Journal of Pharmaceutical Innovation最新文献

{"title":"Preparation of pH-Sensitive Astragalus Polysaccharide Nanoparticles Loaded with Paclitaxel and Evaluation of Antitumor Activity","authors":"Kaibin Wang,&nbsp;Yanqiang Li,&nbsp;Xiaoliang Zhao,&nbsp;Tianke Zhu,&nbsp;Li Luo,&nbsp;Hanwen Zhang,&nbsp;Yonggang Wang,&nbsp;Jing Zhang,&nbsp;Cunjin Wang,&nbsp;Weijie Zhang","doi":"10.1007/s12247-024-09914-x","DOIUrl":"10.1007/s12247-024-09914-x","url":null,"abstract":"<div><h3>Purpose</h3><p>Chinese medicine polysaccharide are considered as promising medical materials due to their good biocompatibility and safety. The aim of this study was to develop a novel amphiphilic drug carrier based on astragalus polysaccharide (APS) to optimise the delivery of paclitaxel.</p><h3>Methods</h3><p>The pH-sensitive histidine (His) and hydrophobic stearic acid (SA) were grafted onto astragalus polysaccharide and self-assembled into nanoparticles by ultrasonication. The nanoparticles were characterised by Fourier transform infrared (FTIR), dynamic light scattering (DLS), zeta potential, transmission electron microscopy (TEM), and X-ray diffraction, and tested for encapsulation efficiency (EE%), drug loading capacity(LC%) and in vitro release of paclitaxel. The effects of nanoparticles on the proliferation of immune cells RAW264.7 and breast cancer cells SUM149 were assessed by cck-8 assay, and their effects on SUM149 cell cycle block and apoptotic protein expression were detected.</p><h3>Results</h3><p>The EE% of nanoparticles on paclitaxel was 77.61% and the LC% was 9.96%. Under acidic conditions, the surface charge of nanoparticles was reversed and the structure was swollen to promote drug release. Cellular experiments showed that blank nanoparticles could promote the proliferation of immune cells, and the anticancer effect of drug-loaded nanoparticles was significantly better than that of paclitaxel alone.</p><h3>Conclusion</h3><p>The prepared pH-sensitive nanoparticles can effectively enhance the uptake of paclitaxel by tumour cells and induce apoptosis in breast cancer cells, making them a promising new type of paclitaxel drug carrier.</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"20 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143109262","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":"3D Drug Printing by Semi-Solid Extrusion Through Reusable Cartridges: Usability Evaluation","authors":"Rohan Rege,&nbsp;Tessa Mellema,&nbsp;Arwin Ramcharan,&nbsp;Anouar Ait Hoummad,&nbsp;Sophie Verhoeven,&nbsp;Vibhas Mishra,&nbsp;Arjen J. Jansen,&nbsp;Niels Ouwerkerk,&nbsp;Fereshteh Shokri","doi":"10.1007/s12247-024-09904-z","DOIUrl":"10.1007/s12247-024-09904-z","url":null,"abstract":"<div><h3>Purpose</h3><p>Three-dimensional (3D) printing is revolutionising tablet fabrication in the field of pharmacy, offering personalised dosing through additive manufacturing techniques such as semi-solid extrusion (SSE). SSE traditionally uses disposable syringes, which pose challenges in temperature control and waste generation.</p><h3>Methods</h3><p>This article experimentally simulates various scenarios relevant to pharmacy practice to evaluate the usability of the semi-solid extrusion approach using a first-of-its-kind reusable cartridge. The research assesses the stability of formulations under thermal stress conditions that simulate commercial settings, demonstrating the robust performance of this 3D drug printing method across multiple uses.</p><h3>Results</h3><p>This study introduces pharmaceutical-grade stainless-steel cartridges as a sustainable alternative to disposable syringes, enhancing temperature management and reducing waste in SSE 3D printing.</p><h3>Conclusion</h3><p>Our findings highlight the potential of reusable cartridges to improve efficiency and sustainability in pharmaceutical manufacturing, with implications for future formulation developments and stability studies. The presented 3D drugprinting approach offers a promising solution for environmentally responsible practices in pharmacy.</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"20 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143109005","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":"Sodium Alginate Beads Containing Epalrestat for Effective Management of Diabetic Mellitus","authors":"Rashmi Madhariya,&nbsp;Alpana Ram,&nbsp;Akhlesh K. Jain","doi":"10.1007/s12247-024-09905-y","DOIUrl":"10.1007/s12247-024-09905-y","url":null,"abstract":"<div><h3>Purpose</h3><p>Epalrestat is the most common Aldose reductase inhibitor (ARI) approved for blood glucose management in several countries and has also shown efficacy in preventing the onset of diabetic neuropathy (DN), and diabetic retinopathy. The present study aims to formulate and evaluate the effectiveness of Alginate beads of epalrestat in Streptozotocin-induced (STZ) diabetic rats in order to effectively manage the diabetes.</p><h3>Method</h3><p>Various formulations of Sodium cross-linked alginate beads containing epalrestat (F1 to F9) were prepared based on full factorial design by ionotropic gelation method. The formulations were characterized for particle size, % Drug entrapment efficiency (DEE), Fourier Transform Infra-Red Spectroscopy (FT-IR), Differential scanning calorimetry (DSC), X-ray Diffraction Study (X-RD), Scanning Electron Microscopy (SEM), and In-Vitro Release Studies. Optimized formulation (F6) [containing sodium alginate (2.5%w/v), epalrestat (2.5%w/v), and calcium chloride (2.5%w/v)] was subjected to in-Vivo efficacy testing in diabetic rats.</p><h3>Result</h3><p>Epalrestat-loaded beads were prepared (F1 to F9; Size = 3.21 μm; DEE = 97%) successfully using sodium alginate as polymer and calcium chloride solution as the crosslinking agent by modified ionotropic gelation method Optimized formulation showed a % DEE of 97% and highest drug release of 95% at the end of 10 hrs. Drug Release Kinetic of optimized formulation followed first-order kinetic. Further, the hypoglycemic effect was observed over a longer period 50% reduction after 2 hrs and continued till 4 hrs. In addition, normoglycemia was maintained till 12 hrs (20% reduction) in STZ-induced diabetic rats.</p><h3>Conclusion</h3><p>The formulation F6 was found to be superior compared to all the other formulations because the percentage drug entrapment efficiency was highest and there was no chemical interaction took place between the drug and polymer (Confirmed by DSC and XRD studies). In-vivo study showed prolonged hypoglycaemia till 12 hrs with a maximum reduction at 2 hrs Compared to plain drug suspension (20% reduction till 5 hrs).</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":"20 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142995621","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":"Unveiling the Therapeutic Potential: Okra-Derived Flavonoids in Breast Cancer Treatment","authors":"Anum Munir,&nbsp;Alan Janbey","doi":"10.1007/s12247-024-09920-z","DOIUrl":"10.1007/s12247-024-09920-z","url":null,"abstract":"<div><h3>Introduction</h3><p>The increased incidence and high global death rates of breast cancer make it a major global health problem. New therapeutic techniques are still needed, especially those that focus on certain molecular pathways that have been linked to the development and progression of breast cancer, even with the advancements in treatment strategy. Due to their wide range of biological activity and generally low safety profiles, chemicals originating from plants especially flavonoids, have shown promise as possible anti-cancer medicines.</p><h3>Methods</h3><p>We sought to determine if flavonoids from <i>Abelmoschus esculentus</i> (okra) seeds might prove useful in the treatment of breast cancer. Six major subgroups of flavonoids found in okra seeds were discovered after a thorough examination of the literature, and their potential anti-cancer benefits were investigated.</p><h3>Results</h3><p>Oestrogen receptor alpha (ESR1), protein kinase B (AKT1), and the epidermal growth factor receptor (EGFR) were among the proteins linked to breast cancer whose binding modes and affinities were predicted using molecular docking simulations. Moreover, genes that are differently expressed in breast cancer cell lines were found using high throughput gene sequencing data analysis.</p><h3>Discussions</h3><p>Based on our research, certain flavonoids from okra seeds could interact with important proteins that are involved in the initiation and spread of breast cancer, providing information on potential treatment strategies. However, more experimental validation is required to validate these results and clarify the therapeutic significance of flavonoids produced from okra in treating breast cancer.</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"20 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142994917","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":"Computational Identification of Bioactive Molecules from Caralluma stalagmifera L. as Potential VEGFR2 Inhibitors for Endometriosis Treatment","authors":"Joseph Sahayarayan Jesudass,&nbsp;Balasubramanian Sivaprakasam,&nbsp;Soundar Rajan Kulanthaivel,&nbsp;Arun Muthukrishnan,&nbsp;Rajasekar Chinnaiyan,&nbsp;Rajendran Ramasamy,&nbsp;Saud Alarifi,&nbsp;Anis Ahamed,&nbsp;Ravishankar Ram Mani,&nbsp;Soon Woong Chang,&nbsp;Ravindran Balasubramani","doi":"10.1007/s12247-024-09894-y","DOIUrl":"10.1007/s12247-024-09894-y","url":null,"abstract":"<div><h3>Objectives</h3><p>Endometriosis is a gynecological condition characterized by the growth of uterine tissue outside the uterus, primarily affecting the peritoneal cavity and disrupting the female reproductive system due to estrogen. This study investigates the potential of phytochemicals from <i>Caralluma stalagmifera L.</i> to inhibit Vascular Endothelial Growth Factor Receptor-2 (VEGFR2), which plays a crucial role in blood vessel formation and inflammation associated with endometriosis.</p><h3>Methods</h3><p>Gas Chromatography-Mass Spectrometry (GC-MS) analysis was utilized to identify active compounds in <i>Caralluma stalagmifera L.</i>, particularly those with anti-inflammatory properties. Key compounds included ethyl 2-[(4R,6R)-2,2-dimethyl-6-pentyl-1,3-dioxan-4-yl]acetate and Thioacetic acid S-(tetrahydro-2 H-pyran-3-yl) ester. Molecular docking and Molecular Dynamics (MD) simulations were conducted to examine their interactions with VEGFR2.</p><h3>Results</h3><p>Among the compounds tested, ethyl 2-[(4R,6R)-2,2-dimethyl-6-pentyl-1,3-dioxan-4-yl]acetate displayed the most favorable docking score with VEGFR2. The stability of this interaction was further supported by Root Mean Square Deviation (RMSD) and Root Mean Square Fluctuation (RMSF) analyses, which demonstrated minimal fluctuations during simulations. Additionally, hydrogen bond formations between the compound and VEGFR2 were observed, suggesting a stable binding environment. The binding free energy calculations reinforced the potential of this compound as a viable inhibitor. Furthermore, Density Functional Theory (DFT) analysis provided insights into the electrostatic properties of the ligand-protein complex, highlighting its stability and interaction dynamics compared to synthetic drugs.</p><h3>Conclusions</h3><p>Phytochemicals from <i>Caralluma stalagmifera L.</i>, especially ethyl 2-[(4R,6R)-2,2-dimethyl-6-pentyl-1,3-dioxan-4-yl]acetate, show promise in inhibiting VEGFR2, suggesting their potential as therapeutic agents for managing inflammation in endometriosis. Further studies are needed to validate these findings and assess their clinical applications.</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"20 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142994955","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":"Moisture Content Prediction Model for Pharmaceutical Granules Using Machine Learning Techniques","authors":"Haftom Kahsay Tekie,&nbsp;Tibebe Beshah,&nbsp;Fisha Haileslassie,&nbsp;Samuel Tesfay","doi":"10.1007/s12247-024-09918-7","DOIUrl":"10.1007/s12247-024-09918-7","url":null,"abstract":"<div><h3>Purpose</h3><p>ML techniques are powerful and novel approaches in modeling fluid bed drying of pharmaceutical granules. The aim of this study was to develop a prediction model and identify relative important factors in the evaluation of moisture content of pharmaceutical granules using ANN and SVM techniques for the datasets of APF. </p><h3>Methods</h3><p>ANN and SVM models were developed and compared, utilizing matlab 16.0a as a software tool. Optimizations of the models were also conducted applying GDR and improved TLCO techniques for FFNN and epsilon-SVR, respectively. The performance of the models was evaluated using a quantitative error metric: MAE, MSE, and R².</p><h3>Results</h3><p>This study reveals that the FFNN model is an optimal model for predicting moisture content of pharmaceutical granules for the TSG-FBD process model for the datasets of APF.</p><h3>Conclusions</h3><p>The model of FFNN, with MSE of 0.0009 and R² of 0.987, is built and accepted as an optimal model for predicting the moisture content of pharmaceutical granules. <i>Temperature, inlet airflow-rate, initial moisture, drying time, and screw speed</i>, respectively are the most important factors in determining the moisture content of the granules.</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"20 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142994769","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 and Characterization of Novel Solid Self Nanoemulsifying Drug Delivery System of Fimasartan","authors":"Rajnikant Suthar,&nbsp;Ajay Solanki,&nbsp;Rajesh Palva,&nbsp;Prajesh Prajapati,&nbsp;Umang Shah,&nbsp;Krunal Detholia","doi":"10.1007/s12247-024-09921-y","DOIUrl":"10.1007/s12247-024-09921-y","url":null,"abstract":"<div><h3>Purpose</h3><p>The objective of the present study was to prepare a solid self-nano emulsifying drug delivery system (S-SNEDDS) of Fimasartan Potassium Trihydrate (FPT), a poorly water-soluble antihypertensive agent.</p><h3>Methods</h3><p>Equilibrium Solubility study and ternary phase diagram study were conducted for screening of excipients. D-optimal Mixture design was employed to optimise the formulation variables, X₁ (amount of oil; Capmul MCM C8), X₂ (amount of surfactant; Labrasol) and X₃ (amount of co-solvent; Transcutol HP). Self-emulsification time (Y₁), percentage transmittance (Y₂) and mean globule size (Y₃) were set as response variables. Optimised liquid SNEDSS (L-SNEDDS) formulation was further assessed for robustness to dilution, thermodynamic stability study, cell viability and TEM analysis. L-SNEDDS was converted into free flowing powder (S-SNEDDS) by adsorption on the porous carrier like Neusilin US2 and thereafter filled in hard gelatin capsules (HGC). Prepared HGC was further evaluated for in-vitro dissolution, stability and bioavailability study.</p><h3>Results</h3><p>The optimized L-SNEDDS formulation consists of 20% oil, 40% surfactant, and 40% co-solvent, demonstrating strong thermodynamic stability and safety for cellular use.TEM analysis demonstrated that the nanoemulsion comprised spherical, uniformly sized globules. When testing the in vitro dissolution of HGC derived from FPT-loaded S-SNEDDS, there was a noticeable increase in the drug's dissolution rate, achieving 98% drug release within 30 min. Additionally, subsequent stability testing in accordance with ICH guidelines over a six-month period indicated that the HGC remained stable, with no significant alterations in its physicochemical characteristics. The bioavailability study indicated a significant enhancement, with a 1.5-fold increase in the relative bioavailability of S-SNEDDS in comparison to the pure drug.</p><h3>Conclusion</h3><p>Based on the results obtained, it has been concluded that S-SNEDDS, with its ability to create a nanometric dispersion of controllable size, enhances the solubility, dissolution, bioavailability and stability of the encapsulated FPT drug more effectively than conventional dosage forms.</p><p>Present study demonstrated an increase in dissolution and improved bioavailability for FPT. In conclusion, the results of this study indicate the potential use of the developed S-SNEDDS formulation for delivering the active ingredient.</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"20 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142994768","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":"Formulation and Development of Posaconazole Loaded Controlled Release Nanosponge Topical Gel for the Treatment of Fungal Infection","authors":"Rupal K. Jani,&nbsp;Zeel M. Patel,&nbsp;Kaushal J. Jani,&nbsp;Nidhi N. Patel,&nbsp;G. S. Chakraborthy,&nbsp;Vijay J. Upadhyay,&nbsp;Mukesh Chandra Sharma,&nbsp;Shailesh Wadher,&nbsp;Sunil Tulshiram Hajare","doi":"10.1007/s12247-024-09912-z","DOIUrl":"10.1007/s12247-024-09912-z","url":null,"abstract":"<div><h3>Purpose</h3><p>The main purpose of this study is to synthesize posaconazole as a nanosponge device to evaluate its antifungal potential, specifically for the treatment of cutaneous candidiasis caused by the <i>Candida albicans</i> fungus.</p><h3>Methods</h3><p>Posaconazole inhibits fungi by acting on their cell membrane through its antifungal action. Posaconazole nanosponges made using a solvent preparation technique. The polymer methyl-β-cyclodextrin was utilized to make the nanosponge. Particle size, entrapment effectiveness, drug content, and scanning electron microscopy were assessed for nanosponge formulations. Carbopol 934, preservatives, and a few more pH adjacent ingredients are used in the gel production process. Evaluation tests for spreadability, viscosity, gelling strength, pH, and in vitro diffusion of gels loaded with nanosponges.</p><h3>Results</h3><p>The F4 formulation’s entrapment efficiency was determined to be 562.7 ± 0.036 nm with 99.24 ± 0.016% of Entrapment efficiency. Viscosity 47879 ± 0.546 cps, Spreadability 13.09 ± 0.065 g.cm/s, pH 6.54 ± 0.004, and gelling strength 112 sec.% are all displayed in the optimized batch of nanosponge loaded gel. The improved batch’s drug diffusion was determined to be 95.58 ± 0.079% for a full day. Studies on skin irritation and stability testing of the improved formulation were performed. The formulation may offer prolonged release and enhanced drug bioavailability, boosting the medication's therapeutic efficacy, according to the high entrapment efficiency and suitable particle size.</p><h3>Conclusion</h3><p>The formulation’s excellent entrapment efficiency and adequate particle size imply prolonged drug release and increased bioavailability, improving therapeutic effectiveness. As a result, the study provides a strong basis for the creation of topical antifungal medications that work.</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"20 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142994471","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":"Deciphering the Impact of Hyaluronic Acid Grafting Density and Molecular Weight on Paclitaxel Liposome in CD-44 Receptor Targeting","authors":"Mahendra Kumar Prajapati,&nbsp;Aniketh Bishnu,&nbsp;Satish Rojekar,&nbsp;Rohan Pai,&nbsp;Pritha Ray,&nbsp;Pradeep R. Vavia","doi":"10.1007/s12247-024-09899-7","DOIUrl":"10.1007/s12247-024-09899-7","url":null,"abstract":"<div><h3>Purpose</h3><p>The biggest challenge in developing efficacious anticancer formulations is to improve their targeting specificity and reducing toxicity. For this purpose, HA anchored paclitaxel liposomes (HA-PTX-LIP) were fabricated using synthesized conjugate HA-DSPE (HA Molecular Weight- 12, 76, and 160–200 kDa).</p><h3>Methods</h3><p>Maximum in vitro cell targeting was observed with 160–200 kDa HA-PTX-LIP compared to 11 and 76 kDa HA-PTX-LIP, indicating HA’s MW-dependent HA-CD44 binding and internalization. Further, the effect of grafting density (HA/L ratio- μg HA-DSPE/μmol Lipid) of 160–200 kDa HA-DSPE on tumor targeting was evaluated in vitro at three different levels (low-20 μg/μmol, mid-50 μg/μmol, and high- 100 μg/μmol).</p><h3>Results</h3><p>HA/L -100 exerted the highest in vitro tumor-targeting potential. Upon in vivo evaluation, 160–200 kDa HA-PTX-LIP (HA/L-100) exhibited 18.11 and 27.4-fold improved AUC and MRT, respectively, compared to the marketed formulation. Moreover, it showed improved biodistribution with less organ AUC (liver, spleen, and kidney) when compared with the marketed formulation. A significant reduction in ROS generation suggested decreased tumor incidence. Compared to the control and marketed formulations, the modified liposome showed increased targeting potential in the in vivo antitumor efficacy on the ovarian tumor model, resulting in a 4.88 and 2.81-fold reduction in tumor volume. Compared to the control and commercial formulations, tumor weight was also reduced by 1.48 and 1.11-fold. Animal survival was 100 percent with 160–200 kDa HA-PTX-LIP (HA/L-100) without significant weight loss.</p><h3>Conclusion</h3><p>The findings suggest the possibility of rationalizing HA's molecular weight and grafting density for efficient in vivo ovarian tumor targeting.</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":"20 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142994472","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":"The Assessment of Vaginal permeability – in silico Approach","authors":"Sonja Pop-Trajkovic Dinić,&nbsp;Milan Trenkić,&nbsp;Aleksandar Živadinović,&nbsp;Predrag Vukomanović,&nbsp;Milan Stefanović,&nbsp;Dejan Mitić,&nbsp;Jelena Stevanović Milošević,&nbsp;Aleksandar M. Veselinović","doi":"10.1007/s12247-024-09887-x","DOIUrl":"10.1007/s12247-024-09887-x","url":null,"abstract":"<div><h3>Purpose</h3><p>Intravaginal drug administration offers a notable alternative to traditional oral delivery methods, allowing for precise targeting of effects both locally and systemically. In response to this, there has been a notable increase in the development of advanced <i>in silico</i> techniques for predicting drug permeability. These methods prove to be advantageous by bypassing the lengthy and resource-intensive processes typically associated with in vitro and in vivo experiments. </p><h3>Methods</h3><p>This particular study delved into the creation of<i> in silico</i> models specifically tailored for predicting vaginal permeability. The models were meticulously constructed using SMILES descriptors and local molecular graph invariants, ensuring a conformation-independent QSAR model. Leveraging a Monte Carlo optimization strategy, the models were iteratively refined across three distinct molecular splits for training and testing purposes.</p><h3>Results</h3><p>For the best developed QSAR model following statistical parameters were obtained for training set r² = 0.7152, CCC = 0.8340, IIC = 0.7572, q² = 0.7011, RMSE = 0.0055, MAE = 0.0044 and F = 196; and for test set r² = 0.8657, CCC = 0.8902, IIC = 0.6180, q² = 0.8412, R_m² = 0.6722, RMSE = 0.0040, MAE = 0.0030 and F = 168.</p><h3>Conclusions</h3><p>These results underscored the exceptional predictive capabilities and robustness of the QSAR models developed in this study. Furthermore, the analysis pinpointed key molecular fragments derived from SMILES descriptors that significantly influence placental permeability. Given the prevalence of SMILES notation in most molecular databases, these well-constructed QSAR models can effectively serve as a rapid and precise screening tool for evaluating vaginal permeability.</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":"20 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12247-024-09887-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142976591","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}