RSC Pharmaceutics最新文献

{"title":"Comparison of emulsion and spray methods for fabrication of rapamycin-loaded acetalated dextran microparticles†","authors":"Stephen A. Ehrenzeller, Nicole Rose Lukesh, Rebeca T. Stiepel, Denzel D. Middleton, Steven M. Nuzzolo, Aliyah J. Tate, Cole J. Batty, Eric M. Bachelder and Kristy M. Ainslie","doi":"10.1039/D4PM00054D","DOIUrl":"https://doi.org/10.1039/D4PM00054D","url":null,"abstract":"<p >Rapamycin (rapa), an immunosuppressive medication, has demonstrated considerable effectiveness in reducing organ transplant rejection and treating select autoimmune diseases. However, the standard oral administration of rapa results in poor bioavailability, broad biodistribution, and harmful off-target effects, necessitating improved drug delivery formulations. Polymeric microparticles (MPs) are one such solution and have demonstrated promise in pre-clinical studies to improve the therapeutic efficacy of rapa. Nevertheless, MP formulations are highly diverse, and fabrication method selection is a critical consideration in formulation design. Herein, we compared common fabrication processes for the development of rapa-loaded MPs. Using the biopolymer acetalated dextran (Ace-DEX), rapa-loaded MPs were fabricated by both emulsion (homogenization and sonication) and spray (electrospray and spray drying) methods, and resultant MPs were characterized for size, morphology, surface charge, and drug release kinetics. MPs were then screened in LPS-stimulated macrophages to gauge immunosuppressive efficacy relative to soluble drug. We determined that homogenized MPs possessed the most optimal combination of sizing, tunable drug release kinetics, and immunosuppressive efficacy, and we subsequently demonstrated that these characteristics were maintained across a range of potential rapa loadings. Further, we performed <em>in vivo</em> trafficking studies to evaluate depot kinetics and cellular uptake at the injection site after subcutaneous injection of homogenized MPs. We observed preferential MP uptake by dendritic cells at the depot, highlighting the potential for MPs to direct more targeted drug delivery. Our results emphasize the significance of fabrication method in modulating the efficacy of MP systems and inform improved formulation design for the delivery of rapa.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 4","pages":" 727-741"},"PeriodicalIF":0.0,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/pm/d4pm00054d?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142434720","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":"Pharmaceutical salts of azole anti-fungal drugs: physicochemical behaviour and activity studies†","authors":"Hafsa Qadri, Asif A. Malik, Aadil A. Ahangar, Manzoor Ahmad Mir, Ajiaz A. Dar and Abdul Haseeb Shah","doi":"10.1039/D4PM00003J","DOIUrl":"https://doi.org/10.1039/D4PM00003J","url":null,"abstract":"<p >Pharmaceutical cocrystal engineering is a potential and growing strategy for modulating the physicochemical and pharmacokinetic properties of drug molecules. This study aims to study the new solid forms of miconazole (MIC) and ketoconazole (KTC) prepared through the crystal engineering method of crystallization. Utilizing the understanding of the sulfonate-pyridinium synthon, molecular salts of MIC and KTC with naphthalene disulfonic acid (NDSA-2H) have been prepared and characterized through thermal, spectroscopic, microscopic, and diffraction methods. Both molecular salts, <em>i.e.</em>, MIC-C and KTC-C, have been obtained as crystalline solids and their phase purity and formation have been established through diffraction studies. The new drug forms exhibit augmented thermal stability and aqueous solubility. Powder dissolution studies in an aqueous medium at pH 2 and pH 7 indicate a significant increase in thermal stability and aqueous solubility of the new drug forms compared to their drug precursors. Structural investigation of MIC-C validates the formation of the ionic sulfonate-pyridinium synthon involving proton transfer resulting in charge development, leading to enhancement in the physicochemical properties. <em>In vitro</em> studies show that KTC-C in addition to retaining most of the biological activities possesses antifungal potential comparable to that of the standard drug since it inhibited the growth of tested <em>Candida</em> strains without showing enhancement in host toxicity. Both the designed salts exhibit fluorescence properties inside <em>Candida</em> cells (in contrast to the standard drugs).</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 4","pages":" 705-715"},"PeriodicalIF":0.0,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/pm/d4pm00003j?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142434718","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 leucine as an aerosolization enhancer on the bioactivity of spray dried viral-vectored vaccines for inhalation","authors":"Varsha Singh, Myrna Dolovich, Zhou Xing, Emily D. Cranston and Michael R. Thompson","doi":"10.1039/D4PM00079J","DOIUrl":"https://doi.org/10.1039/D4PM00079J","url":null,"abstract":"<p >Aerosolization enhancers, like <small>L</small>-leucine, can improve deep-lung deposition of inhalable dry powders although the implications of their use have not yet been evaluated for sensitive biologics like viral vectored vaccines. This study investigates the effect of <small>L</small>-leucine concentrations (0–50 wt%) as an added component to the viral-encapsulating matrix comprised of mannitol and dextran, on aerosolization relative to bioactivity of spray dried human serotype 5 adenovirus. Modelling the intended purpose of inhalation, the aerodynamic properties (fine particle fraction and mass median aerodynamic diameter) of the powders were analyzed using a Next Generation Impactor. Overall, increasing the <small>L</small>-leucine concentration in the spray dried formulations improved the fine particle fraction (&gt;40%) and reduced the aerodynamic diameter (&lt;5 μm). However, bioactivity was negatively affected by the presence of <small>L</small>-leucine in the formulation and that demanded deeper investigation. The root cause for the declining bioactivity was finally attributed to aggregation of the adenovirus induced by <small>L</small>-leucine in the feed solution prior to spray drying, which was determined using a qViro-X particle counter. The intent of this study was to emphasize that advantages and disadvantages will exist with additives like an aerosolization enhancer, for this relatively new class of vaccines.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 4","pages":" 775-785"},"PeriodicalIF":0.0,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/pm/d4pm00079j?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142434703","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":"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}