ligand. The microspheres exhibited 72%-93% of entrapment and prolonged drug release (DR), up to 9 h. The drug-loaded microspheres showed invariable character by the Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and thermographs and revealed no drug-polymer interactions. The decrease in the drug's crystallinity was observed in X-ray diffraction (XRD). The scanning electron microscope (SEM) study revealed the spherical and porous nature of microspheres.</p><h3>Conclusion</h3><p>Indinavir could act as a potential inhibitor of different proteases associated with tumor growth initiation, progression, and metastasis, and microspheres with sustained DR could be utilized to deliver an anticancer drug in a more targeted way as an emerging cancer microsphere technology.\u0000</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"18 4","pages":"1838 - 1869"},"PeriodicalIF":2.6,"publicationDate":"2023-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47695076","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 Delayed-Release Pellets of Ibuprofen Using Kollicoat® MAE 100P via Hot-Melt Extrusion Technology","authors":"Mittal Darji,&nbsp;Adwait Pradhan,&nbsp;Sateesh Kumar Vemula,&nbsp;K. Kolter,&nbsp;Nigel Langley,&nbsp;Michael A. Repka","doi":"10.1007/s12247-023-09758-x","DOIUrl":"10.1007/s12247-023-09758-x","url":null,"abstract":"<div><h3>Purpose</h3><p>The present work was intended to develop the ibuprofen-Kollicoat^® MAE 100P delayed-release pellets using hot-melt extrusion technology, which exhibits pH-dependent solubility. Ibuprofen irritates the gastric lining, so its release in the gastric environment is not desired. Conventionally, Kollicoat^® MAE 100P has been used as an enteric coating polymer, and we have explored its application using hot-melt extrusion technology in our work.</p><h3>Methods</h3><p>Three different drug loadings were processed at various extrusion temperatures using HME to produce pellets of uniform size. DSC was performed to study the drug’s state, the polymer’s thermal behavior, and drug-polymer miscibility. An in vitro drug release study was performed in 0.1N HCl followed by pH 6.8 phosphate buffer to understand the ability of the polymer to impede the release of ibuprofen in the stomach. Furthermore, the lead batch was characterized by DSC, FTIR, HS-PLM, and optical microscopy to study the interaction between the drug and polymer.</p><h3>Results</h3><p>The thermogram of the pellets indicated no drug-polymer immiscibility. This work also demonstrates proof of the plasticizing ability of ibuprofen. Drug release studies showed less than 1.5% drug release in 0.1N HCl in 2 h, and complete drug release was obtained in the next 2 h in pH 6.8 phosphate buffer, indicating the delayed-release characteristics of the pellets.</p><h3>Conclusion</h3><p>This work proves that Kollicoat^® MAE 100P could be used in modified-release dosage forms to attain the delayed-release pellets.</p><h3>Graphical Abstract</h3><p>Schematic representation of development of\u0000ibuprofen delayed release pellets</p>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"18 4","pages":"1827 - 1837"},"PeriodicalIF":2.6,"publicationDate":"2023-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46238856","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":"An Experimental Design Approach for Development of Crocin-Loaded Microparticles Embedded in Gelatin/Oxidized Alginate-Based Hydrogel","authors":"Faezeh Merati,&nbsp;Fatemeh Mehryab,&nbsp;Seyed Alireza Mortazavi,&nbsp;Azadeh Haeri","doi":"10.1007/s12247-023-09755-0","DOIUrl":"10.1007/s12247-023-09755-0","url":null,"abstract":"<div><h3>Purpose</h3><p>The objective of this study was to prepare gelatin/oxidized alginate (OAlg) hydrogel incorporating chitosan (CS)/alginate (Alg) microparticles (MPs) for topical delivery of crocin and maintaining MPs at the target site.</p><h3>Methods</h3><p>Crocin-loaded MPs were prepared using the ionic gelation method, and the effects of CS, Alg, and tripolyphosphate (TPP) concentrations on particle size and entrapment efficiency% (EE) were evaluated by applying a factorial design. OAlg was synthesized, and the optimum MP formulation was loaded into gelatin/OAlg hydrogel. The developed formulation was characterized in terms of morphology, chemical structure, crystallinity, thermal behavior, viscosity, swelling behavior, mucoadhesion, and in vitro release profile.</p><h3>Results</h3><p>The designed particles had a size ranging from 7.2 to 47.8 µm with the EE results varying between 12.5 and 58.4%. The mathematical models with suitable determination coefficients (<i>R</i>²) were established which confirmed a satisfactory correlation between the independent variables and the results. The optimized formulation showed a particle size of ~ 28 µm and a zeta potential of ~ 24 mV with about 58% crocin entrapment. The successful oxidation process was confirmed by the appearance of aldehyde peak in FTIR spectroscopy, and the oxidation degree (OD) of prepared OAlg was found to be about 62%. The prepared complex could release crocin in a sustained manner through 48 h and showed superior mucoadhesive strength, compared to gelatin/Alg-based hydrogel.</p><h3>Conclusion</h3><p>The fabricated gelatin/OAlg hydrogel containing CS/Alg MPs exhibited the promising potential to be utilized in mucosal delivery applications.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"18 4","pages":"1812 - 1826"},"PeriodicalIF":2.6,"publicationDate":"2023-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45771808","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":"Preparation, Optimization, and Evaluation of Dolutegravir Nanosuspension: In Vitro and In Vivo Characterization","authors":"Monika Bhairam,&nbsp;Ravindra Kumar Pandey,&nbsp;Shiv Shankar Shukla,&nbsp;Bina Gidwani","doi":"10.1007/s12247-023-09756-z","DOIUrl":"10.1007/s12247-023-09756-z","url":null,"abstract":"<div><h3>Purpose</h3><p>In this study, a nanosuspension of dolutegravir, an antiviral drug with solubility issues, was developed and optimized using a Design of Experiments (DoE) approach. The nanosuspension showed a significant improvement in drug dissolution compared to the pure drug.</p><h3>Methods</h3><p>The formulation process involved high-speed homogenization and probe sonication techniques, with Soluplus as the selected surfactant. The optimized nanosuspension demonstrated desirable pharmacokinetic profiles, surface morphology, and drug content. In vitro and in vivo studies confirmed the enhanced performance of the nanosuspension.</p><h3>Results</h3><p>The dolutegravir nanoparticles had a mean size of 337.1 nm, a low polydispersity index, and a negative zeta potential, indicating good stability. Experimental results in Wistar rats showed higher bioavailability for the nanosuspension compared to the pure drug, as evidenced by the increased AUC value. The optimized formulation exhibited improved in vitro drug release, increased solubility, and good stability. The sonication time played a crucial role in controlling the nanoparticle size. Further characterization using differential scanning calorimetry and X-ray diffraction confirmed the amorphous nature of the drug in the nanosuspension, explaining the enhanced solubility.</p><h3>Conclusion</h3><p>In conclusion, the nanosuspension approach offers a promising solution for improving the bioavailability of poorly soluble drugs like dolutegravir. The developed DGSD-Nanosuspension formulation shows potential for effectively treating HIV-positive individuals by enhancing drug absorption and therapeutic efficacy. This innovative approach holds promise for overcoming solubility challenges in HIV medication and may contribute to better treatment outcomes. Further research and clinical studies are needed to validate the effectiveness and safety of DGSD-Nanosuspension as a viable delivery system for dolutegravir and other poorly soluble drugs.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"18 4","pages":"1798 - 1811"},"PeriodicalIF":2.6,"publicationDate":"2023-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45606899","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":"Classification of Potent and Weak Penetration Enhancers Using Multiple Feature Selection Methods and Machine Learning Models","authors":"Baddipadige Raju,&nbsp;Neha Verma,&nbsp;Gera Narendra,&nbsp;Om Silakari,&nbsp;Bharti Sapra","doi":"10.1007/s12247-023-09757-y","DOIUrl":"10.1007/s12247-023-09757-y","url":null,"abstract":"<div><h3>Purpose</h3><p>Chemical penetration enhancers (CPEs) are important in transdermal drug delivery (TDDD) formulations because they assist drugs in moving across the stratum corneum. Hydrocortisone (0.1% hydrocortisone, propylene glycol), oestradiol (0.045 mg estradiol/0.015 mg levonorgestrel, propylene glycol), and testosterone (2% testosterone, propylene glycol) are some examples of marketing TDDD formulations. As the transdermal route for drug administration becomes a safer and more appealing alternative to hypodermic needles, the search for new CPEs and their development becomes more important. Thus, the current work was directed toward the rapid identification of potent CPEs through the development of robust machine learning (ML) classification models.</p><h3>Methods</h3><p>Two large penetration enhancer (PE) data sets reported to date such as hydrocortisone (139 PEs) and theophylline (101 PEs) were used to build classification models. In the present investigation, a combination of feature selection methods, i.e., Boruta and Recursive Feature Elimination (RFE), and machine learning (ML) algorithms such as support vector machine (SVM), random forest (RF), and artificial neural network (ANN) were employed to classify the potent and weak penetration enhancers of hydrocortisone and theophylline. The tenfold cross-validation and Y-randomization methods were used to evaluate the prediction performance of the developed models.</p><h3>Results</h3><p>Significant classification models were built for both data sets when the RFE method and RF algorithm were used. RF classifiers outperformed hydrocortisone and theophylline data sets with test set accuracy and Matthew’s correlation coefficient (MCC) greater than 0.78. Simultaneously, four important features required for the accurate classification of potent and weak PEs were identified, i.e., nHCsatu, minHCsatu, AATS4p, and GATS4e.</p><h3>Conclusion</h3><p>Our approach produced robust ML classification models that can be applied to prioritize PEs from large databases. Utilization of these ML models in virtual screening experiments could save time and effort in the identification of potential PEs.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"18 4","pages":"1778 - 1797"},"PeriodicalIF":2.6,"publicationDate":"2023-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47448718","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":"Novel Nanoaggregates from Phoenix dactylifera (date palm) for Inhalational Management of Cystic Fibrosis Using Dry Powder Inhalers","authors":"Hadeel Aburass,&nbsp;Nisreen Dahshan,&nbsp;Hamad Alyami,&nbsp;Affiong Iyire,&nbsp;Eman Zmaily Dahmash","doi":"10.1007/s12247-023-09752-3","DOIUrl":"10.1007/s12247-023-09752-3","url":null,"abstract":"<div><h3>Purpose</h3><p><i>Phoenix</i>\u0000<i>dactylifera</i> extracts have shown efficacy as antioxidants and antibacterials for the treatment of lung diseases; however, the choice of route of administration remains a problem. The use of natural antibacterial remedies for the management of cystic fibrosis (CF) is promising due to recurring bacterial resistance to current antibiotics. Dry powder inhalers (DPIs) have also been identified as a patient-friendly, noninvasive method for local delivery of drugs to the lungs. Therefore, this work, which is the first of its kind, aimed to formulate nanoparticles of date palm extracts as DPIs and evaluate their aerodynamic and antibacterial biofilm characteristics for the potential treatment of CF.</p><h3>Method</h3><p>Chitosan-based nanoparticles (CDN) comprising aqueous date fruit extract with increasing concentrations of chitosan (0.05, 0.1, and 0.2% w/v) were prepared. The in vitro aerosolization of the formulations was studied using a next-generation impactor (NGI), and good aerosolization profiles were achieved. The produced nanoparticles were characterized using FTIR and XRD to confirm physical properties and TEM and zeta sizer to confirm shape and size. The antimicrobial activity of CDN was evaluated using a <i>Pseudomonas aeruginosa</i> biofilm model cultured in an artificial sputum medium (ASM) mimicking cystic fibrosis conditions in the lungs.</p><h3>Results</h3><p>Nanoparticles containing 0.05% w/v chitosan demonstrated the highest encapsulation efficiency (55.91%) and delivered the highest emitted dose (98.92%) and fine particle fraction (42.62%). CDN demonstrated the first-time-ever reported significant 3.3 log-cycle inhibition of <i>P. aeruginosa</i> biofilm cultured in ASM. TEM images revealed the formation of spherical particles with an average size of 42.98 ± 19.19 nm. FTIR and XRD studies demonstrated the compatibility of the components with the presence of the characteristic features of chitosan and date powder.</p><h3>Conclusions</h3><p>This novel work showcases CDN as a prophylactic adjuvant for the management of cystic fibrosis using DPI.\u0000</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"18 4","pages":"1764 - 1777"},"PeriodicalIF":2.6,"publicationDate":"2023-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12247-023-09752-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48201947","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":"Blockchain for Data Originality in Pharma Manufacturing","authors":"Marta Durá,&nbsp;Fátima Leal,&nbsp;Ángel Sánchez-García,&nbsp;Carlos Sáez,&nbsp;Juan M. García-Gómez,&nbsp;Adriana E. Chis,&nbsp;Horacio González-Vélez","doi":"10.1007/s12247-023-09748-z","DOIUrl":"10.1007/s12247-023-09748-z","url":null,"abstract":"<div><h3>Purpose</h3><p>This paper analyses the feasibility of tracking data originality for pharmaceutical manufacturing in a tamper-proof manner using a geographically distributed system. The main research question is whether it is possible to ensure the traceability of drug manufacturing through the use of smart contracts and a private blockchain network.</p><h3>Methods</h3><p>This work employs a private Ethereum network with a proof-of-authority consensus algorithm to allow participating nodes to commit the medicament manufacturing originality as transactions in blocks. We use smart contracts to assess the “Original” principle of the ALCOA+ data integrity principles for full sensor-enabled production lines within pharmaceutical manufacturing plants. We have evaluated our data originality assessment approach employing a temporal series of 1300 reports generated based on real datasets from pharma production lines. Out of these reports, 300 reports have been randomly tampered with to make them “unoriginal” (i.e., falsified).</p><h3>Results</h3><p>Evaluation consistently shows that the proposed approach systematically detects all the manufacturing records whether original or not, together with any source of falsification. By randomly injecting four common data falsification types, their approach effectively detects tampering and ensures the authenticity of the data originality acquired by sensors within manufacturing lines.</p><h3>Conclusion</h3><p>The approach of using a private blockchain network with a proof-of-authority consensus algorithm and smart contracts is a feasible method to track data originality for pharmaceutical manufacturing in a tamper-proof manner. In addition, this approach effectively detects tampering and ensures the authenticity of the data originality acquired by sensors within manufacturing lines.</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"18 4","pages":"1745 - 1763"},"PeriodicalIF":2.6,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12247-023-09748-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44660129","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":"Development and Statistical Optimization of Polymer-Based Nanoparticulate Delivery System for Enhancing Cytarabine Efficacy in Leukemia Treatment","authors":"Nasrullah Jan,&nbsp;Asadullah Madni,&nbsp;Hassan Shah,&nbsp;Safiullah Khan,&nbsp;Qazi Amir Ijaz,&nbsp;Syed Faisal Badshah,&nbsp;Ahsan Ali,&nbsp;Umair Khurshid,&nbsp;Mohammad F. Bostanudin","doi":"10.1007/s12247-023-09753-2","DOIUrl":"10.1007/s12247-023-09753-2","url":null,"abstract":"<div><h3>Purpose</h3><p>Cytarabine, an antimetabolite antineoplastic agent, has been used to treat acute myeloid leukemia. However, due to its short half-life, maintaining an optimal plasma concentration necessitates continuous intravenous administration, which may result in toxicity to healthy cells and tissues. The purpose of the current investigation was to design and optimize biodegradable poly (lactic acid) (PLA) nanoparticles (NPs) for improved delivery of cytarabine against acute myeloid leukemia.</p><h3>Method</h3><p>The NPs were prepared using a double emulsion evaporation technique. A 3² factorial design was employed to optimize the particle size and entrapment efficiency. The developed NPs were analyzed for particle size, polydispersity, and zeta potential using the dynamic light scattering (DLS) technique. The morphological analysis of NPs was conducted using transmission electron microscopy (TEM). The compatibility of drugs and excipients was examined using attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy. The entrapment efficiency of NPs was determined using an indirect method. In vitro drug release was carried out by dialysis bag method. The toxicity of NPs to leukemic cells (KG-1) was determined by MTT assay. The in vivo pharmacokinetic study was performed on rabbits.</p><h3>Results</h3><p>A total of nine formulations (PL1-PL9) were developed, with particle sizes ranging from 135.8 ± 1.7 to 295.0 ± 3.2 nm and entrapment efficiencies ranging from 46.27 ± 5.30 to 70.33 ± 0.80%. The optimized formulation (PL9) exhibited a reduced particle size (179.3 ± 1.9 nm), improved entrapment efficiency (56.13 ± 6.50%), spherical morphology, negative zeta potential (−17 mV), better compatibility between the polymer and drug, and conversion of cytarabine from a crystalline to an amorphous form in the formulation. The in vitro release pattern of cytarabine from NPs exhibited a first quick release (18–40%), followed by a sustained release for up to 48 h. The sustained release further enhanced the toxicity of cytarabine-loaded PLA NPs to KG-1 cell lines. The in vivo pharmacokinetics study showed a better pharmacokinetic profile of PL9 than the control.</p><h3>Conclusion</h3><p>The study recommends that cytarabine-containing PLA NPs are a promising approach to overcome dose-limiting toxicity. The sustained release mechanism ensures maximum anti-leukemic effect and better pharmacokinetics.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"18 4","pages":"1713 - 1726"},"PeriodicalIF":2.6,"publicationDate":"2023-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42545211","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":"Lutein and β-Carotene Characterization in Free and Nanodispersion Forms in Terms of Antioxidant Activity and Cytotoxicity","authors":"Nourhan S. Elkholy,&nbsp;Mohamad Louai M. Hariri,&nbsp;Haitham S. Mohammed,&nbsp;Medhat W. Shafaa","doi":"10.1007/s12247-023-09745-2","DOIUrl":"10.1007/s12247-023-09745-2","url":null,"abstract":"<div><h3>Purpose</h3><p>Carotenoids are potent natural antioxidants with many important applications. Their nanodispersion formulations can solve problems that may limit their usage. In this study, we produced carotenoid nanodispersions from extracted lutein (nano-Lut), extracted β-carotene (nano-EBc), and synthetic β-carotene (nano-SBC).</p><h3>Methods</h3><p>The present study has quantitatively emphasized the physicochemical, antioxidant, and cytotoxic properties of free and nanodispersed formulations of lutein and β-carotene. The nanodispersions were characterized by spectral absorption, dynamic light scattering, and zeta potential. Antioxidant and cytotoxicity assays were conducted for free and their nanodispersed forms. The cytotoxicity of free carotenoids and their nanodispersions was conducted on HSF, VERO, and BNL cell lines.</p><h3>Results</h3><p>Nano-Lut has the smallest mean particle size (185.2 ± 40.5 nm, PDI of 0.183 ± 0.01, and zeta potential of −28.6 ± 6.4 mV). Nano-SBc showed monomodal size distribution (220.5 ± 30.09 nm, PDI of 0.318 ± 0.03, and zeta potential of −12.1 ± 5.9 mV), while nano-EBc showed a bimodal size distribution (with a mean particle size of 498.3 ± 88.9 nm, PDI of 0.65 ± 0.08, and zeta potential of −39.7 ± 1.3 mV). All prepared nanodispersions showed less than 20% loss during the formulation process. Antioxidant assays showed that extracted lutein was the most active and synthetic β-carotene was the least. Cells showed higher tolerance for lutein and its nanodispersion than extracted or synthetic β-carotene either in free or nanodispersion forms.</p><h3>Conclusions</h3><p>The study proved that lutein in nanodispersed form possesses the smallest size, the highest antioxidant activity, and the lowest cytotoxicity among the tested formulations.\u0000</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"18 4","pages":"1727 - 1744"},"PeriodicalIF":2.6,"publicationDate":"2023-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12247-023-09745-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48456901","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}