RSC Pharmaceutics最新文献

{"title":"Dual-purpose resveratrol-quantum dots loaded albumin nanoparticles†","authors":"Deepankar Yadav, Priyanka Chaudhary, Priya Singh, Monu Gupta and Shubhini A. Saraf","doi":"10.1039/D4PM00100A","DOIUrl":"https://doi.org/10.1039/D4PM00100A","url":null,"abstract":"<p >Incorporating therapeutic and imaging capabilities into core–shell structured nanoparticles (NPs) has shown promising results in cancer treatment. This study aims to develop paddy husk carbon quantum dots (QDs) encapsulated in bovine serum albumin (BSA) nanoparticles with resveratrol (RSV) to enhance antioxidant activity and bioimaging potential. Carbon QDs, approximately 10 nm in size, were synthesized and characterized by UV-visible spectroscopy, photoluminescence spectroscopy, TEM, and FTIR. The optimized formulation was achieved using a full-factorial design, resulting in a combination of BSA with concentration of 219.004 mg, RSV with concentration of 8.271 mg, and 4 mL of ethanol. The nanoparticles exhibited a particle size of 125.6 nm, a zeta potential of −0.570 mV, 63.06% entrapment efficiency, and 7.173 mg drug content. <em>In vitro</em> assays showed that the nanoparticles enhanced RSV release under mildly acidic conditions, demonstrating efficacy as intracellular drug carriers. Cytotoxicity assays against MDA-MB-231 cells revealed dose- and time-dependent cytotoxicity, with 72% cell viability for the optimized formulation at the highest concentration tested. Antioxidant activity was 96% for the optimized formulation, compared to 35–45% for QDs and 80–85% for RSV alone, as measured by DPPH and H<small>₂</small>O<small>₂</small> assays. Confocal microscopy confirmed the superior imaging capability of the QDs. These findings indicate that QD- and resveratrol-loaded albumin nanoparticles (ANPs) have the potential to serve as effective cancer therapeutic agents and as biological imaging probes.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 4","pages":" 806-819"},"PeriodicalIF":0.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/pm/d4pm00100a?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142434706","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 brief overview of quality by design approach for developing pharmaceutical liposomes as nano-sized parenteral drug delivery systems","authors":"Prachi Atre and Syed A. A. Rizvi","doi":"10.1039/D4PM00201F","DOIUrl":"https://doi.org/10.1039/D4PM00201F","url":null,"abstract":"<p >Liposomes are sophisticated drug delivery vehicles that have significantly broadened the range of therapeutic agents that can be selectively delivered along with controlled release. Liposomes are small vesicles (size optimizable) composed of a lipid bilayer that encapsulates hydrophilic as well as hydrophobic drugs. This advancement has led to the creation of liposomal nano-formulations for drugs with very poor water solubility and cell membrane permeability, resulting in improved therapeutic efficacy and reduced side effects. Liposomal formulations can also be engineered with ligands or antibodies to target specific cells or tissues, ensuring site-specific drug delivery and minimizing off-target side effects. These targeted liposomal formulations have shown promising potential in treating various diseases, such as cancer, infectious diseases, and inflammatory disorders. With continuous advancements in liposomal technology, researchers are exploring new ways to further optimize the liposomal formulations for enhanced drug stability, bioavailability, and targeted delivery to specific cells or tissues. The Quality by Design (QbD) approach is a systematic and scientific method for designing and developing pharmaceutical products, ensuring quality and consistency throughout the product lifecycle. Applied to the development of pharmaceutical liposomes, QbD facilitates the optimization of liposome formulations for targeted drug delivery, improved stability, and enhanced therapeutic outcomes. The creation of novel liposomal formulations with superior drug stability, bioavailability, and targeting capabilities will undoubtedly play a crucial role in shaping the future of medicine and improving patient care. This brief review provides an overview of the development of liposomes as nanocarrier systems for parenteral drug delivery, covering aspects such as quality manufacturing attributes, structure, preparation methods, characterization, clinical applications, and regulatory considerations.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 4","pages":" 675-688"},"PeriodicalIF":0.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/pm/d4pm00201f?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142434716","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":"Antimicrobial coatings from gramicidin D nanoparticles and polymers","authors":"Livia Cestaro de Souza Camargo, Bianca Reche Bazan, Rodrigo Tadeu Ribeiro, Giovanna Maruyama Quinto, Andrea Caroline Bazzan Muniz and Ana Maria Carmona-Ribeiro","doi":"10.1039/D4PM00124A","DOIUrl":"https://doi.org/10.1039/D4PM00124A","url":null,"abstract":"<p >The microbicidal activity of gramicidin D molecules (Gr) assembled as nanoparticles (NPs) against <em>Staphylococcus aureus</em> was found to be superior to that of other Gr formulations in bilayers. In combination with the antimicrobial polymer poly(diallyl dimethyl ammonium chloride) (PDDA), water dispersions and coatings on glass exhibited a remarkably broadened spectrum of activity, achieving complete killing of Gram-negative bacteria, Gram-positive bacteria and fungi at reduced Gr and PDDA doses. In this work, combinations of Gr NPs and polymers were cast on glass (hydrophilic) or polyethylene (hydrophobic) surfaces, modeling common surfaces on biomedical materials, to evaluate the effect of polymer positive charge on the antimicrobial activity. Decreasing positive charges of three different polymers, namely PDDA, chitosan (CH) and polyacrylamide (PA), reduced or abolished microbicidal activity both in the presence and absence of Gr NPs. At 4.7 μg Gr and 25 μg polymer, microbicidal activity increased from PA to CH to PDDA at pH 6.3. The results suggested that the Gr/polymer antimicrobial coatings can be used on both hydrophobic and hydrophilic biomedical materials, effectively imparting them with efficient defense against a broad spectrum of microbes.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 5","pages":" 1033-1041"},"PeriodicalIF":0.0,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/pm/d4pm00124a?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798215","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":"Evaluation of drug release from polymeric nanoparticles in simulated saliva and gastric media by asymmetric flow field–flow fractionation (AF4)†","authors":"Haoran Wu, Alaia Homawoo, Saba Shariati, Carlos E. Astete, Debora F. Rodrigues, Cristina M. Sabliov, Elham H. Fini and Stacey M. Louie","doi":"10.1039/D4PM00175C","DOIUrl":"https://doi.org/10.1039/D4PM00175C","url":null,"abstract":"<p >Nanocarriers for oral drug delivery will encounter various biochemical environments throughout the digestive tract, which could induce different drug release behaviors. Conventional drug release assays can provide total drug release rates but have limited capability to identify drug release mechanisms in complex samples. The objective of this study is to compare the rates and mechanisms for release of an antibiotic, enrofloxacin, from poly(lactic-<em>co</em>-glycolic acid) (PLGA) nanoparticles in simulated saliva and simulated gastric fluid (SGF) by combining drug release profiling using asymmetric flow field–flow fractionation (AF4) with physical release models and density functional theory (DFT) analyses. At 30 °C, similar release profiles were observed in media with near-neutral pH, represented by saliva and phosphate buffered saline (PBS) as a comparative medium, whereas antibiotic release was accelerated in SGF. However, negligible drug release was observed in SGF at room temperature (below the glass transition temperature of the nanoparticles). Enzymatic proteins in the media did not significantly influence the release rates. The advanced AF4 analyses of the drug distribution and release profiles affirmed negligible drug–protein interactions in the media and provided evidence that accelerated release in SGF was attributed to enhanced radial diffusion rates of entrapped drug through the nanoparticles, rather than particle erosion or shrinking. DFT modeling further demonstrated that changes in the charge state of the enrofloxacin and carboxylated PLGA result in diminished drug–polymer interactions upon SGF intrusion into the nanoparticles. Altogether, this study demonstrates the benefits of integrated experimental and modeling analyses to understand drug release mechanisms.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 5","pages":" 994-1007"},"PeriodicalIF":0.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/pm/d4pm00175c?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798078","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":"Correction: Pharmaceutical salts of azole anti-fungal drugs: physicochemical behaviour and activity studies","authors":"Hafsa Qadri, Asif A. Malik, Aadil A. Ahangar, Manzoor Ahmad Mir, Aijaz A. Dar and Abdul Haseeb Shah","doi":"10.1039/D4PM90015D","DOIUrl":"https://doi.org/10.1039/D4PM90015D","url":null,"abstract":"<p >Correction for ‘Pharmaceutical salts of azole anti-fungal drugs: physicochemical behaviour and activity studies’ by Hafsa Qadri <em>et al.</em>, <em>RSC Pharm.</em>, 2024, https://doi.org/10.1039/d4pm00003j.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 4","pages":" 854-854"},"PeriodicalIF":0.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/pm/d4pm90015d?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142434728","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":"Programmable protein delivery from microgel/hydrogel composites (MHCs) via discrete combinations of multi-state protein-loaded unit ingredients†","authors":"Longfei Chen and Saif A. Khan","doi":"10.1039/D4PM00080C","DOIUrl":"https://doi.org/10.1039/D4PM00080C","url":null,"abstract":"<p >Therapeutic proteins have drawn increasing attention in the development of advanced drugs and biomedical devices, yet there are outstanding challenges for the delivery of multiple-protein therapies with customized release profiles. Hydrogel-based drug delivery systems (DDS) have been widely investigated, primarily <em>via</em> highly specific chemical modification routes, for programmable topical, injectable, and depot-based protein delivery. In this paper, we propose a microgel/hydrogel composite (MHC) DDS for tunable and programmable multi-protein delivery, which leverages different <em>physical states</em> of proteins (freely dissolved or coacervated) and completely avoids bespoke chemical modifications on the hydrogels. We load model proteins in distinct physical states into dextran-based hydrogel microparticles (microgels) fabricated using microfluidics, after which simple discrete combinations of these microgel ‘unit ingredients’ are packaged into poly(ethylene glycol) hydrogel matrices to formulate the MHC DDS. With discrete combinations of unit ingredients, we demonstrate how these MHC DDSs can achieve both <em>tunable</em> release for a single low-molecular-weight model protein (and ideally, highly similar proteins) and a counterintuitive <em>rate-reversed</em> release of two model proteins that are vastly different in size. Moreover, we show that these MHCs follow Korsmeyer-Peppas kinetic behavior as a function of the discrete combinations packaged, thus highlighting the quantitative tunability of release behaviors. We envision the use of these MHC DDSs as topically applied wound dressings or implantable protein-releasing depots that allow scheduled and programmable multi-protein delivery in biomedical and clinical applications.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 4","pages":" 689-704"},"PeriodicalIF":0.0,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/pm/d4pm00080c?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142434717","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":"Cancer immunotherapy boosted by layered double hydroxide nanoparticles","authors":"Xiaochun Deng, Gaoming Li, Mingwu Shen and Xiangyang Shi","doi":"10.1039/D4PM00179F","DOIUrl":"https://doi.org/10.1039/D4PM00179F","url":null,"abstract":"<p >The development of innovative nanoplatforms for cancer immunotherapy has garnered considerable attention in biomedical research. Layered double hydroxide (LDH) is a two-dimensional inorganic nanomaterial consisting of positively charged brucite-like cationic layers and negatively charged anions intercalated in the interlayer space. LDH-based nanoplatforms have been emerging as promising candidates for enhancing the efficacy of cancer immunotherapy. This review highlights the latest advancements in the application of LDH in cancer immunotherapy. The unique physicochemical properties of LDH, such as a high surface area, tunable porosity, and facile surface modification, entail it to be a versatile platform to deliver antigens, drugs, and other therapeutic agents. In addition, LDH's inherent biocompatibility and biodegradability contribute to its suitability for <em>in vivo</em> applications. Moreover, the nanoplatform formed by the integration of self-adjuvant LDH with tumor antigen and immunomodulatory components has shown promising results in enhancing antigen presentation, promoting immune cell activation and regulating the immune suppressive tumor microenvironment. In this review, we discuss the application of LDH as a carrier-supported immune modulator in immunotherapy and the application of LDH as an adjuvant to construct tumor vaccines. Finally, future research challenges of LDH in immunotherapy are briefly discussed. Conclusively, the versatility and adaptability of LDH-based nanoplatforms make them promising candidates for the next generation of cancer immunotherapeutics.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 4","pages":" 608-621"},"PeriodicalIF":0.0,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/pm/d4pm00179f?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142434713","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":"Nose to brain targeting of the donepezil nanostructured lipid carrier in situ gel: formulation, in vitro, ex vivo, in vivo pharmacokinetic and pharmacodynamic characterization†","authors":"Devika Sonawane and Varsha Pokharkar","doi":"10.1039/D4PM00174E","DOIUrl":"https://doi.org/10.1039/D4PM00174E","url":null,"abstract":"<p >Donepezil (DPZ) is a reversible, noncompetitive inhibitor of acetylcholinesterase commonly prescribed against Alzheimer's disease (AD). Its dose-dependent side effects limit its therapeutic benefits. The current study endeavors to design an <em>in situ</em> gel for intranasal delivery of a DPZ nanostructured lipid carrier (DPZ-NLC) to boost pharmacokinetic and pharmacodynamic outcomes. The Box–Behnken design was employed to optimize the NLCs that were produced utilizing a melt emulsification high-pressure homogenization process. Afterward, NLCs were embedded in an <em>in situ</em> gel based on Lutrol F127 and analyzed further. The effects of formulation pharmacodynamics were evaluated in a Wistar rat model with trimethyl tin (TMT) induced neurodegeneration. The batch of the optimized DPZ <em>in situ</em> gel had a spherical shape, with a mean particle size of 112.5 ± 2.44 nm. It showed a high drug entrapment of 98.7 ± 4.01% and an <em>in vitro</em> drug release of 89.51 ± 2.94%. With a <em>C</em><small>_max</small> value of 193.41 ± 26.4 ng mL<small>⁻¹</small> and a <em>T</em><small>_max</small> value of 2 hours, the drug's significant therapeutic concentration in the CNS following intranasal (IN) administration was demonstrated by <em>in vivo</em> single-dose pharmacokinetic investigation. The Drug Targeting Efficiency (DTE) of 213.123% and the Drug Targeting Potential (DTP) of 66.27% were greater for the constructed DPZ <em>in situ</em> gel, indicating superior brain targeting efficiency through NLCs. The outcomes showed that as compared to the neurodegeneration control group, the DPZ <em>in situ</em> gel treatment group dramatically reduced the escape latency and path length. The DPZ <em>in situ</em> gel demonstrated superior anti-AD potency to DPZ-sol, as revealed by biochemical and histological investigations. Its potential for managing AD is suggested by the favorable outcomes of the developed and enhanced intranasal DPZ <em>in situ</em> gel.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 4","pages":" 820-840"},"PeriodicalIF":0.0,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/pm/d4pm00174e?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142434707","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":"Approaches to enhance the antimicrobial activity of carbapenems within bacterial biofilms","authors":"Matthew A. Lamb, Sandra Wiedbrauk and Kathryn E. Fairfull-Smith","doi":"10.1039/D4PM00141A","DOIUrl":"https://doi.org/10.1039/D4PM00141A","url":null,"abstract":"<p >Carbapenems are crucial antibiotics in the battle against bacterial infections, targeting both Gram-positive and Gram-negative bacteria with exceptional potency. These antibiotics are part of a group of vital ‘last resort’ antibiotics, reserved for severe infections caused by multi-drug resistant bacteria. However, their misuse poses a significant threat and the overuse of carbapenems accelerates the development of antibiotic resistance, thereby jeopardizing the efficacy of these lifesaving drugs. Another contributing factor complicating this issue is the emergence of biofilms. These complex microbial communities are encased in a polymeric matrix and contribute to the onset of serious infections which are challenging to treat. This review explores the biofilm potency of different clinically approved carbapenems, delving into the latest strategies and delivery systems employed to augment their anti-biofilm activity. The goal is to provide valuable insights into the development of more potent carbapenems specifically tailored for combating biofilms.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 4","pages":" 622-644"},"PeriodicalIF":0.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/pm/d4pm00141a?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142434714","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 progress on nanosystems for nucleic acid delivery","authors":"Shanka Walia and Mohit J. Mehta","doi":"10.1039/D4PM00009A","DOIUrl":"https://doi.org/10.1039/D4PM00009A","url":null,"abstract":"<p >Nucleic acid (NA) based therapeutics have witnessed tremendous progress and breakthroughs in treating pathological conditions, including viral infections, neurological disorders, genetic diseases, and metabolic disorders. NAs such as plasmid DNA (pDNA), short interfering RNA (siRNA), microRNA (miRNA), and antisense oligonucleotides (ASOs) can be modified to revolutionize personalized medicine. Despite the great potential of NA-based therapeutics, their clinical transformation is significantly hampered by instability, degradation, and inefficient delivery to the targeted site in the <em>in vivo</em> system. Lipid-based delivery systems hold great potential to overcome these shortcomings to enhance the delivery and bioavailability, improve stability, and increase the therapeutic effect of the NAs by delivering them to the active site. This review emphasized various nucleic acid-based therapeutics and their enhanced and improved delivery using different nanocarriers. Ultimately, the importance of lipid-based nanocarriers for delivering NAs is discussed and provides perspective in this field.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 4","pages":" 645-674"},"PeriodicalIF":0.0,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/pm/d4pm00009a?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142434715","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}