Molecular Pharmaceutics最新文献

{"title":"Presence of Different Ceramide Species Modulates Barrier Function and Structure of Stratum Corneum Lipid Membranes: Insights from Molecular Dynamics Simulations.","authors":"Moritz Reuter, Edwin Joseph, Guoping Lian, Dominique J Lunter","doi":"10.1021/acs.molpharmaceut.5c00580","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c00580","url":null,"abstract":"<p><p>Ceramides, as major components of the human stratum corneum's (SC) lipid matrix, are considered crucial for regulating the skin's barrier function against the ingress of exogenous substances as well as to prevent water loss through the skin. Multiple clinical and experimental studies found different classes of ceramide species to affect the skin barrier nonuniformly, with some ceramides being associated with an impaired skin barrier, such as ceramide NS, while others are associated with a healthy, unimpaired skin, e.g., ceramide NP. This study investigates how the presence of these two ceramide classes in an SC lipid bilayer membrane influences the water permeability as well as the structure of the bilayer using molecular dynamics (MD) simulations. To this end, simulated membranes comprising free fatty acids, cholesterol, as well as either ceramide NS or ceramide NP were systematically compared in regard to differences in the membrane structure and water permeability, as well as to results found in the literature. The simulation found ceramide NP-containing membranes to have a significantly lower water permeability than ceramide NS-containing systems, with the permeability values of NP-based systems being almost half of those of the NS-based systems. Furthermore, the simulation also showed significant structural differences between the two systems in terms of headgroup conformation and lipid positioning in the membrane, hinting toward the molecular mechanisms underpinning the differences in permeability of the two systems. In conclusion, the MD simulation was able to reproduce effects of the presence of different ceramide species in the membrane that are consistent with experimental as well as clinical studies on skin barrier function and drug delivery and validate previous simulation-based investigations into SC lipid bilayer permeability.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Intranasal Fisetin-Loaded Mucoadhesive Microemulsion for Schizophrenia Management: A Nanotherapeutic Approach to Enhance Brain Bioavailability and Improved Efficacy.","authors":"Tamizmaran V, V S Mannur, Rahul Koli, Prakash Biradar","doi":"10.1021/acs.molpharmaceut.5c00584","DOIUrl":"10.1021/acs.molpharmaceut.5c00584","url":null,"abstract":"<p><p>Schizophrenia, a complex neuropsychiatric disorder originating in the central nervous system, poses significant therapeutic challenges primarily due to the restrictive nature of the blood-brain barrier (BBB). In this study, a fisetin-loaded mucoadhesive microemulsion (fisetin-MME) was successfully developed and optimized via Box-Behnken Design (BBD) to enhance the solubility and brain-targeting potential of fisetin following intranasal administration. The optimized formulation exhibited a mean droplet size of 64.0 nm ± 0.05, a polydispersity index (PDI) of <0.5, and high entrapment efficiency (94.9%), alongside favorable thermodynamic stability, rheological characteristics, and mucoadhesive strength (3.24 ± 0.95 g). Physicochemical characterization by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier-transform infrared spectroscopy (FT-IR), and transmission electron microscopy (TEM) confirmed the structural integrity and compatibility of the formulation. A validated reverse-phase high-performance liquid chromatography (RP-HPLC) method consistently quantified fisetin with a retention time of 6.01 ± 0.23 min. The fisetin-MME demonstrated enhanced <i>in vitro</i> release (85.2 ± 2.345%) and <i>ex vivo</i> nasal mucosal permeation (87.6 ± 0.25%), with significantly improved flux (40.23 ± 0.06 μg/cm²/h) and permeability coefficient (81.23 × 10^-6 cm/s), indicating efficient transmucosal transport. Pharmacokinetic evaluation revealed a marked improvement in both systemic and brain bioavailability following intranasal administration, with a brain C_max of 261.53 ± 0.14 ng/g and AUC₀-t of 2564.0 ± 232.0 h·ng/g, surpassing the reference standard (C_max of 228.50 ± 0.36 ng/g; AUC₀-t of 2257.6 ± 245.9 h·ng/g). Behavioral assessments, including the Forced Swim Test and Balance Beam Test, demonstrated significant amelioration of schizophrenia-like symptoms, including hyperlocomotion, catalepsy, and impaired motor coordination, with fisetin-MME showing superior neuroprotective and antidepressant effects compared to the standard drug by Day 14 (<i>p</i> < 0.001). Histopathological analysis further supported these findings, demonstrating marked neuroprotective effects in the cortical and hippocampal regions, as evidenced by reduced neuronal degeneration and attenuation of neuroinflammatory markers. These results highlight the potential of intranasally delivered fisetin-MME as a promising nanotherapeutic strategy for the management of schizophrenia.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thermodynamic Perspectives on the Impact of a Second Drug on Amorphous Drug Solubility.","authors":"Shun Kaneko, Keisuke Ueda, Rei Hakata, Kenjirou Higashi, Masataka Ito, Shuji Noguchi, Kunikazu Moribe","doi":"10.1021/acs.molpharmaceut.5c00345","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c00345","url":null,"abstract":"<p><p>Drug amorphous solubility can be changed in the presence of other compounds, making it essential to elucidate the underlying mechanisms for designing supersaturated formulations. In this study, we experimentally determined how a second drug affects the amorphous solubility of ritonavir (RTV) and analyzed these effects from a thermodynamic perspective. Lopinavir (LPV), cilnidipine (CND), and probucol (PBC) were used as second drugs. The coexistence of each second drug in an aqueous solution reduced the amorphous solubility of RTV. In the presence of LPV and CND, the experimentally determined RTV amorphous solubility was close to the value predicted under the assumption of ideal mixing of RTV and second drugs. In contrast, in the presence of PBC, the experimentally determined RTV amorphous solubility exceeded the predicted value. Dynamic vapor sorption (DVS) measurements revealed that the RTV/LPV coamorphous absorbed water similarly to amorphous RTV. Conversely, water absorption in the RTV/CND and RTV/PBC coamorphous decreased compared with amorphous RTV. Using the experimentally determined amorphous solubilities and water absorption data, the interaction parameters between RTV and each second drug within the water-saturated drug-rich phase were calculated. The absolute value of the interaction parameter in the RTV/LPV system is relatively small, suggesting that incorporating LPV into the RTV-rich phase had minimal impact on water absorption and drug-drug interaction strength in the RTV-rich phase, resulting in experimentally determined solubility values that align closely with those predicted by ideal mixing of RTV and LPV. Meanwhile, the interaction parameters of the RTV/CND and RTV/PBC systems were negative, indicating relatively strong drug-drug interactions that can further reduce RTV amorphous solubility. However, for these two systems, the mixing of second drugs also decreased the water content in the RTV-rich phase, which would mitigate the extent of the solubility reduction. In the RTV/CND system, the strong drug-drug interaction and reduced water content largely offset each other. This results in an experimentally determined RTV amorphous solubility similar to the value predicted by the ideal mixing of RTV and CND. In contrast, in the RTV/PBC system, the water content of the RTV-rich phase was more substantially decreased, leading to a higher experimentally determined value of RTV amorphous solubility than that predicted by ideal mixing of RTV and PBC. Overall, this study elucidates the impact of a second drug on the amorphous solubility of a primary drug and provides valuable insights for the design of supersaturated formulations containing multiple drugs.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intranasal Therapeutics for Neurodegenerative Disorders: Overcoming the Blood-Brain Barrier with Smart Formulations and Devices.","authors":"Siddhant Kumar, Akshay Yadav, Rahul K Verma, Akhilesh Kumar, Piyush Kumar Gupta, Rahul Shukla","doi":"10.1021/acs.molpharmaceut.5c00386","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c00386","url":null,"abstract":"<p><p>Neurodegenerative diseases have always posed a significant therapeutic challenge due to the restrictive nature of the blood-brain barrier (BBB). Intranasal drug delivery has emerged as a noninvasive approach to bypass the BBB, enabling targeted brain drug delivery while improving drug retention and transport. This review explores the physiological basis of the nose-to-brain pathway and various formulation strategies including mucoadhesive systems, permeation enhancers, and magnetophoretic approaches. Additionally, strategies to enhance intranasal delivery, such as P-glycoprotein inhibitors, cell-penetrating peptides, and enzyme inhibitors, are discussed alongside nanotechnology-based carriers, including surface-modified and bioconjugated systems. The role of specialized intranasal drug delivery devices (e.g., ViaNase, Optimist, and SipNose) in enhancing precision dosing is also highlighted. Despite its promise, intranasal delivery faces challenges such as limited therapeutic windows, scalability issues, and the constraint of the nasal cavity volume, which can accommodate only 200 μL of liquid per nostril. Optimizing drug stability, achieving accurate dosing, and enhancing bioavailability without nasal irritation remain key hurdles. Future research should focus on the development of commercially feasible nanoformulations and innovative medical devices to improve drug targeting and treatment efficacy for patients with neurodegenerative diseases.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peptide-Based PET Imaging Differentiates Netrin-1 Expression in Tumors.","authors":"Jingwen Wang, Lixia Feng, Xingru Long, Hao Yang, Li Zhang, Wenzhu Hu, Haibo Chen, Dawei Jiang, Yongsheng Zhao, Shu Hu, Xiaoli Lan, Wei Cao","doi":"10.1021/acs.molpharmaceut.5c00339","DOIUrl":"10.1021/acs.molpharmaceut.5c00339","url":null,"abstract":"<p><p>Neuroaxonal guidance factor-1 (Netrin-1) is a secreted glycoprotein overexpressed in cancer. It promotes tumor growth and metastasis and has demonstrated potential as a biomarker for tumor theranostics. In this study, we developed a novel Ga-68 labeled peptide radiotracer, termed [⁶⁸Ga]Ga-DKP, to assess the expression of netrin-1 in tumors. The tracer exhibited high radiochemical purity (over 95%) and strong stability. In vitro cellular assays demonstrated that A549 and 4T1 cells exhibited stronger binding capabilities for the probe than those in A375 cells, as they expressed higher levels of netrin-1. Furthermore, a blocking assay in A549 cells confirmed the affinity and specificity of the probe for netrin-1. In vivo PET/CT imaging and biodistribution studies demonstrated rapid tumor uptake and tissue excretion. A549 and 4T1 tumor-bearing mice showed higher tumor-to-muscle ratios (9.70 ± 1.24 and 10.94 ± 3.44, respectively) at 2 h postinjection, which were approximately 3-fold higher than A375 tumors. In conclusion, [⁶⁸Ga]Ga-DKP could be used to quantify netrin-1 levels, showing potential for clinical application.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Voices in <i>Molecular Pharmaceutics</i>: Meet Dr. Sasha Ebrahimi, Manipulator of Molecules and Designer of Drug Delivery Systems to Enhance the Effectiveness of Therapeutics.","authors":"Sasha B Ebrahimi","doi":"10.1021/acs.molpharmaceut.5c00889","DOIUrl":"10.1021/acs.molpharmaceut.5c00889","url":null,"abstract":"","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AIoptamer: Artificial Intelligence-Driven Aptamer Optimization Pipeline for Targeted Therapeutics in Healthcare.","authors":"Tushar Gupta, Priyanka Sharma, Sheeba Malik, Pradeep Pant","doi":"10.1021/acs.molpharmaceut.5c00343","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c00343","url":null,"abstract":"<p><p>Aptamers are short, single-stranded DNA or RNA molecules known for their high specificity and affinity toward target biomolecules, making them powerful tools in drug discovery, diagnostics, and biosensing. However, conventional aptamer selection methods such as SELEX (Systematic Evolution of Ligands by EXponential Enrichment) are often labor-intensive, time-consuming, and resource-demanding. To overcome these limitations, we introduce a novel AI-driven aptamer optimization pipeline (AIoptamer: AI-driven optimization of aptamers) that integrates artificial intelligence with advanced classical computational approaches to accelerate aptamer discovery and design. The workflow begins with a known aptamer-host complex and systematically generates all possible aptamer sequence variants to target the same host. These variants are then screened using AI-based models that rank them based on sequence features and predicted binding affinity. Top candidates undergo structural modeling through CHIMERA_NA, an in-house mutagenesis tool designed to perform structural mutations in nucleic acids. The modeled structures are further evaluated using PredPRBA, a deep learning-based scoring function tailored for RNA-protein binding affinity prediction and PDA-Pred, a machine learning based model for predicting DNA-protein binding affinity. The highest-ranking aptamer-host complexes are then refined through molecular dynamics (MD) simulations to assess structural stability and interaction strength at the atomic level. Our pipeline demonstrates effectiveness across both RNA and DNA aptamer complexes, offering a generalized and robust framework for aptamer optimization. By combining AI-powered prediction with conventional computational techniques, our method advances the rational design of aptamers and significantly reduces reliance on traditional experimental trial-and-error strategies, making aptamer optimization faster, scalable and more efficient.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug Delivery Mechanisms of Poly(glycerol sebacate): An In-Depth Study of the Energetics at the Molecular Scale.","authors":"Xavier Davoy, Julien Devémy, Pierre Fayon, Philip Chennell, Mehdi Sahihi, Sébastien Garruchet, Alain Dequidt, Patrice Hauret, Patrice Malfreyt","doi":"10.1021/acs.molpharmaceut.5c00102","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c00102","url":null,"abstract":"<p><p>Molecular simulations were carried out to investigate the mechanisms of drug delivery from poly(glycerol sebacate) (PGS). We simulated a number of key stages, from the encapsulation of the active pharmaceutical ingredients (API) in bulk PGS to their release into the water phase through the adsorption processes on the PGS surface. Caffeine, paracetamol, and ibuprofen were the studied APIs. Each stage of the API release was characterized by the calculation of a free energy property related to absorption, adsorption, or association. The free energy of absorption showed that the PGS material is able to accommodate APIs of different polarities and hydration properties due to the presence of hydrophobic and hydrophilic regions in the material. The free energy values of adsorption of the APIs on the PGS surface remain favorable, whereas the free energies of binding between APIs and glycerol, sebacic acid, and prepolymer molecules are weaker, thus indicating a possible release of the APIs into water from an energy viewpoint.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Permeation Enhancers on the Release of Insulin from Tablets in Biorelevant Media.","authors":"Andrew Fagan, Lorraine M Bateman, Abina M Crean, Joseph P O'Shea, Lynne S Taylor","doi":"10.1021/acs.molpharmaceut.5c00249","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c00249","url":null,"abstract":"<p><p>The use of chemical permeation enhancers (PEs) to improve the permeation of peptides across gastric and intestinal epithelia has proven an effective strategy in the development of oral dosage forms of peptides. However, there remains a poor understanding of how the presence of PEs impacts the dissolution characteristics of oral formulations containing peptides, nor is it known how the complex composition of biological media can influence their behavior <i>in vivo</i>. This investigation sought to examine the effect of two widely studied PEs, sodium caprate (C10) and salcaprozate sodium (SNAC), on the release behavior of a model peptide, insulin, from minitablets in a variety of biorelevant media. First, the equilibrium solubilities of insulin, C10, and SNAC were determined in simulated gastric and intestinal media. Insulin, C10, and SNAC all displayed pH-dependent solubility across a physiologically relevant range of pH conditions. Moreover, at high concentrations, C10 was found to overwhelm the buffer capacity of the simulated media, increasing the pH of fasted state simulated intestinal fluid (FaSSIF) from 6.5 to 9.0, fed state simulated intestinal fluid (FeSSIF) from pH 5.0 to 8.8 and fasted state simulated gastric fluid (FaSSGF) from pH 1.6 to 9.2. Similarly, SNAC caused an increase in the pH of FaSSIF from 6.5 to 7.9, FeSSIF from pH 5.0 to 7.7, and FaSSGF from pH 1.6 to 7.6. Relative to in simulated intestinal media, the solubility of insulin was found to increase significantly in media at pH representative of saturated C10 and SNAC solutions, increasing from 0.1 mg/mL in blank FaSSIF to 14.0 mg/mL in phosphate buffer at pH 7.6 and to 23.7 mg/mL in phosphate buffer at pH 9.2, suggesting that the presence of C10 and SNAC at high concentrations could have a considerable favorable impact on insulin solubility. Furthermore, the release profiles of insulin from minitablets containing C10 and SNAC were investigated in each of the biorelevant media and compared with the release profiles of insulin from blank minitablets in the absence of PEs. Insulin release from the blank minitablets was found to be media dependent, following an apparent solubility trend. Complete release of insulin was observed in simulated gastric media; however, only between 67 and 82% release was observed in the simulated intestinal media. On the other hand, on the addition of C10 and SNAC to the formulation, greater than 90% release was observed across all media investigated. This difference in release behavior was determined to be caused by an increase in pH at the surface of the minitablets due to the presence of high local concentrations of C10 and SNAC, respectively, as confirmed by a change in color of a universal indicator solution. These findings offer a key insight into the influence that C10 and SNAC have on the dissolution characteristics of insulin from an oral dosage form in a variety of simulated gastric and intestinal media.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intermolecular Dynamics of Monoglyceride Mesophases with Their Biomacromolecular Corona.","authors":"Wye-Khay Fong, Dimitri Vanhecke, Daniel Hauser, Sandor Balog, Philipp Lemal, Shiva Montasseri, Barbara Rothen-Rutishauser, Alke Petri-Fink","doi":"10.1021/acs.molpharmaceut.5c00435","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c00435","url":null,"abstract":"<p><p>Advances in the development of lipid nanoparticles have resulted in delivery systems that both protect the encapsulated drug and improve therapeutic outcomes. When introduced in vivo, nanoparticles are rapidly covered by a biomolecular corona, influencing their biological fate, i.e., interaction with cells, uptake, and intracellular fate. This study explores the interactions between nonlamellar lipidic drug delivery systems and non-lipolytic components of complex cell culture media, focusing on the dynamic formation of the corona and its effects on the lipid nanoparticle behavior. Monoglyceride formulations were monitored for changes in nanostructure and particle size, and mechanisms for these changes were elucidated. Not only do these biomacromolecules influence the size and structure of the nanoparticles themselves, but they can simultaneously diffuse into the mesophase nanostructure. The study highlights that lipid nanoparticles undergo dynamic changes in physiological conditions influenced by adsorbed proteins and other nondegradative components in complex cell culture media, separate from effects caused by lipases or other enzymatic factors. These induced structural transformations can significantly alter the nanoparticles' physical properties and drug release profiles, potentially causing deviation from their intended therapeutic performance. Understanding these interactions is thus crucial for optimizing the design and functionality of lipid-based drug delivery systems in biomedical applications.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}