Pharmaceutics最新文献

{"title":"Brazilian Red Propolis Extract-Loaded Colloidal Systems Derived from Microemulsion Compositions: Physicochemical, Antioxidant, and Antileishmanial Properties.","authors":"Salvana P M Costa, Ighor C Barreto, Kathylen V F Dos Santos, Nataly C S Gama, Monique A Vila Nova, Victor Hugo V Sarmento, Louisianny G da Rocha, Irinaldo D Basílio, Camila M B R G Panjwanig, Ticiano G do Nascimento","doi":"10.3390/pharmaceutics18101284","DOIUrl":"https://doi.org/10.3390/pharmaceutics18101284","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Brazilian red propolis is a rich source of isoflavonoids with promising antioxidant and antileishmanial activities. However, its poor aqueous solubility and chemical instability limit its pharmaceutical application. This study aimed to develop microemulsion-based systems containing high concentrations of Brazilian red propolis extract (RPE) and evaluate their physicochemical properties, phytochemical composition, antioxidant capacity, and antileishmanial activity. <b>Methods</b>: Pseudoternary phase diagrams were constructed by water titration to select suitable microemulsion compositions. RPE was subsequently incorporated into the selected compositions to obtain RPE-loaded colloidal systems. The three selected RPE-free microemulsions and their corresponding RPE-loaded systems were characterized by pH, electrical conductivity, dynamic light scattering, rheological measurements, and polarized light microscopy (PLM). The RPE-loaded systems were further evaluated for phenolic marker content, antioxidant activity, and in vitro activity against <i>Leishmania</i> infantum. <b>Results</b>: Three RPE-loaded colloidal systems (F2-RPE12, F3-RPE30, and F4-RPE50) were developed. F2-RPE12 exhibited characteristics consistent with an oil-in-water microemulsion. Conductivity and PLM indicated physicochemical changes after RPE incorporation in F3-RPE30 and F4-RPE50, with localized birefringent features at higher RPE concentrations. Among the RPE-loaded systems, F4-RPE50 showed the highest phenolic and flavonoid contents and antioxidant activity. The RPE-loaded systems exhibited lower IC₅₀ values than RPE alone, with IC₅₀ values of 3.14, 2.28, and 0.56 µg·mL^-1 for F2-RPE12, F3-RPE30, and F4-RPE50, respectively, compared with 5.90 µg·mL^-1 for RPE. <b>Conclusions</b>: Overall, F4-RPE50 showed the most favorable phytochemical and biological performance, and the physicochemical and optical changes observed in the RPE-loaded systems open new avenues for investigating the relationship between structural organization and formulation performance.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 10","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149271788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preparation and Investigation of Solvatomorphs of Anti-Tumor Candidate RA-XII.","authors":"Feng Cao, Song Zhang, Qicheng Duan, Haitao Dou, Yinghui Liang, Ninghua Tan","doi":"10.3390/pharmaceutics18101285","DOIUrl":"https://doi.org/10.3390/pharmaceutics18101285","url":null,"abstract":"<p><p>RA-XII, a unique natural cyclopeptide, is a potential anti-colorectal cancer candidate by mainly inhibiting protective autophagy, SREBP-1-dependent lipid biogenesis and suppressing activation of the Akt-mTOR pathway in HCT-116 cells. However, there have been no investigations into its solid forms, and its poor solubility restricts its application in the development of clinical anticancer agents. <b>Background/Objectives</b>: To investigate and develop advantageous medicinal solid forms of RA-XII and further improve its solubility characteristics. <b>Methods</b>: Various recrystallization methods were used to screen crystal forms of RA-XII, and single crystals (Forms I, II and V) were obtained by the vapor diffusion method. The forms were characterized by powder X-ray diffraction (PXRD), spectroscopy (FTIR, Raman), thermal analyses (DSC, TGA) and scanning electron microscopy (SEM). Structural parameters were determined by single crystal X-ray diffraction (SCXRD). The solubility and intrinsic dissolution rate were determined in a pH 7.4 pharmaceutical buffer solution with water. Hirshfeld surface analyses, molecular electrostatic potential surface (MEPs) analyses and molecular dynamics (MD) simulations were employed to reveal differences in hydrogen bond interactions of the crystal structure. <b>Results</b>: Five solvatomorphs and an amorphous form of RA-XII were successfully obtained. Then, three single crystals of Forms I, II and V were obtained, and their conformations were investigated. Hirshfeld surface analyses and crystal structures revealed significant differences in hydrogen bonding interactions and molecular packing. Moreover, MEPs analyses and MD suggested the formation mechanisms of RA-XII solvatomorphs, in which the hydrogen bonding strengths increase between RA-XII and solvent molecules. <b>Conclusions</b>: Form I is physically more stable and exhibits great solubility in water. Form I possesses significant medicinal advantages. These findings provide valuable insights into understanding the solvatomorph mechanisms and the quality control of RA-XII.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 10","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149271771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preparation of Excipient-Free Molnupiravir Microparticles for Pulmonary Drug Delivery and Process Evaluation via Machine Learning.","authors":"Juncheng Hu, Yucheng Huang, Jiahao Luo, Jiayi Wang, Haoyang Chen, Minghao Lian, Ning Xue, Xiang Luo, Kaiqi Shi, Bin Dong, Hanhan Li","doi":"10.3390/pharmaceutics18101290","DOIUrl":"https://doi.org/10.3390/pharmaceutics18101290","url":null,"abstract":"<p><p><b>Background/Objective:</b> Molnupiravir (EIDD-2801) was originally designed to treat influenza A virus and showed broad-spectrum antiviral activity, including against influenza virus, Ebola virus, coronavirus and other viruses. <b>Methods:</b> In this study, molnupiravir microparticles were firstly prepared by spray freeze-drying (SFD) and jet milling (JM) methods. Meanwhile, machine learning methodology was applied to evaluate the influence of process parameters such as feeding rate, concentration, and nebulization pressure on powder properties. <b>Results:</b> According to SEM images, the microparticles prepared by SFD presented a porous and near-spherical structure. Moreover, the fine particle fraction (FPF) and mass median aerodynamic diameter (MMAD) of the optimal inhalable powder reached up to 70.19 ± 2.06% and 2.80 ± 0.16 μm, proving the excellent aerodynamic performance. <b>Conclusions:</b> The molnupiravir micropowder showed preliminary short-term storage behavior after storage for 28 days at 25 °C and 60% RH.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 10","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149271890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D-Printed Gastroretentive Floating Modified-Release Device for Dual Cardiovascular Drug Delivery: Isosorbide Dinitrate and Hydralazine.","authors":"Dareena Jaiseri, Supusson Pengnam, Praneet Opanasopit, Phuvamin Suriyaamporn, Chaiyakarn Pornpitchanarong, Theerasak Rojanarata, Boonnada Pamornpathomkul, Prasopchai Patrojanasophon, Teeratas Kansom, Thapakorn Charoenying","doi":"10.3390/pharmaceutics18101278","DOIUrl":"https://doi.org/10.3390/pharmaceutics18101278","url":null,"abstract":"<p><p><b>Background</b>: Isosorbide dinitrate (ISDN) and hydralazine hydrochloride (HDZ) are dual cardiovascular drugs used to treat heart failure. However, the drugs have limitations such as short plasma half-life, low bioavailability, and potential for tolerance of the nitrate component. To address the need for prolonged drug release, a floating dual-compartment drug delivery system was developed to provide controlled drug release under simulated gastric dissolution conditions. <b>Objectives</b>: This study aimed to develop floating dual-compartment devices (FDCDs) to contain ISDN and HDZ gel and modify drug release under simulated gastric conditions. <b>Methods</b>: The FDCD was designed in a cylindrical shape consisting of an air chamber on the upper part for floating ability, and two compartments for loaded drug gel and controlling the drug release rate. Fused deposition modeling (FDM) was selected to fabricate FDCDs using polylactic acid (PLA) filament. The ISDN formulation varied the ratio of polyvinylpyrrolidone (PVP) to achieve drug release for 12 h. The HDZ formulation was optimized by varying the ratio of PVP and hydroxypropyl methylcellulose (HPMC) to extend drug release at 24 h. <b>Results</b>: The shape dimension and weight variation in the FDCDs showed low standard deviation (SD). FDCDs exhibited immediate floating, resisted overturning, and demonstrated in vitro floating ability for more than 24 h. The formulation ISDN3 at a PVP: drug: water ratio of 5:2:3 exhibited complete release at 12 h, while the formulation of HDZ1 at an HPMC: PVP: drug: water ratio of 0.3:2.5:2:5.2 showed complete release within 24 h. The ISDN3- and HDZ1-loaded FDCDs demonstrated prolonged release behavior, with ISDN and HDZ release profiles showing the best fit to the zero-order and Higuchi models, respectively, based primarily on the coefficient of determination (R²), while root mean square error (RMSE) was used as a complementary measure of fitting error. <b>Conclusions</b>: These findings suggest that the developed dual-drug-loaded FDCD has potential as a dual-drug oral delivery platform for simultaneous delivery of ISDN and HDZ with prolonged drug release characteristics and further development of oral combination drug delivery systems.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 10","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149271748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myricetin Modulates Quorum Sensing-Associated Phenotypes, Virulence, and Biofilm Formation in Pathogenic Bacteria: In Vitro and In Silico Studies.","authors":"Abdulrahman S Bazaid, Nizar H Saeedi, Mohammed M Jalal, Almohanad A Alkayyal, Mitesh Patel, Abdu Aldarhami","doi":"10.3390/pharmaceutics18101280","DOIUrl":"https://doi.org/10.3390/pharmaceutics18101280","url":null,"abstract":"<p><p><b>Background/Objectives:</b> The rapid emergence of antimicrobial resistance (AMR) among pathogenic bacteria has necessitated the development of alternative therapeutic strategies that target bacterial virulence rather than cell viability. <b>Methods:</b> In this study, the flavonoid myricetin was systematically evaluated for its antibacterial, QS-associated phenotypic and biofilm formation-inhibitory activities against clinically relevant bacterial pathogens. <b>Results:</b> Myricetin exhibited moderate antibacterial activity and significantly reduced several QS-associated phenotypes. Violacein and prodigiosin production were reduced by 74.59% and 64.32%, respectively, consistent with QS-modulatory activity under the tested conditions. Furthermore, myricetin markedly attenuated key virulence factors in <i>Pseudomonas aeruginosa</i>, including pyocyanin (70.44%), pyoverdine (75.84%), and rhamnolipids (48.69%). In addition, concentration-dependent reductions in biofilm formation and extracellular polymeric substance (EPS) production was observed across all tested strains. Molecular docking predicted favourable interactions of myricetin with key QS regulatory proteins, particularly CviR and LasR, which was supported by molecular dynamics simulations. Notably, the LasR-myricetin complex showed greater computational stability among the evaluated complexes, supporting its potential role as a key interaction site. <b>Conclusions:</b> This study provides an integrated experimental and computational evaluation of myricetin-mediated modulation of QS-associated phenotypes across multiple bacterial systems, demonstrating reductions in virulence-factor production and biofilm formation under the tested conditions. Collectively, these findings position myricetin as a promising anti-virulence candidate, although further studies are required to validate its clinical applicability.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 10","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149271960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retatrutide as a Unimolecular GIP/GLP-1/Glucagon Receptor Tri-Agonist: Molecular Design, Pharmaceutical Development and Critical Interpretation of Emerging Phase 3 Evidence.","authors":"Diana-Maria Mateescu, Ionut Dragos Capraru, Bogdan Enache, Alexandra Enache, Cris Virgiliu Precup, Camelia Liana Buhaș, Camelia-Oana Muresan","doi":"10.3390/pharmaceutics18101277","DOIUrl":"https://doi.org/10.3390/pharmaceutics18101277","url":null,"abstract":"<p><p>Retatrutide (LY3437943) is an investigational, once-weekly, lipidated 39-residue peptide that activates the glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1, and glucagon receptors. Its molecular design combines incretin activity with glucagon receptor engagement while maintaining glycaemic efficacy. This critical narrative review examines molecular engineering, pharmacokinetics, dose escalation, pharmaceutical development, and clinical evidence available through 11 September 2026. Five phase 3 trials have reported positive primary outcomes, but only TRANSCEND-T2D-1 has a full peer-reviewed report; the obesity trials are currently available as sponsor topline disclosures. In those disclosures, efficacy-estimand mean weight reductions of 28.3% at 80 weeks (TRIUMPH-1) and 28.7% at 68 weeks (TRIUMPH-4) were reported, with a TRIUMPH-1 treatment-regimen estimate of 25.0%; these values remain provisional pending full published trial reports. The peer-reviewed TRANSCEND-T2D-1 report supports glycaemic efficacy in early type 2 diabetes. Interpretation requires attention to estimands, population differences, treatment discontinuation and selection into trial extensions. Gastrointestinal adverse events, dysaesthesia, heart-rate changes and the functional consequences of lean-mass loss require further evaluation. Pharmaceutical priorities include scalable synthesis, impurity and potency control, formulation stability, immunogenicity and reliable dose delivery. Retatrutide provides a clinically advanced example of unimolecular poly-agonism, but comparative effectiveness, long-term outcomes and regulatory review remain essential to defining its therapeutic role.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 10","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149271896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mannose-Functionalized Polymeric Micelles Target CD206-Expressing Macrophages Within Human Tuberculosis Granulomas and Improve Isoniazid Delivery.","authors":"Camila Belen Martinena, Facundo Guillermo Ortellado, Agustín Daniel Vitti, Candela Martin, Ana Julia Bazán Bouyrie, Ezequiel Bernabeu, Rocío Zuazo, Diego Andrés Chiappetta, Verónica Edith García, Nicolas Oscar Amiano, Marcela Analia Moretton, Nancy Liliana Tateosian","doi":"10.3390/pharmaceutics18101279","DOIUrl":"https://doi.org/10.3390/pharmaceutics18101279","url":null,"abstract":"<p><p><b>Background</b>: Latent tuberculosis infection (LTBI) remains a global health challenge, in part due to the ability of <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) to persist within granulomatous lesions where drug exposure may be limited. Because granulomas are heterogeneous structures composed of different macrophage populations, targeting disease-relevant intracellular niches may improve antimicrobial treatment. Here, we developed mannose-functionalized polymeric micelles loaded with isoniazid (INH) to target mannose receptor (CD206)-expressing macrophages within a human tuberculosis granuloma model. <b>Methods</b>: Mannose-functionalized Soluplus^® micelles loaded with INH (ManPM-INH) and non-functionalized micelles (PM-INH) were characterized for particle size, polydispersity, and colloidal stability. Antimycobacterial activity against <i>Mtb</i>H37Rv was evaluated by CFU assays. A human peripheral blood mononuclear cell (PBMC) three-dimensional in vitro granuloma model was used to assess micelle accumulation and antimycobacterial activity. Cellular uptake was evaluated in M0, M1, and M2 macrophages using rhodamine-labeled micelles. CD206-associated and clathrin-mediated uptake were investigated using D-mannose and chlorpromazine, respectively. <b>Results</b>: ManPM-INH exhibited suitable physicochemical properties and maintained colloidal stability after mannose functionalization. In the granuloma model, ManPM showed significantly greater intracellular accumulation than PM. M2-like macrophages predominated within granulomas, and ManPM displayed preferential uptake by M2 macrophages. Furthermore, D-mannose competitively reduced ManPM uptake in macrophages with significantly greater inhibition in M2 cells. Chlorpromazine reduced ManPM internalization, supporting involvement of a clathrin-dependent pathway. ManPM-INH achieved the greatest reduction in intracellular <i>Mtb</i>H37Rv burden compared with INH and PM-INH, particularly at low drug concentrations. <b>Conclusions</b>: Mannose-functionalized micelles enhance intracellular INH delivery by targeting CD206-expressing macrophages within tuberculosis granuloma, supporting macrophage-targeted nanotherapeutic strategies against persistent intracellular <i>Mtb</i>.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 10","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149271912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbiota-Gut-Brain Axis Interactions with CNS Drugs: A Critical Mechanistic Review of Biopharmaceutical, Pharmacokinetic, and Pharmacodynamic Evidence.","authors":"David Stepensky","doi":"10.3390/pharmaceutics18101276","DOIUrl":"https://doi.org/10.3390/pharmaceutics18101276","url":null,"abstract":"<p><p><b>Background/Objectives</b>: The microbiota-gut-brain axis (MGBA) modifies central nervous system (CNS) pharmacotherapy by influencing the biopharmaceutics, pharmacokinetics (PK), and pharmacodynamics (PD) of drugs, while CNS drugs reciprocally reshape the MGBA. This review examines these interactions and their clinical relevance, explicitly grading the strength of the evidence. <b>Methods</b>: This narrative, mechanistically oriented review focuses on four oral drugs representing distinct mechanistic archetypes: levodopa/carbidopa (biopharmaceutical-dominant), olanzapine (PK-dominant), sertraline (PD-dominant), and amitriptyline (mixed). PubMed/MEDLINE, Google Scholar, and Google were searched up to 1 September 2026; of approximately 260 records screened, 64 were cited. No PRISMA reporting or dual screening was performed. Findings were assigned to five evidence tiers (L1-L5) and classified as associative or causal. <b>Results</b>: For levodopa/carbidopa, fecal tyrosine decarboxylase (<i>tdc</i>) gene abundance correlates with daily dose requirement (human observational), and <i>Helicobacter pylori</i> eradication or treatment of small intestinal bacterial overgrowth improves levodopa exposure or motor outcomes (human interventional). For olanzapine, microbiota depletion increased bioavailability ~1.8-fold in rats (single study), and microbiome-dependent weight gain is causal in rodents, whereas human data are phenomenological only. For sertraline, antimicrobial activity and fecal depletion are demonstrated in vitro; the pharmacodynamic blockade derives from fluoxetine models. For amitriptyline, antimicrobial and anticholinergic effects are preclinical, and the ATLANTIS trial demonstrates efficacy in irritable bowel syndrome without measuring the microbiome. <b>Conclusions</b>: The microbiome is a measurable modifier of CNS drug fate, but few interactions are clinically actionable. Progress requires prospective trials with standardized MGBA biomarkers, microbiome-informed PK/PD models, and independent replication.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 10","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149271950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progress in Anti-Obesity Drug Development: A Pharmacodynamics Perspective.","authors":"Ishtiaque Ahmad, Sarfuddin Azmi, Monirah A Albabtain, Mohammad Mustafa, Faisal Kunnathodi, Riyasdeen Anvarbatcha, Bander R AlWhaiby, Emtenan M Alharbi, Amr A Arafat, Haifa F Alotaibi","doi":"10.3390/pharmaceutics18101281","DOIUrl":"https://doi.org/10.3390/pharmaceutics18101281","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Obesity is a chronic, multifactorial condition driven by complex neuroendocrine and metabolic pathways that limit the long-term success of lifestyle interventions. Pharmacotherapy has advanced from early monoaminergic agents to incretin-based and multi-receptor agonists with substantially improved efficacy. This review aims to provide pharmacodynamics-focused synthesis of current and emerging anti-obesity medications, emphasizing mechanistic targets, receptor interactions, and translational implications. <b>Methods:</b> We conducted a narrative review integrating Phase I-III clinical trials, mechanistic pharmacology data (receptor affinity, potency, and signaling bias), and regulatory summaries for FDA-approved and selected emerging, investigational, repurposed, or regionally approved anti-obesity agents. Inclusion focused on clinical relevance, pharmacodynamic novelty, and weight-loss efficacy. <b>Results:</b> Approved anti-obesity medications act through diverse pathways, including the inhibition of fat absorption (orlistat), the modulation of central appetite circuits (phentermine/topiramate, naltrexone/bupropion), and incretin-based mechanisms (liraglutide, semaglutide, tirzepatide, and the oral GLP-1 receptor agonists semaglutide 25 mg and the nonpeptide orforglipron). GLP-1 receptor agonists achieve approximately 6-15% weight loss, while dual glucose-dependent insulinotropic polypeptide/GLP-1 receptor agonists such as tirzepatide reach 15-20%. Emerging agents-including triple agonists (retatrutide), glucagon-based co-agonists, amylin analogs with Phase III efficacy data, earlier-stage growth differentiation factor 15 (GDF15) pathway agonists, and peripherally restricted cannabinoid-1 receptor inverse agonists-demonstrate enhanced metabolic effects and potential improvements in lean-mass preservation. Obesity-related alterations in pharmacokinetics and pharmacodynamics highlight the need for individualized dosing strategies. <b>Conclusions:</b> Clinical efficacy and tolerability cannot be inferred from receptor identity alone. They emerge from relative receptor potency and efficacy, exposure, tissue access, receptor trafficking, and mechanism-linked adverse effects. Dual and triple agonists can broaden efficacy, but receptor balance and standardized comparative pharmacology remain essential for rational development and individualized dosing.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 10","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149271916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of Pectin-Coated Cationic Liposomes for Sustained Drug Release, Enhanced Serum Stability and Reduced Macrophage Uptake.","authors":"Plamen Simeonov, Velislava Todorova, Tsvetelina Batsalova, Balik Dzhambazov, Stanislava Ivanova, Plamen Katsarov","doi":"10.3390/pharmaceutics18101275","DOIUrl":"https://doi.org/10.3390/pharmaceutics18101275","url":null,"abstract":"<p><p><b>Background</b>: Cationic liposomes are promising carriers for anticancer agents but are often limited by rapid clearance by the mononuclear phagocyte system, poor serum stability, and insufficient control of drug release. This study aimed to develop and characterize pectin-coated, Ca²⁺-crosslinked cationic liposomes as a multifunctional delivery platform providing sustained release, enhanced serum stability, and reduced macrophage uptake while preserving the biological activity of an encapsulated anticancer compound. <b>Methods</b>: The optimal polysaccharide-to-liposome ratio was established by ζ-potential polyelectrolyte titration, and coating parameters were optimized using a Taguchi experimental design. Physicochemical characterization included dynamic light scattering (DLS), transmission electron microscopy (TEM), isothermal titration calorimetry (ITC), small-angle X-ray scattering (SAXS), and differential scanning calorimetry (DSC). The optimized formulations were further evaluated for drug release, serum stability, cellular uptake and cytotoxicity against A549 and HeLa cells using MTT and Neutral Red assays. <b>Results</b>: Polyelectrolyte titration identified a pectin-to-liposome saturation ratio of 3:1, and Taguchi optimization yielded a formulation with a drug retention efficiency of 99.34%. Pectin coating significantly reduced the initial burst release (37.9% at 1 h) and decreased cumulative drug release after 48 h (66.3%), consistent with a polymer relaxation-controlled release mechanism. The coated liposomes also exhibited enhanced serum stability and reduced macrophage uptake (up to ~73% lower in RAW264.7 cells), while maintaining uptake by non-phagocytic cells. The biological activity of the encapsulated model compound was preserved, with enhanced cancer-cell selectivity against A549 and HeLa cells demonstrated by both MTT and Neutral Red assays. <b>Conclusions</b>: Pectin-Ca²⁺ surface functionalization transforms cationic liposomes into a stable sustained-release delivery platform with reduced macrophage recognition and enhanced serum stability. These findings support the further development of this carrier as a versatile platform for the systemic delivery of anticancer agents.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 10","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149271778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}