RSC Pharmaceutics最新文献

{"title":"Redefining LNP composition: phospholipid and sterol-driven modulation of mRNA expression and immune outcomes","authors":"Muattaz Hussain, Ashish Muglikar, Danielle E. Brain, Alexander J. Plant-Hately, Neill J. Liptrott, Daragh M. McLoughlin and Yvonne Perrie","doi":"10.1039/D5PM00150A","DOIUrl":"https://doi.org/10.1039/D5PM00150A","url":null,"abstract":"<p >Ionisable lipids are essential components of lipid nanoparticles (LNPs), enabling nucleic acid encapsulation, cellular uptake, and endosomal escape. Helper lipids further modulate LNP stability, biodistribution, and intracellular trafficking. This study evaluated the <em>in vitro</em> and <em>in vivo</em> performance of LNPs incorporating different phospholipids (DSPC, DOPC, DOPE) and sterols (cholesterol, β-sitosterol), using HEK293 cells and murine models. LNPs were prepared <em>via</em> microfluidics at a fixed molar ratio (phospholipid : sterol/DOPE : SM-102 : PEG-lipid, 10 : 38.5 : 50 : 1.5 mol%). All formulations demonstrated comparable critical quality attributes, including particle size (80–120 nm), low polydispersity index (&lt;0.2), near-neutral zeta potential, and high mRNA encapsulation efficiency (&gt;95%). LNPs containing β-sitosterol exhibited significantly enhanced luciferase protein expression <em>in vitro</em> compared to the cholesterol-based control LNPs. <em>In vivo</em>, DSPC/cholesterol LNPs achieved the highest intramuscular luciferase expression, whereas DOPE-containing LNPs showed low expression. Immunisation studies showed that DOPE-containing LNPs generally enhanced total IgG and IgG1 responses, whereas IgG2a titres varied, with DOPC/DOPE highest and DSPC/DOPE lowest, indicating a disconnect between protein expression and immunogenicity. <em>Ex vivo</em> human whole blood assays revealed distinct cytokine profiles depending on sterol content. β-Sitosterol-incorporated LNPs induced elevated levels of TNF-α, GM-CSF, IL-8, IL-1β, IL-1RA, and IL-6, reflecting both pro- and anti-inflammatory activity, potentially <em>via</em> inflammasome activation. These findings demonstrate that phospholipid and sterol identity substantially influence both delivery efficiency and the quality of immune responses, emphasising the need to optimise the full lipid composition to tailor LNP performance for specific therapeutic applications.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 6","pages":" 1458-1470"},"PeriodicalIF":0.0,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d5pm00150a?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145479559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biopolymeric films based on chitosan and copaiba oleoresin: preliminary insights for oral applications","authors":"Taleessa Vieira Gomes, Ana Barbara Polo, Mariana Simões de Oliveira, Beatriz Vilela Tomé, Daphne Fonseca de Coppoli Lanferini, Laura Lima de Queiroz, Sabrina França Silva, Antonio Carlos Sant'ana, Diogo Montes Vidal, Guilherme Diniz Tavares and Ana Carolina Morais Apolônio","doi":"10.1039/D5PM00127G","DOIUrl":"https://doi.org/10.1039/D5PM00127G","url":null,"abstract":"<p >Polymeric films for oral applications remain underexplored, despite their potential as multifunctional therapeutic systems. Effective oral dressings must adhere to mucosal surfaces, promote tissue repair, reduce microbial proliferation, and protect injured areas. This study focused on the formulation and characterization of bioactive films composed of chitosan (CH) and copaiba oleoresin (COR) at varying concentrations (0.5%, 1%, and 3.5%), selected based on prior research. The films were obtained by solvent evaporation and evaluated for their physicochemical, morphological, and biological properties. Spectroscopic analyses (Raman and FT-IR) revealed molecular interactions between CH, COR, and excipients, with significant spectral shifts in functional groups, particularly from malic acid and glycerin, indicating successful incorporation.The films exhibited a moisture content ranging from 15.24% to 20.23%, which decreased with higher COR concentrations due to their hydrophobic nature. While all formulations demonstrated high swelling capacity and solubility, increased COR content reduced water absorption, suggesting a concentration-dependent modulation of film hydrophobicity. Given these findings, no single formulation emerged as universally optimal; instead, the selection of COR concentration should align with specific therapeutic goals, such as rapid bioactive release or prolonged mucosal adhesion. These results highlight the potential of CH–COR films as promising candidates for the topical treatment of oral mucosal lesions. Future research should focus on optimizing film composition to enhance antimicrobial efficacy while maintaining mechanical stability, paving the way for clinical applications.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 6","pages":" 1500-1513"},"PeriodicalIF":0.0,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d5pm00127g?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145479433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cyclodextrin-based nanosponge co-delivery of doxorubicin and EMD: synergistic anticancer activity with improved selectivity toward cancer cells","authors":"Sunisa Thongsom, Paolo Di Gianvincenzo, Giulia Ciattaglia, Ahmed Subrati, Desiré DiSilvio, Ariadna M. Birocco, Marco D'Abramo, Chanchai Boonla, Pithi Chanvorachote and Sergio E. Moya","doi":"10.1039/D5PM00183H","DOIUrl":"https://doi.org/10.1039/D5PM00183H","url":null,"abstract":"<p >Combination therapy is a promising strategy in cancer treatment aiming at improving therapeutic efficacy and overcoming tumour resistance. Cyclodextrin-based nanosponges (EpCN) were developed here for the co-delivery of doxorubicin (DX), a hydrophilic chemotherapeutic agent, alongside <em>N</em>,<em>N</em>-bis (5-ethyl-2-hydroxybenzyl) methylamine (EMD), a hydrophobic compound targeting c-Myc. EpCNs were synthesized by crosslinking β-cyclodextrin with epichlorohydrin, then DX and EMD were loaded either separately or together into the nanosponge. The nanosponges were extensively characterized combining Dynamic Light Scattering (DLS), Atomic Force Microscopy (AFM), Scanning Electron Microscopy (SEM) and Nuclear Magnetic Resonance (NMR). The dual-loaded nanosponges with DX and EMD (DX/EMD-EpCN) displayed uniform sizes (30 ± 13 nm), high encapsulation efficiency (&gt;98%), a zeta potential of +23 ± 4 mV, and a pH-responsive drug release, with faster release at acidic pH mimicking tumour conditions. <em>In vitro</em> studies were carried out on cancerous (A549 and MCF-7) and non-cancerous (WI-38) cells to explore the therapeutic potential of the drug-loaded EpCNs. Cytotoxicity results demonstrated that DX/EMD-EpCNs significantly reduced cell viability, more than free drugs or single drug-loaded EpCNs in both cancerous cell lines. The therapeutic potential of combining DX and EMD was improved by the encapsulation into EpCN, as indicated by a strong synergism (combination index: &lt;0.6), with a reduced effective dose, and improved drug uptake in cancer cells while sparing normal cells. Cell cycle analysis reveals that DX/EMD-EpCNs induced multi-phase arrest at the G0/G1 and G2/M phases, leading to a superior apoptotic induction as confirmed by the annexin V/Zombie UV staining. Western blot analysis demonstrated that the DX/EMD-EpCN significantly suppressed c-Myc and Bcl-2 expression while increased cleaved-PARP expression in both cancer cell lines, indicating the activation of caspase-dependent apoptosis. In contrast, the downregulation of c-Myc and Bcl-2 by single drug-loaded EpCNs altered cell cycle progression but did not significantly induced apoptosis. The co-delivery of DX and EMD by EpCNs enhanced therapeutic potency through various mechanisms. These findings highlight the potential of cyclodextrin-based nanosponges as a versatile drug delivery platform for combination chemotherapy profiting from their capability of simultaneously encapsulating both hydrophilic and hydrophobic drugs.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 6","pages":" 1514-1532"},"PeriodicalIF":0.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d5pm00183h?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145479434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring hot melt extrusion in the formation of exemestane/amino acid co-amorphous systems","authors":"Ioannis Partheniadis, Maria Tsouka and Ioannis Nikolakakis","doi":"10.1039/D5PM00146C","DOIUrl":"https://doi.org/10.1039/D5PM00146C","url":null,"abstract":"<p >Co-amorphous systems (CAMS) of exemestane (EXE) were prepared with three amino acid (AA) co-formers of increasing hydrophobicity: (i) <small>L</small>-lysine (LYS), (ii) <small>L</small>-valine (VAL) and (iii) <small>L</small>-methionine (MET) using feed solvent pretreatment hot-melt extrusion (mHME). Thermal analysis (DSC and TGA) guided processing parameters confirmed the class III glass-forming ability of EXE (<em>T</em><small>_g</small> = 91.2 °C). Hansen solubility parameters (Δ<em>δ</em><small>_t</small> &lt; 4 MPa<small>^1/2</small>) predicted favorable drug/co-former miscibility. PXRD and DSC demonstrated successful co-amorphization for molar ratios of EXE/LYS (1 : 1 and 1 : 2), EXE/MET (1 : 1) and EXE/VAL (2 : 1 drug/AA). ATR-FTIR indicated co-amorphization predominantly by simple molecular mixing with only weak interactions. The physical stability of CAMS was evaluated by isothermal microcalorimetry, dynamic mechanical analysis (DMA) and crystallographic profiles (pXRD) obtained at different times during accelerated stability tests (40 °C, 75% RH). EXE/LYS systems exhibited the longest relaxation times (<img>), translating as excellent physical stability, which corroborated the results of accelerated tests. EXE/MET showed moderate stabilization, while EXE/VAL was the least stable. Under non-sink conditions of the dissolution test, EXE/LYS (1 : 1) presented a pronounced spring–parachute profile with sustained supersaturation, outperforming other EXE/AA CAMS.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 6","pages":" 1533-1544"},"PeriodicalIF":0.0,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d5pm00146c?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145479435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug release from binary and ternary flexible dose combinations manufactured by drop-on-demand impregnation of mesoporous silica tablets","authors":"Zuzana Hlavačková, David Zůza, Erik Sonntag, Jakub Petřík, Ondřej Dammer and František Štěpánek","doi":"10.1039/D5PM00070J","DOIUrl":"https://doi.org/10.1039/D5PM00070J","url":null,"abstract":"<p >Fixed-dose drug combinations (FDC) such as bi-layer tablets are known to improve treatment outcomes in polypharmacy patients thanks to better medication adherence achieved by reduced pill burden. However, the bulk manufacturing of FDCs is technically and economically viable only for such combinations where a sufficiently large patient cohort exists. The present work explores the “flexible dose combination” approach, which is based on the bulk manufacturing of placebo tablets containing mesoporous silica particles, and their subsequent impregnation by a combination of active pharmaceutical ingredients (API) at dosage strengths that can be adjusted to smaller patient cohorts or even individual patients. The present approach is based on volumetric dosing, which is generally faster and allows finer dosing steps than powder-based additive manufacturing methods. Specifically, this study investigates the potential of mesoporous silica-based tablets for the commonly prescribed triple combination of candesartan, hydrochlorothiazide, and amlodipine. Two grades of mesoporous silica were compared in terms of drug loading capacity and release kinetics for each API individually, and their binary and ternary combinations. Tablets containing Syloid 72FP showed superior performance in terms of drug release rates than tablets with custom-made mesoporous silica. The order in which the APIs were impregnated was found to be an important factor influencing drug release kinetics. The loading sequence candesartan–hydrochlorothiazide–amlodipine emerged as the best performing, enhancing amlodipine release and maintaining high release rates of hydrochlorothiazide and candesartan when compared to nanocomponent benchmarks. The findings prove that mesoporous placebo tablets loaded by the drop-on-demand method can effectively accommodate the triple drug combination, demonstrating their potential as a carrier system for flexible-dose formulations. At the same time, non-trivial API-specific dependence of drug release on the quantity and order of drug loading into the tablet was found, which must be considered when designing such formulations.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 6","pages":" 1447-1457"},"PeriodicalIF":0.0,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d5pm00070j?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145479558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances in biomedical applications of smart nanomaterials: a comprehensive review","authors":"Manoj Kumar Goshisht, Ashu Goshisht, Animesh Bajpai and Abhishek Bajpai","doi":"10.1039/D5PM00137D","DOIUrl":"https://doi.org/10.1039/D5PM00137D","url":null,"abstract":"<p >Smart nanomaterials (NMs) have emerged as a transformative tool in the biomedical field owing to their distinct physicochemical properties and multifunctional abilities. In this comprehensive review, we have featured the current advancements in utilization of smart NMs in four critical domains of biomedical science: (i) wound healing, (ii) cancer theranostics, (iii) tissue engineering and regeneration, and (iv) nanotoxicity assessment. In section 3, we have discussed the wound healing applications of metallic and non-metallic smart NMs in controlled drug delivery, rapid tissue repair/regeneration, and antimicrobial properties in synergism with photodynamic and photothermal therapy. Section 4 encompasses recent breakthroughs in cancer theranostics that leverage the dual functionality of smart NMs for simultaneous diagnosis and therapy. Nanocarriers designed with imaging agents and therapeutic payloads enable targeted drug delivery along with a reduction in side effects and improvement in treatment efficacy. The integration of stimulus-responsive mechanisms, such as pH and temperature sensitivity, further enhances their theranostic potential. Section 5 underscores NM-based efficient scaffolds and 3-dimensional (3D) bioprinting strategies to boost tissue engineering and regeneration by delivering growth factors, genetic materials, and bioactive chemicals. Section 6 encompasses recent breakthroughs in nanotoxicity assessment through <em>in vitro</em>, <em>in vivo</em>, and <em>in silico</em> approaches. The section also includes key toxicity mechanisms and challenges of smart nanomaterials in clinical translation.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 6","pages":" 1227-1267"},"PeriodicalIF":0.0,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d5pm00137d?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145479523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preliminary evidence for the combined efficacy of focused ultrasound blood–brain barrier opening and Re-1 delivery for anxiety and memory improvement in a 3xTg-Alzheimer's disease mouse model","authors":"Rebecca L. Noel, Samantha L. Gorman, Alec J. Batts, Despoina Tsakri, Daniella A. Jimenez, Maria Pelecanou, Marina Sagnou and Elisa E. Konofagou","doi":"10.1039/D5PM00059A","DOIUrl":"https://doi.org/10.1039/D5PM00059A","url":null,"abstract":"<p >The aim of this preliminary study is to evaluate the efficacy of early intervention with Focused Ultrasound-induced Blood–Brain Barrier Opening (FUS-BBBO) and <strong>Re-1</strong> delivery for anxiety amelioration, memory improvement, and pathology reduction in an Alzheimer's Disease (AD) mouse model. FUS-BBBO was applied and <strong>Re-1</strong> delivered to the hippocampi of presymptomatic, male triple transgenic (3xTg)-AD mice using a preventative paradigm of 10 total biweekly treatments over the course of 5 months. Following treatment, the animals underwent five days of behavioral testing for anxiety, spatial memory, and reversal learning. The combination of FUS-BBBO and <strong>Re-1</strong> delivery showed evidence of improving the long-term spatial memory and short-term reversal learning with no significant effect on amyloid and tau accumulation. The small sample size is a limiting factor for this preliminary study, which still offers promising indications in support of early intervention with amyloid-targeting <strong>Re-1</strong> and FUS-BBBO for cognitive and minor pathological improvement in AD.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 1","pages":" 60-66"},"PeriodicalIF":0.0,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2026/pm/d5pm00059a?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146049311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ion pairing as a strategy to enhance the delivery of diclofenac","authors":"Mignon Cristofoli, Jonathan Hadgraft, Majella E. Lane and Bruno C. Sil","doi":"10.1039/D5PM00096C","DOIUrl":"https://doi.org/10.1039/D5PM00096C","url":null,"abstract":"<p >This study explores the use of ion pairing and solvent selection to enhance the percutaneous delivery of diclofenac (DF) from topical formulations. Previous investigations identified <small>L</small>-histidine monochloride monohydrate (LHSS) as an ion pair candidate for diclofenac sodium (DNa). Initial <em>in vitro</em> permeation tests (IVPT) demonstrated that while LHSS increased DF permeation, it caused DF precipitation at higher concentrations. As DNa is sparingly soluble in water, the only solvent in which LHSS dissolves, its solubility was tested in alternative solvents. The highest solubility was observed in Transcutol® (TC), dipropylene glycol (DiPG) and propylene glycol (PG). Building on earlier research using TC : water binary systems to evaluate ion pairs, this study assessed: (i) the substitution of TC with DiPG in binary formulations, (ii) the development of ternary systems comprising water, TC and either DiPG or PG, and (iii) their impact on DF delivery using finite dose IVPT with porcine skin. The inclusion of LHSS (10 mg mL<small>⁻¹</small>) with DNa (10 mg mL<small>⁻¹</small>) in a DiPG : water (60 : 40 v/v) binary system significantly enhanced DF delivery (2.69 ± 1.01%), relative to the LHSS-free control (1.02 ± 0.44%, <em>p</em> &lt; 0.05.). However, this was significantly lower than in TC : water binary formulations (4.80 ± 1.08–5.41 ± 2.21%; <em>p</em> &lt; 0.05). Similarly, the ternary formulation containing DiPG (5 mg mL<small>⁻¹</small> DNa; 12.5 mg mL<small>⁻¹</small> LHSS; DiPG : TC : water; 10 : 40 : 50 v/v/v) resulted in lower DF delivery (5.62 ± 2.78%) compared to the corresponding TC : water (50 : 50 v/v) binary formulation (12.26 ± 3.06%, 5 mg mL<small>⁻¹</small> DNa; 12.5 mg mL<small>⁻¹</small> LHSS, <em>p</em> &lt; 0.05). Conversely, replacing DiPG with PG in the ternary formulation (PG : TC : water; 10 : 40 : 50 v/v/v) containing 25 mg mL<small>⁻¹</small> LHSS, significantly enhanced DF permeation (4.26 ± 1.41 μg cm<small>⁻²</small>) compared to all binary (0.14 ± 0.28–1.52 ± 0.32 μg cm<small>⁻²</small>) and ternary formulations (0.21 ± 0.36–1.72 ± 1.06 μg cm<small>⁻²</small>, <em>p</em> &lt; 0.05). This formulation also outperformed a recognised commercial product (1.74 ± 0.6 μg cm<small>⁻²</small>) by 145%, despite containing only half the DNa concentration and resulted in the highest total DF uptake as a percentage of the applied dose (27.25 ± 2.61%). This work builds on previous findings, confirming that LHSS enhances DF delivery in combination with DNa. By examining solvent systems and counterion effects, it provides a deeper understanding of formulation strategies to optimise the percutaneous delivery of DF.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 5","pages":" 1163-1174"},"PeriodicalIF":0.0,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d5pm00096c?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145073485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and evaluation of N-acetyl cysteine-grafted polyamidoamine dendrimers for enhanced brain delivery of donepezil hydrochloride","authors":"Teeja Suthar and Keerti Jain","doi":"10.1039/D5PM00119F","DOIUrl":"https://doi.org/10.1039/D5PM00119F","url":null,"abstract":"<p >Donepezil hydrochloride (DPZ) is a USFDA-approved, selective and non-competitive, centrally acting acetylcholinesterase inhibitor used for the clinical management of dementia associated with mild-to-moderate Alzheimer's disease (AD). However, treatment with DPZ is usually associated with various peripheral adverse effects, which necessitate the use of ligand-mediated targeted delivery approaches for selective delivery to the target site. This study reports the synthesis and evaluation of <em>N</em>-acetyl cysteine (NAC)-conjugated poly(amidoamine) G4 (PAMAM G4) dendrimers for brain-targeted delivery of DPZ. Fourier-transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopy were used to confirm the conjugation of NAC to PAMAM G4 dendrimers. DPZ was loaded onto PAMAM G4 and the NAC-G4 conjugate, and % drug entrapment, loading efficiency, and release behavior were determined. The cell viability assay showed enhanced viability with DPZ on incorporation into the NAC-G4 conjugate. Furthermore, we observed a higher peak plasma concentration and mean residence time of DPZ from the dendrimeric conjugate in pharmacokinetic studies. The DPZ-loaded ligand-conjugated dendrimeric conjugate holds promise as a potential strategy for the treatment of AD.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 6","pages":" 1489-1499"},"PeriodicalIF":0.0,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d5pm00119f?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145479432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unlocking the potential of exosomes ‘extracellular vesicles’: drug delivery advancements and therapeutics in ocular diseases","authors":"Nagendra Verma, Swati Arora, Anurag Kumar Singh and Jahangir Ahmed","doi":"10.1039/D5PM00097A","DOIUrl":"https://doi.org/10.1039/D5PM00097A","url":null,"abstract":"<p >Overcoming the ocular barriers, such as the corneal, blood-retinal, and conjunctival membranes, poses a significant challenge in ophthalmic drug delivery and therapy. These barriers serve a natural protective function and limit drug access into the eye. In recent years, interest has increasingly centered on exosomes, a subclass of extracellular vesicles with a diameter of 30 to 150 nm. Encapsulated within a lipid bilayer, exosomes naturally carry a variety of bioactive molecules, including proteins, lipids, and nucleic acids, and play a crucial role in cell–to–cell communication and pathophysiology. Nonetheless, their ability to transfer cargos (proteins, lipids, and nucleic acids) to recipient cells provides an exclusive approach to the delivery of various therapeutic agents, such as small molecules or nucleic acid drugs, to target ocular tissues due to their remarkable biocompatibility, stability, low toxicity, and minimal immunogenicity. This review aims to discuss the research in progress on the advantages of exosome-guided drug delivery and ongoing clinical trials for ocular diseases and therapy. This work aspires to bridge the gap between bench research and clinical application, fostering treatments that remarkably enhance patient outcomes in ocular disorders.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 6","pages":" 1201-1226"},"PeriodicalIF":0.0,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d5pm00097a?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145479522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}