RSC Pharmaceutics最新文献

Quercetin, a naturally occurring flavonoid, exerts potential pharmacological and therapeutic effects, primarily due to its antioxidant properties and ability to mitigate cognitive impairment. However, its inadequate bioavailability, poor absorption, and rapid clearance limit its therapeutic efficacy. To overcome these limitations, we developed organically modified silica (ORMOSIL) nanoparticles conjugated with lactoferrin (LF), a glycoprotein renowned for its ability to cross the blood–brain barrier and exert neuroprotective effects. This scaffold aims to enhance quercetin delivery to the brain, ultimately improving therapeutic outcomes. This study employed a multi-faceted approach, involving the detailed characterization of nanoparticles, and in vivo assessment using a rat model to evaluate cognitive functions after scopolamine-induced amnesia. Behavioral tests, biochemical assessment, potential to inhibit the acetylcholinesterase enzyme, and histological findings collectively indicate improved efficacy of LF-Q-ORMOSIL compared to quercetin and ORMOSIL alone in an acute study. Furthermore, in vivo and ex vivo biodistribution patterns suggest better retention and increased brain targeting of the LF-conjugated formulation in the brain. Our findings demonstrate that LF-Q-ORMOSIL holds promise for enhanced delivery and therapeutic efficacy in mitigating cognitive deficits associated with neurodegenerative processes.

Psoriasis is a long-term autoimmune disorder that causes an excessive growth of keratinocytes in the skin. A mix of immune system irregularities, environmental influences, and genetic predisposition triggers it. The condition significantly impacts the quality of life of those affected. Histopathological investigation and clinical evaluation are two of the current diagnostic techniques; One method used to assess the severity of psoriasis is the Psoriasis Area and Severity Index (PASI). Topical medications and systemic therapy are examples of traditional treatments; nevertheless, they frequently do not offer long-lasting comfort and may have unfavourable side effects. Recent developments in targeted psoriasis therapy highlight the potential of microneedle technology, particularly nanoparticulate microneedle formulations, which allow improved drug administration and decreased systemic toxicity. Further, incorporating artificial intelligence (AI) and machine learning (ML) into microneedle-based formulations is rising as a powerful tool to predict optimal design parameters, mechanical properties, and drug release profiles, thereby speeding research and enhancing therapeutic precision. This review delves into the pathophysiology, diagnosis, and treatment of psoriasis, focusing on novel microneedle approaches and AI, ML-based optimisation. We also examined ongoing studies, treatment patterns, and regulatory issues. We highlight patents about microneedles and how they could revolutionise the way psoriasis is treated.

Chitosan is a widely applied polysaccharide in different fields due to its versatility, biocompatibility and low toxicity. Its structure possesses reactive functional groups that can be modified without involving the chain backbone, which improves its physicochemical and biochemical properties. Several chemical modifications such as alkylation, acylation, thiolation, and grafting with polymers and active molecules can be combined with various supramolecular chemistry approaches such as crosslinking, self-assembly, polyelectrolyte-complex formation, ionic gelation, and polymerization to formulate chitosan-based nano-objects that can encapsulate many active pharmaceutical ingredients, eventually enabling new applications of chitosan in the pharmaceutical, biomedical and biotechnological fields. This review summarizes the critical findings of some recent works published in the last years on the chemical modification of chitosan; the design of chitosan-based nano-objects for the encapsulation and controlled delivery of active pharmaceutical ingredients; and the biodistribution, biodegradation and toxicology of the nano-objects.

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 in vitro and in vivo performance of LNPs incorporating different phospholipids (DSPC, DOPC, DOPE) and sterols (cholesterol, β-sitosterol), using HEK293 cells and murine models. LNPs were prepared via 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 (<0.2), near-neutral zeta potential, and high mRNA encapsulation efficiency (>95%). LNPs containing β-sitosterol exhibited significantly enhanced luciferase protein expression in vitro compared to the cholesterol-based control LNPs. In vivo, 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. Ex vivo 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 via 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.

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.

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 N,N-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 (>98%), a zeta potential of +23 ± 4 mV, and a pH-responsive drug release, with faster release at acidic pH mimicking tumour conditions. In vitro 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: <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.

Co-amorphous systems (CAMS) of exemestane (EXE) were prepared with three amino acid (AA) co-formers of increasing hydrophobicity: (i) L-lysine (LYS), (ii) L-valine (VAL) and (iii) L-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 (T_g = 91.2 °C). Hansen solubility parameters (Δδ_t < 4 MPa^1/2) 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 (), 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.

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.

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 in vitro, in vivo, and in silico approaches. The section also includes key toxicity mechanisms and challenges of smart nanomaterials in clinical translation.

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 Re-1 delivery for anxiety amelioration, memory improvement, and pathology reduction in an Alzheimer's Disease (AD) mouse model. FUS-BBBO was applied and Re-1 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 Re-1 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 Re-1 and FUS-BBBO for cognitive and minor pathological improvement in AD.