RSC Pharmaceutics最新文献

{"title":"Tryptophan intercalation in siRNA drives the formation of polymeric micelles with enhanced delivery efficiency†","authors":"Yuki Nakashima, Wenqian Yang, Pengwen Chen, Keita Masuda, Teahun Hong and Horacio Cabral","doi":"10.1039/D4PM00142G","DOIUrl":"https://doi.org/10.1039/D4PM00142G","url":null,"abstract":"<p >The construction of effective carrier systems is essential for delivering therapeutic small interfering RNA (siRNA). In this study, we present an innovative approach using tryptophan intercalation with siRNA to drive the formation of polymeric micelles. Through a facile yet robust method, the siRNA molecules are encapsulated within polymeric micelles formed by flexible poly(ethylene glycol)-poly(glycerol) (PEG-PG) block copolymers bearing biocompatible tryptophane units (PEG-PGTrp). Molecular dynamics (MD) simulations indicated the significance of the indole group, demonstrating its crucial role in fostering favorable interactions through π–π stacking. Moreover, the tryptophan moieties not only aid in the formation of stable micelles, but also contributed to intracellular trafficking and endosomal escape, thereby augmenting siRNA delivery. <em>In vitro</em> studies showed that the PEG-PGTrp-based micelles promoted intracellular delivery of siRNA, leading to enhanced gene knockdown.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 3","pages":" 513-523"},"PeriodicalIF":0.0,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/pm/d4pm00142g?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141980161","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":"Effect of amorphous chrysin loading in hydrophobically modified Pluronic F68 nanomicelles on its anticancer activity, stability and oral bioavailability","authors":"Harihar Narayan, Ashok Kumar Jangid, Jiten R. Sharma, Ankita Kishore, Alok Kumar Mahor, Umesh C. S. Yadav, Hitesh Kulhari and Prem Prakash Singh","doi":"10.1039/D4PM00074A","DOIUrl":"https://doi.org/10.1039/D4PM00074A","url":null,"abstract":"<p >Designing a potential polymer-based drug delivery carrier is of great significance for enhancing the anticancer effectiveness and oral delivery of hydrophobic phytodrugs. Chrysin (CRY) is a potential anticancer phytomolecule; however, its utilization for further applications is restricted due to its low aqueous solubility and poor bioavailability. Here, a biocompatible polymer, <em>i.e.</em> Pluronic F68 modified with stearic acid (F68–SA) was used for the fabrication of chrysin-loaded nanomicelles (CNMs). The fabricated CNMs comprised particles of 142.7 nm size with a spherical shape, amorphous nature, and a drug encapsulation efficiency of 37.06%. The incorporation of a hydrophobic segment into Pluronic F68 significantly enhanced the sustained drug release profile and stability. The CNMs effectively enhanced the anticancer effect against human lung A549 cancer cells, as confirmed by MTT, AO/EB, and cellular uptake assays. Moreover, the fabricated CNMs demonstrated a higher plasma chrysin concentration–time (<em>C</em><small>_max</small>) profile compared to a chrysin suspension. The AUC<small>_{0–<em>t</em>}</small> of the CNMs was also 5.6 times higher than that of the CRY suspension. These results indicate that the bioavailability of chrysin was significantly improved due to faster and enhanced absorption after administration as a nanomicelle formulation.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 4","pages":" 716-726"},"PeriodicalIF":0.0,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/pm/d4pm00074a?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142434719","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":"A pharmaco–technical investigation of oxaprozin and gaultheria oil nanoemulgel: a combination therapy","authors":"Talha, Ahsan Ali, Sradhanjali Mohapatra, Ayesha Siddiqui, Uzma Farooq, Athar Shamim, Pooja Jain, Mohammed Aslam, Ramsha Ansari, Mohd. Aamir Mirza and Zeenat Iqbal","doi":"10.1039/D4PM00112E","DOIUrl":"https://doi.org/10.1039/D4PM00112E","url":null,"abstract":"<p >Worldwide, osteoarthritis is a significant cause of pain, disability, and socioeconomic losses. The disorder's epidemiology is diverse and complicated. Chondrocyte viability and function are compromised by oxidative stress, mechanical stress, and inflammatory mediators. This reprogrammes the cells to undergo hypertrophic differentiation and early “senescence” and increases their susceptibility to pro-catabolic and pro-inflammatory mediators. Given the above discussed pathophysiology of osteoarthritis, it is anticipated that the combination of oxaprozin and gaultheria oil (utilized in traditional medicine for rheumatoid arthritis) will definitely help alleviate the multifactorial disease. The objective of the research was to develop and assess a nanoemulsion gel/nanoemulgel (NEG) by combining oxaprozin, a non-steroidal anti-inflammatory drug (NSAID), and gaultheria oil using Carbopol 974 as a gelling agent. The aqueous titration method was used to create the nanoemulsion by plotting a pseudo-ternary phase diagram, and <em>S</em><small>_mix</small> was used to draw the phase diagram. The formulation was optimized by employing the design of the experiment and incorporated into Carbopol 974 to formulate the NEG. Various properties of the developed formulation, such as the vesicular size, polydispersity index (PDI), zeta potential, morphology and thermodynamic stability, were tested. Furthermore, pH, homogeneity, spreadability, extrudability, texture, bioadhesion, stability, and skin irritation were assessed for the NEG. Additionally, <em>in vitro</em> and <em>ex vivo</em> tests were conducted for the assessment of the improved formulation. The result shows that the nanoemulsion has a vesicular size of 196.2 nm with good PDI and a zeta potential of −12.33 mV. Furthermore, the results show that the NEG had a biphasic release pattern with a percent cumulative drug release (%CDR) of 78.123 after 25 h. The optimized formulation was also found to be stable at 4 °C for up to 4 weeks. Furthermore, the NEG shows good drug penetration and sustained drug release pattern, which may facilitate the transport of oxaprozin and gaultheria oil through joint tissues, resulting in longer pain alleviation and decreased inflammation. In conclusion, the new formulation would be a good choice for topical medication delivery to improve the oil and oxaprozin combined therapeutic efficacy in the management of osteoarthritis.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 3","pages":" 484-497"},"PeriodicalIF":0.0,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/pm/d4pm00112e?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141980159","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":"Biopharmaceutical advancement of efonidipine hydrochloride ethanolate through amorphous solid dispersion of a Parteck SLC mesoporous silica polymer","authors":"Swati Bharati, Vinod Gaikwad and Bothiraja Chellampillai","doi":"10.1039/D4PM00113C","DOIUrl":"https://doi.org/10.1039/D4PM00113C","url":null,"abstract":"<p >Amorphous solid dispersion is the most efficient method for improving the solubility and release of poorly water-soluble crystalline drug molecules. Efonidipine hydrochloride ethanolate (EFE) shows solubility-limited oral bioavailability (BCS class II). The present investigation aimed to improve the solubility, bioavailability, and therapeutic efficacy of EFE using Parteck® SLC mesoporous silica based amorphous solid dispersion (EFESD). EFESD was prepared by employing a solvent evaporation method. An optimized composition (1 : 1 ratio) of solid dispersion was subjected to <em>in vitro</em>, <em>ex vivo</em>, and <em>in vivo</em> characterization. The solubility of EFE in the EFESD form was found to be 5- and 4-fold improved in distilled water and phosphate buffer (pH 6.8), respectively. An <em>ex vivo</em> permeability study performed using different parts of the Wistar rat small intestine (the duodenum, jejunum, and ileum) using a non-everted sac method showed 2-fold improvements in the permeability of EFE in EFESD. Moreover, <em>in vivo</em> pharmacokinetic and pharmacodynamic studies performed using male Wistar rats showed 1.41- and 2.10-fold increase in the area under the curve and <em>C</em><small>_max</small>, respectively, along with the improved anti-hypertensive activity of EFE in EFESD. Thus, amorphous solid dispersion with a novel applied Parteck® SLC 500 mesoporous silica formulation is an effective strategy to improve the biopharmaceutical properties of EFE.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 4","pages":" 765-774"},"PeriodicalIF":0.0,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/pm/d4pm00113c?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142434702","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":"Thermodynamic and kinetic analysis of the melting process of S-ketoprofen and lidocaine mixtures†","authors":"Kanji Hasegawa, Sara Ogawa, Hitoshi Chatani, Hikaru Kataoka, Tomohiro Tsuchida and Satoru Goto","doi":"10.1039/D4PM00039K","DOIUrl":"https://doi.org/10.1039/D4PM00039K","url":null,"abstract":"<p >Eutectic mixtures are often used in drug design and delivery. Herein, thermodynamic and kinetic analyses of the melting process of <em>S</em>-ketoprofen (KTP)/lidocaine (LDC) mixtures were performed by using differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR) measurements to trace the composition and melting process of KTP/LDC mixtures. In the binary solid–liquid phase diagram, a constant melting point of 294 K was observed, which is lower than the theoretical eutectic point of 304 K. It is believed that the hydrogen-bonding interactions between KTP and LDC caused a further decrease in the melting point. Melting at 304 K resulted from a eutectic reaction, whereas melting at 294 K was interpreted as the preliminary melting step. A kinetic analysis of the melting process was made possible by performing singular value decomposition (SVD) on a dataset of the FTIR spectra. The principal component vector indicating the magnitude of the contribution of the preliminary melting step reflects the time change in which the molten KTP signal increases after the molten LDC signal increases, which fits the sequential reaction equation. This confirms the preliminary melting stage at 294 K, as indicated by the binary solid–liquid phase diagram obtained by DSC. The activation energy was determined from the reaction rate constant, and a scenario for forming a eutectic mixture was proposed based on the mole fractions of KTP and LDC.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 3","pages":" 536-547"},"PeriodicalIF":0.0,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/pm/d4pm00039k?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141980163","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 the molecular structure of lipids in the design of artificial lipidated antifungal proteins†","authors":"Hendra Saputra, Muhammad Safaat, Kazuki Uchida, Pugoh Santoso, Rie Wakabayashi, Masahiro Goto, Toki Taira and Noriho Kamiya","doi":"10.1039/D3PM00087G","DOIUrl":"https://doi.org/10.1039/D3PM00087G","url":null,"abstract":"<p >Fungal infections have been a concern for decades, yet effective and approved antifungal agents are limited. We recently developed a potential method to enhance the antifungal activity of a small chitin-binding domain (LysM) from <em>Pteris ryukyuensis</em> chitinase A (PrChiA) by the site-specific introduction of a palmitoyl (C16) group catalyzed by microbial transglutaminase (MTG). Herein, we attempted the conjugation of a series of lipid–peptide substrates with LysM genetically fused with a C-terminal MTG-reactive Q-tag (LysM-Q) to yield LysM-lipid conjugates (LysM-lipids) with different lengths (LysM-C12, -C14, and -C16) and different numbers of alkyl chains [LysM-(C12)<small>₂</small>, -(C14)<small>₂</small>, and -(C16)<small>₂</small>]. The enzymatic conjugation proceeded smoothly for all LysM-lipids, except for LysM-(C16)<small>₂</small> because of the low aqueous dispersibility of the hydrophobic (C16)<small>₂</small> lipid–peptide substrate. The combination of amphotericin B (AmB) with LysM-C14 or LysM-C16 exhibited the highest antifungal performance against <em>Trichoderma viride</em> whereas alterations in the number of alkyl chains were not effective in enhancing the antifungal activity of the LysM-lipids. Fluorescent microscopic analysis showed that the fungal cell wall was stained with C14- and C16-modified LysM-muGFP fusion proteins when combined with AmB, suggesting a suitable lipid length to enhance the antifungal action. All LysM-lipids showed minimum cytotoxicity toward mammalian cells, suggesting that LysM-lipids could be a safe additive in the development of new antifungal formulations.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 2","pages":" 372-378"},"PeriodicalIF":0.0,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/pm/d3pm00087g?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141424754","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":"Microneedle-assisted transdermal delivery of carvedilol nanosuspension for the treatment of hypertension","authors":"Anushri Deshpande, Vidhi Mer, Darshana Patel and Hetal Thakkar","doi":"10.1039/D4PM00038B","DOIUrl":"https://doi.org/10.1039/D4PM00038B","url":null,"abstract":"<p >Carvedilol nanosuspension loaded microneedles patch was formulated and characterized by particle size,  zeta potential, solubility, Transmission Electron Microscopy, X-Ray Diffraction, in-vitro release and <em>in-vivo</em> pharmacokinetic studies A nanosuspension-loaded microneedle patch was successfully prepared and characterized by optical microscopy, scanning electron microscopy, axial fracture force, <em>in vitro</em> dissolution study, % drug content, <em>in vitro</em> drug-release study, <em>ex vivo</em> studies, an <em>in vivo</em> study, and stability studies. The particle size, PDI, and zeta potential of the carvedilol nanosuspension were found to be 179.6 ± 1.15 nm, 0.163 ± 0.01, and −14.2 ± 0.55 mV, respectively. There was a 9.21-fold increase in the saturation solubility of the carvedilol nanosuspension. Nanosuspension-loaded microneedles contained 98.78 ± 0.12% carvedilol. The relative bioavailability of the carvedilol from the microneedle patch was found to be 2.82-fold higher compared to the marketed formulation. The drug release from the microneedles followed zero-order kinetics, which is desirable in the case of transdermal delivery. The stability study indicated that the prepared formulation was stable under the storage conditions used. Thus, the developed transdermal microneedle patch containing the carvedilol nanosuspension seems to be a promising approach to foster greater patient compliance for the management of hypertension.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 3","pages":" 472-483"},"PeriodicalIF":0.0,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/pm/d4pm00038b?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141980158","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":"Lysozyme activated co-delivery of latanoprost–timolol from mucoadhesive chitosan nanocomposite to manage glaucoma†","authors":"B. N. Kumara, R. Shambhu, Yoon-Bo Shim and K. Sudhakara Prasad","doi":"10.1039/D4PM00031E","DOIUrl":"https://doi.org/10.1039/D4PM00031E","url":null,"abstract":"<p >Glaucoma is a leading cause of irreversible blindness, and controlling intraocular pressure is imperative for good clinical outcomes. It is important to use natural stimuli to trigger the release of the drug when it is linked to a nanoparticle/nanocomposite, particularly in ophthalmic applications to maintain sustained release. Herein the preparation and investigation of biocompatible, mucoadhesive dual drug-loaded chitosan (CS)–graphene quantum dot (GQD) nanocomposites are reported. Drug release from the nanocomposite was controlled by the presence of a natural lacrimal fluid enzyme, lysozyme (Lyz). Lyz is efficient at cleaving the β-1,4 glycosidic linkages of CS, thereby releasing the drug of interest. A biocompatible, fluorescent nanomaterial <em>i.e.</em>, GQDs, was employed to track drug loading by using simple photoluminescent spectral studies. The optimized nanocomposite encapsulation efficiencies (EEs) were 94.51% and 74.08% for latanoprost (LP) and timolol (TM) and delivered 32.68% and 66.61% of drugs, respectively, in 72 h. Dual drug delivery through the cleavage of β-1,4 glycosidic linkages of CS in the presence of Lyz was confirmed through <small>¹</small>H-NMR and FE-SEM studies. An increase in the particle size from 490 nm to 1584 nm in the presence of mucin supports the mucoadhesiveness of the nanocomposite. The <em>in vitro</em> cytocompatibility and live/dead staining assays against human corneal epithelial (HCE) cells showed ≥80% cell viability. <em>Ex vivo</em> tests proved that the nanocomposite was non-irritant, and histopathological studies showed normal growth of blood vessels. Molecular docking studies showed the hydrogen bonding and electrostatic interactions between the drug and CS. Hence the developed nanocomposite could be used as an ocular suspension or nanocomposite for further preclinical studies on glaucoma management.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 3","pages":" 548-569"},"PeriodicalIF":0.0,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/pm/d4pm00031e?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141980177","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":"Acid- and base-resistant antimicrobial hydrogels based on polyoxometalates and chitosan†","authors":"Callum McWilliams, Isabel Franco-Castillo, Andrés Seral Ascaso, Sonia García-Embid, Mariella Malefioudaki, Johann G. Meier, Rafael Martín-Rapún and Scott G. Mitchell","doi":"10.1039/D4PM00062E","DOIUrl":"https://doi.org/10.1039/D4PM00062E","url":null,"abstract":"<p >Invasive fungal infections kill more than 1.7 million and affect over a billion people each year; however, their devastating impact on human health is not widely appreciated and frequently neglected by public health authorities. In 2022, the WHO highlighted the urgent need for efficient diagnostic tests as well as safe and effective new compounds, drugs, and vaccines. Our hypothesis was that the naturally occurring polymer chitosan (CS) could be combined with molecular polyoxometalates (POMs) to produce POM@CS hybrid materials to promote broad-spectrum activity and habilitate synergic effects, which will ultimately help to prevent the appearance of resistances. Here we report the synthesis, characterisation, and antimicrobial activity of POM@CS hydrogels. Spectroscopic (FT-IR &amp; EDS) and electron microscopy (SEM &amp; TEM) techniques revealed the structural composition and morphology of the hybrid materials, whilst dynamic mechanical analysis demonstrated that the mechanical properties of the hydrogels were stable between pH 2 and 10 and were highly resistant to acidic conditions. The POM@CS hydrogels were active against Gram-positive <em>Bacillus subtilis</em> and Gram-negative <em>Escherichia coli</em> bacteria, and proved to completely reduce fungal growth of <em>Aspergillus niger</em> and <em>Cladosporium cladosporioides</em>. Furthermore, the antimicrobial activity of the hydrogels could be enhanced through the inclusion of naturally occurring antimicrobial agents such as eugenol and cinnamaldehyde. Altogether, the development of such surface-active antimicrobial hydrogels pave the way to functional materials that can prevent biofilm formation in health and environmental applications and contribute to reducing the spread of antimicrobial resistance.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 4","pages":" 755-764"},"PeriodicalIF":0.0,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/pm/d4pm00062e?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142434701","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":"Doxorubicin-Polysorbate 80 conjugates: targeting effective and sustained delivery to the brain†","authors":"S. Ram Prasad, Sruthi Sudheendran Leena, Ani Deepthi, A. N. Resmi, Ramapurath S. Jayasree, K. S. Sandhya and A. Jayakrishnan","doi":"10.1039/D4PM00053F","DOIUrl":"https://doi.org/10.1039/D4PM00053F","url":null,"abstract":"<p >Targeting therapeutic agents to the brain to treat central nervous system (CNS) diseases is a major challenge due to the blood–brain barrier (BBB). In this study, an attempt was made to deliver a model drug such as doxorubicin (DOX), to the brain in a mouse model through DOX-Polysorbate 80 (DOX-PS80) conjugates. DOX was successfully conjugated with the non-ionic surfactant Polysorbate 80 (PS80) by carbamate linkage and the conjugate was characterized by different spectroscopic techniques, such as FTIR, UV-Visible and NMR. The DOX conjugation efficacy was found to be 43.69 ± 4.72%. The <em>in vitro</em> cumulative release of DOX from the conjugates was found to be 4.9 ± 0.8% in PBS of pH 7.3 and 3.9 ± 0.6% in simulated cerebrospinal fluid (CSF) of pH 7.3 at the end of 10 days. An <em>in vitro</em> BBB permeability assay was carried out using bEnd.3 cells and DOX-PS80 conjugate showed a 3-fold increase in BBB permeability compared with controls. <em>In vitro</em> cytotoxicity assay using U251 human glioblastoma cells showed an IC<small>₅₀</small> value of 38.10 μg mL<small>⁻¹</small> for DOX-PS80. Cell uptake studies revealed that DOX-PS80 was effectively taken up (90%) by the bEnd.3 and U251 cells and localized in cytoplasm at the end of 24 h. Pharmacokinetic parameters for DOX-PS80 were evaluated using <em>in silico</em> studies. Tumor spheroid assay and <em>in vivo</em> experiments in Swiss albino mouse demonstrated the possibility of DOX-PS80 conjugate crossing the BBB and delivering the drug molecules to the target site for treating CNS disorders.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 3","pages":" 412-429"},"PeriodicalIF":0.0,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/pm/d4pm00053f?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141980149","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}