RSC Pharmaceutics最新文献

One of the most interesting applications of artificial intelligence is in the design of drug delivery systems. Smart drug delivery systems can transfer drugs to specific tissues and cells, enhancing therapeutic effects while reducing undesirable side effects. Attention is focused on the main concepts and techniques of AI such as machine learning, deep learning, and genetic algorithms. In addition to this, genetic algorithms can be used for the selection of the best numerical models, which are able to predict biological processes or optimize the activity of new drugs. Besides the powerful impact of AI on drug design, its combination with new biotechnologies for personalized medicine, sometimes called theragnostics, brings novel diagnostic tools together with targeted therapy, which could ensure quality and effectiveness during clinical research on new drugs. Artificial intelligence (AI) techniques are finding their application in almost all disciplines, with particular success in healthcare. AI-based algorithms can solve complex problems related to diagnosis, prediction, control, and prevention of diseases that are beyond the scope of human abilities. At the same time, the Internet of Things (IoT) revolution has added value to the healthcare sector. The resulting combination of IoT and AI platforms presents a promising fusion to provide healthcare delivery innovations like digital drug delivery, online healthcare consultancy platforms, and virtual healthcare assistants. Personalized medicine is well-suited, regardless of potential disadvantages, to creating drug delivery systems that can respond to the exact needs and other special requirements of patients. The development of smart drug delivery systems is a potential response to the unimodal properties of drugs and the discordance between patient requirements and patient outcomes achieved by currently prescribed medications. The potential and actual positive economic and health-related impacts of advanced drug delivery technologies have created strong demand for new advanced delivery forms.

PARK7 mRNA encodes the DJ-1 protein, which functions as a protective agent against oxidative stress and cell damage within brain cells. Mutations in the mRNA can lead to reduced production of DJ-1 and initiate brain diseases such as Parkinson's disease. Transport of appropriate mRNA to damaged brain cells may provide a suitable treatment. Mesoporous silica nanoparticles (MSNPs), particularly pore-expanded and dye-labeled varieties, are regarded as potential carriers for large therapeutic agents such as mRNA. This study explored the influence of alterations in reaction conditions on the structural characteristics of MSNPs to produce nanoparticles with favorable characteristics for delivering large therapeutic agents to target sites. One-stage and two-stage procedures were compared for the introduction of 3-aminopropyltriethoxysilane (APTES) and an APTES−dye adduct, in conjunction with two different surfactants, cetyltrimethylammonium bromide (CTAB) and cetyltrimethylammonium chloride (CTAC). Analysis of the MSNPs shows that the two-stage method using CTAB as a surfactant produced amine-functionalized, dye-labelled particles with smaller overall size and better uniformity than the one-stage approach. However, due to their small pore size (<10 nm), these particles were unable to encapsulate the PARK7 mRNA (926 nucleotides). The one-stage method via CTAC produced MSNPs with a large pore size (150 nm), broad pore distribution (10–20 nm), and high aggregation, limiting their suitability for brain-targeted gene delivery. In comparison, the two-stage method using CTAC yielded well-ordered MSNPs with an optimal size (80 nm) and pore diameters (15–20 nm), enabling effective encapsulation of the large PARK7 mRNA and offering strong potential for future brain gene therapy studies.

Surfactant protein-A (SP-A) is an endogenous and essential lung surfactant-specific protein that is integral to pulmonary immunity, including inhibition of asthma exacerbations. This study aims to comprehensively characterize two peptides (10-AA and 20-AA) of SP-A which confer activity similar to the full-length oligomeric SP-A protein. Spectroscopic and chromatographic analyses revealed that the phosphate (PS) and acetate (AC) salts exhibited distinct solubility and log P partitioning behavior, impacting their physicochemical properties. MD simulations and circular dichroism showed that SP-A 10-AA initially adopts an α-helical structure but loses helicity over time, while SP-A 20-AA remains disordered. Differential scanning calorimetry confirmed variations in thermal stability between salt forms and zeta potential measurements showed that PS salts had a more negative surface charge, potentially influencing membrane interactions. In vitro studies showed high cell viability (>90%) and stable TEER values at the air–liquid interface, confirming biocompatibility and potential epithelial permeability. These findings provide crucial insights into the structural and functional properties of SP-A peptides, supporting their potential as therapeutic agents for pulmonary diseases.

Wound healing is a multifaceted and dynamic biological process, which traditional wound dressings often fail to adequately support, leading to prolonged healing times. It would be highly beneficial to develop wound dressings with the ability to support biological processes such as cell proliferation and angiogenesis and deliver the active agents required to restore intracellular activities to promote wound healing. The current work aimed at developing a polyelectrolyte complex of chitosan (CH) and an anionic polymer, condensed with calcium phosphate (CaP) powder to attain antibacterial and angiogenic potential, cell proliferation, appropriate swelling index, and enhanced wound healing. Polyelectrolyte complexes (PECs) were formulated using chitosan (CH), as a cationic polymer and pectin (PE), sodium alginate (SA), and carrageenan (CA), respectively, as an anionic polymer through a lyophilization process. PEC formation was confirmed by FTIR, XRD, and DSC by observing the changes in their vibrational frequencies, structures, and thermal properties. SEM revealed the porous structure of the scaffolds. From the prepared PEC scaffolds, chitosan–carrageenan (CH-CA) was selected for further studies based on the swelling index, porosity, and degradation studies. Following the production of CaP powder using a microwave-assisted synthesis method, the powder was characterized by FTIR, SEM, XRD, and energy dispersive X-ray (EDX) techniques before being loaded onto CH-CA scaffolds. The results demonstrated approximately 60.75% release of calcium ions (Ca⁺⁺) from the CH-CA scaffolds in PBS, pH 5.5, as analysed by atomic absorption spectroscopy (AAS) over 24 h. The scaffolds demonstrated a higher swelling index and exhibited antimicrobial activity against E. coli and S. aureus. The scaffolds were found to be hemocompatible and demonstrated angiogenic potential, evidenced by stimulating new blood vessel development in a chick yolk sac membrane assay. Cell proliferation studies demonstrated the cytocompatibility of the scaffolds, and improvement in the cell density of the L929 mouse fibroblast cell line was observed in a live/dead assay. In conclusion, the calcium-loaded CH-CA scaffolds demonstrated antimicrobial properties, increased angiogenesis, blood compatibility, and cell proliferation, indicating their potential as an appropriate wound dressing material.

Supplying vitamin D supplements to all older adults is beneficial and cost-effective. However, operationalising this supply to residents in long-term care is problematic. This study aimed to understand the challenges of vitamin D supplement provision by auditing the extent of supplementation, measuring the quality of the supplements and investigating the attitudes towards supplement provision in UK care homes. This case study investigated the supply of vitamin D supplement formulations in four UK care homes and analysed the vitamin D content of nine formulation types. It employed semi-structured interviews with care home stakeholders to understand attitudes toward vitamin D supply. Across the nine analysed products, there was >50% variability in their quality (75–137% of the label), but 44% of supplements were of medicinal grade. One tablet from a food-grade product contained 167% vitamin D, and one medicinal-grade tablet only contained 70% vitamin D. Interviews with care home staff highlighted four challenges to providing supplements: the perceived responsibility of healthcare professionals to supplement, difficulties obtaining prescription medications, the absence of national/local strategies, and the financial burden. This study demonstrated sub-optimal vitamin D supplement supply to care home residents, with staff unclear about who was responsible for choosing the correct type of vitamin D supplement, who paid for it, and who was to supply it. This study suggests a new approach to delivering vitamin D supplements to older adults is needed.

Poor response and associated side effects of available drugs in clinics have limited successful asthma management. Traditionally, bromelain has been found effective in asthma management; however, its use is limited by the need for high oral doses and poor bioavailability. Therefore, the present investigation was tailored to prepare bromelain-loaded lipid–polymer hybrid nanoparticles (Br-LPHNs) to enhance the oral bioavailability and therapeutic efficacy of bromelain in the management of allergic asthma. Br-LPHNs, consisting of a lipid core encapsulated in a biomimetic polymethylmethacrylate coating, were prepared utilizing the double emulsion solvent evaporation method. The drug release behavior, mucolytic potential and stability of the optimized formulation were evaluated. Pharmacokinetic and pharmacodynamic studies were executed in an allergen-induced asthma model. The optimized Br-LPHNs exhibited a nanosize (190.91 ± 29.48 nm) and high entrapment efficiency (89.94 ± 3.98%), along with gastro-resistant and sustained drug release behavior for up to 24 h. Using LPHNs as a carrier improved shelf life (∼6.99-fold) and bioavailability (6.89-fold) compared to pure bromelain. The optimized formulation significantly suppressed bronchial hyperresponsiveness, delayed the onset of bronchospasm and reduced its severity. Moreover, oxidative and immunological markers were significantly (p < 0.05) reduced, accompanied by the restoration of antioxidant enzyme levels to normal. Histopathological investigations also confirmed reduced tissue injury. Thus, the development of Br-LPHNs not only ensured in vitro and in vivo stability of bromelain but also offered a promising approach for asthma management.

A liver surface application (LSA) was developed to reduce the side effects of chemotherapy in liver cancer. The effects of molecular weight (MW) and lipophilicity (log PC) on the absorption of hydrophilic and lipophilic compounds from the rat liver surface were examined. However, how these two factors simultaneously affect compound absorption remains unclear. The combined effects of MW and log PC on the absorption of these compounds in rats and mice were investigated. The compounds were administered to the liver surface using a cylindrical diffusion cell, and in vitro release experiments were conducted using a dialysis membrane to explore the relationship between release and absorption. The results indicate that log (PC/MW^0.5) has a significant linear correlation with log P_{app, absorption} (P_app, apparent permeability coefficient). Similarly, a significant correlation was observed between log (PC × P_{app, release}) and log P_{app, absorption}. These two relationships observed in rats were used to predict compound absorption in mice, and the predicted values closely matched the experimental data. This implies that both combinations of MW and in vitro release with log PC can explain compound absorption from the liver surface. This study provided important information for understanding the absorption characteristics of LSA.

Liver fibrosis is a progressive and fatal condition characterized by stiffness and scarring of the liver due to excessive buildup of extracellular matrix (ECM) proteins. If left untreated, it can progress to liver cirrhosis and hepatocellular carcinoma (HCC)–one of the fastest-rising causes of cancer mortality in the United States. Despite the increased prevalence of liver fibrosis due to infections, exposure to toxins, and unhealthy lifestyles, there are no effective treatments available. Recent advances in nanomedicine can lead to more targeted and effective strategies for treating liver diseases than existing treatments. In particular, the use of biomimetic nanoparticles (NPs) such as liposomes and cell-membrane-coated NPs is of interest. NPs functionalized with cell membranes mimic the properties of the source cell used and provide inherent immune evasion ability, homologous adhesion, and prolonged circulation. This review explores the types of biomimetic coatings, different cargoes delivered through biomimetic NPs for various treatment modalities, and the type of core NPs used for targeting liver fibrosis and HCC.

Hydroxyapatite nanoparticles (HAP NPs) with distinct morphologies were synthesized by the wet precipitation method by varying pH, and their shape was confirmed by scanning electron microscopy as spherical (pH 12), rod-like (pH 9), and needle-like (pH 8). The particle sizes of HAP NPs were 96.86 ± 1.48 nm for needle-shaped, 118 ± 4.32 nm for rod-shaped, and 94.43 ± 1.02 nm for spherical-shaped particles. XRD analysis showed clear and distinct peaks indicating crystalline nature, while FTIR confirmed the characteristic features of hydroxyapatite. The negative zeta potential of the HAP NPs was attributed to the presence of surface phosphate ions. The influence of HAP NP shape and size on intracellular uptake was evaluated in the MG-63 osteosarcoma cell line by Confocal Laser Scanning Microscopy (CLSM). CLSM results demonstrated that rod-shaped HAP NPs predominantly localized within the lysosome and nucleus, while spherical HAP NPs accumulated at the cell membrane. The MTT, clonogenic survival, cell scratch and transwell migration assays revealed that rod-shaped HAP NPs exhibited superior anticancer activity compared to their needle- and spherical-shaped counterparts and completely suppressed the clonogenic survival of MG-63 cells. Our findings confirm that the shape of HAP NPs is a critical factor influencing their intracellular uptake and anticancer activity.

A database of 1242 experimentally synthesized COFs has been studied to understand their potential as drug carriers by employing molecular simulations and machine learning models to analyze the adsorption abilities and predict the capacity of loading the anticancer drug, 5-fluorouracil. Our findings indicate that different organic linkers, structural features, binding sites, topologies, etc. of COFs play an important role in determining the maximum loading capacity and release parameters of 5-FU. The implementation of molecular simulations-based machine learning methods for drug adsorption studies in COFs is rare in the literature. Once the model was validated, we studied the maximum loading capacity of 5-FU in a series of COFs, 102–108 and 112, from the COF database, as these exhibited a gradual trend in textural properties, aiming to understand this trend and the correlation between their structure and loading capacity. Then, we proceeded to study the adsorption process in detail in 4 of the COFs: three 2D COFs—COF-206, i.e., D_CuPc–A_NDI-COF; COF-362, i.e., PI-COF-3; and COF-398, i.e., Py-DBA-COF-1—and one 3D COF—COF-363, i.e., PI-COF-4. Radial distribution function and adsorption energy analyses revealed some important interactions and thermodynamic parameters leading to strong binding and slow release of 5-FU. The adsorption energy values in the top-performing COFs fall within the range of −8.43 to −42.25 × 10³ kJ mol⁻¹. The correlation of ML input parameters in terms of various chemical and structural descriptors with the maximum loading capacity is discussed. From the molecular simulations, COF-362 is the best-performing COF in terms of loading capacity and adsorption energy values. The ML models, i.e., random forest, decision tree and three deep neural networks, were trained on 80% of the total data, while the remaining 20% of the data was used to test the models. DNN model-3 was chosen as the final model for further analysis based on R² = 0.87, RMSE = 189.81, and MAE = 100.87. SHapley Additive exPlanations (SHAP) analysis and the feature importance chart indicated that among the structural descriptors, S_acc, LCD, and V_f, and among the chemical descriptors, C, H, and N, had the most positive impact on the output predictions of the model. Finally, a graphical user interface based on the best-performing ML model was created to predict the 5-FU loading capacity of COFs. This will save users time without the need to run the code or perform various tedious drug-loading experiments.