{"title":"Preparation, characterization and drug release properties of 5-(p-carboxyphenoxy) valeric anhydride microspheres loaded with nimodipine.","authors":"Sibo Su, Jingguo Liu, Yongxue Guo","doi":"10.1080/10837450.2025.2559719","DOIUrl":"10.1080/10837450.2025.2559719","url":null,"abstract":"<p><p>Nimodipine (NMP), a poorly water-soluble small-molecule agent, demonstrates notable therapeutic limitations in addressing cerebral vasospasm secondary to subarachnoid hemorrhage (SAH). Owing to its inherent physicochemical properties characterized by low oral bioavailability, rapid elimination half-life, and extensive first-pass metabolism, conventional formulations necessitate frequent dosing regimens to sustain therapeutic plasma concentrations. These pharmacological challenges collectively result in suboptimal patient adherence, marked plasma concentration fluctuations, and recurrent vascular irritation. To overcome these pharmacological constraints, this investigation engineered a novel drug-loaded microsphere system utilizing poly(5-(p-carboxyphenoxy) valeric anhydride (Poly(CPV)) as a biodegradable matrix material. The sustained-release microspheres were fabricated <i>via</i> microfluidic technology to systematically address the clinical challenges associated with frequent dosing regimens. The optimized microspheres exhibited a drug loading capacity of 5.59%, an encapsulation efficiency of 70.22%, and a uniform particle size distribution (43.98 ± 4.29 μm). <i>In vitro</i> release studies demonstrated sustained drug release over 14 days. Pharmacokinetic evaluation in rats revealed that the NMP-loaded microspheres maintained relative stable plasma drug concentrations for approximately 10 days. Biocompatibility assessments, including histocompatibility tests and <i>in vitro</i> cytotoxicity assays, confirmed the excellent biocompatibility of the Poly(CPV) microsphere. These findings suggest that Poly(CPV)-based microspheres prepared by microfluidics represent a promising drug delivery platform for poorly soluble small-molecule pharmaceuticals, offering controlled release characteristics and improved therapeutic outcomes.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1-16"},"PeriodicalIF":2.5,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marwa H Abdo, Marwa A Abd El-Fattah, Heba A Eassa, Manal K Darwish
{"title":"D-optimal design-based optimization of etoricoxib cubogel for management of arthritis; in vitro and in vivo evaluation.","authors":"Marwa H Abdo, Marwa A Abd El-Fattah, Heba A Eassa, Manal K Darwish","doi":"10.1080/10837450.2025.2556062","DOIUrl":"10.1080/10837450.2025.2556062","url":null,"abstract":"<p><p>Etoricoxib (Et) is selective COX-2 inhibitor with several drawbacks after oral administration. Current study focused on formulating targeted Et cubogel for osteoarthritis management. Interaction between formulation factors; (glyceryl-monooleate (GMO) and Poloxamer407 (Px)) concentrations and process parameters (melting/solvent-evaporation preparation methods) was investigated using D-optimal design. Considered levels were 3, 5 and 7% for GMO and 0.5,0.75 and 1% for Px. Effect of selected variables on particle size (PS) and entrapment efficiency (EE) of Et cubosomes was studied using Design Expert software. Optimized formulation was studied for zeta potential, TEM, and Et release. Optimum formula was loaded into gel formulations and subjected to physical characterization and in-vitro Et release. Selected cubogel was evaluated for ex-vivo permeation, and anti-inflammatory activity using carrageenan-induced edema model. Optimum formulation (6.5% GMO,1% Px , melting preparation method) had PS of 58.6 ± 0.51 nm, EE of 96.1 ± 1.5%, zeta potential of -26.6 ± 0.66 mV and cubic structure as indicated by TEM. Formulated cubogels had acceptable physical properties with sustained release depending on gelling agent type and concentration. Ex-vivo permeation confirmed higher permeability for Et cubogel than Etgel. Anti-inflammatory study confirmed enhanced (<i>p</i> < 0.05) anti-inflammatory activity of Et cubogel as compared to Et gel. Hence, the present study presents Et cubgel formulation as anti-inflammatory remedy.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1-14"},"PeriodicalIF":2.5,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Formulation and evaluation of buccal films loaded with insulin encapsulated in glucose responsive amphiphilic dendrimer micelles.","authors":"Dana R Dweekat, Suhair S Al-Nimry, Ayat A Bouzieh","doi":"10.1080/10837450.2025.2556060","DOIUrl":"10.1080/10837450.2025.2556060","url":null,"abstract":"<p><p>The objective was to prepare a mucoadhesive buccal film containing amphiphilic dendrimer micelles nanoparticles (APD micelles NPs) loaded with insulin. The APD micelles NPs were synthesized by a series of chemical reactions followed by self-assembly. Insulin loading was done by mixing insulin with APD micelles solution. A mucoadhesive buccal film was prepared using solvent casting method. Stability of the buccal film after 3 months of storage in a refrigerator was investigated in terms of viscosity, drug loading, FTIR, <i>in vitro</i> drug release and morphology. The APD micelles NPs had good encapsulation efficiency and good loading capacity. FTIR results showed no interaction with the drug. <i>In vitro</i> release of insulin was glucose sensitive, increasing with time and with glucose levels and sustained for 8-10 h. The Loaded buccal film showed good physical appearance, excellent folding endurance, good mucoadhesive and tensile strength, neutral surface pH, acceptable thickness and weight. Insulin release from buccal film was not affected by the extra barrier. The stability study indicated that the film did not show any changes. In conclusion, APD micelles NPs were able to control insulin release according to glucose levels. The buccal film is expected to enhance the bioavailability of insulin compared to oral administration.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1-12"},"PeriodicalIF":2.5,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nouran M Atia, Hebatallah S Barakat, Heba A Hazzah, Rania G Ali, Ossama Y Abdallah
{"title":"Strontium alginate hybrid (inorganic/organic) nanoparticles as a novel promising nanosystem for bone regeneration: in-vitro optimization and in-vivo assessment.","authors":"Nouran M Atia, Hebatallah S Barakat, Heba A Hazzah, Rania G Ali, Ossama Y Abdallah","doi":"10.1080/10837450.2025.2556058","DOIUrl":"10.1080/10837450.2025.2556058","url":null,"abstract":"<p><p>Strontium (Sr) is a bone-seeking element characterized by its dual function of stimulating bone growth and preventing bone resorption. On the other hand, alginates (Alg) have distinct physicochemical characteristics from other natural polysaccharides because of their ability to encapsulate proteins and drugs. This work aimed to prepare novel hybrid inorganic/organic strontium alginate (Sr-Alg) nanoparticles for use as a targeting ligand in bone regeneration. These hybrid nanoparticles were prepared by a simple precipitation technique and different formulation variables were studied. The optimized formulation showed the most promising particle size (133.80 ± 2.40 nm) and zeta potential (-31.5 ± 1.45 mV). Moreover, the selected formulation was subjected to characterization using FTIR and X-ray diffraction to confirm the formation of the hybrid structure. The selected formulation was subjected to an <i>in vivo</i> study and compared with calcium alginate nanoparticles. Mice treated with Sr-containing formulation showed significant improvement in Ca/P and Ca + Sr/P ratios reached 1.799 ± 0.01 and 1.89 ± 0.01, respectively. An <i>in vivo</i> toxicity study was also assessed based on biochemical assays and histological examination of liver and kidney tissues and confirmed that non-significant nephrotoxic or hepatotoxic effects were demonstrated in the treated groups. Therefore, Sr-Alg could be considered a promising targeted ligand for bone regeneration with enhanced safety and efficacy.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1064-1081"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Samantha Mabvira, Sandile M Khamanga, Roderick B Walker
{"title":"Formulation and characterization of a fixed-dose microemulsion containing efavirenz, emtricitabine, and tenofovir.","authors":"Samantha Mabvira, Sandile M Khamanga, Roderick B Walker","doi":"10.1080/10837450.2025.2537128","DOIUrl":"10.1080/10837450.2025.2537128","url":null,"abstract":"<p><p>Despite a marked decrease in HIV/AIDS-related mortality, HIV remains one of the leading causes of death in specific populations. Despite concerted efforts to find a cure for HIV, to date, none exists. Current antiretroviral therapy inhibits replication of the virus without completely eradicating it. The successful inhibition of viral replication is only achieved using a combination of antiretrovirals, which inhibit viral replication at different stages of the HIV lifecycle. Efavirenz (EFV), emtricitabine (FTC), and tenofovir disoproxil fumarate (TDF) is one combination used for HIV management. The development of a novel fixed-dose microemulsion formulation of EFV, FTC, and TDF was undertaken. Microemulsions (ME) were manufactured using phase titration and drug loading, particle size, transparency, Zeta potential, and pH were determined. Transmission Electron Microscopy was used to visualize the microemulsion. <i>In vitro</i> release testing was used to evaluate active pharmaceutical ingredient release behavior. The optimized ME had an average Zeta potential of 33.8 mV and droplet size of 117 nm, determined using Dynamic Light Scattering and confirmed using Transmission Electron Microscopy. Powder X-ray diffraction and Differential Scanning Calorimetry analysis revealed the presence of a molecular dispersion of drugs. These findings demonstrate the potential value of using ME as a fixed-dose combination technology for the delivery of EFV, FTC, and TDF.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"923-938"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mohadese Sheikhhosseini, Sara Soltanian, Neda Mohamadi
{"title":"Co-delivery of doxorubicin and piperine using niosomes exhibited enhanced cytotoxic and inhibitory effect on cancer stem cell markers in breast cancer cells.","authors":"Mohadese Sheikhhosseini, Sara Soltanian, Neda Mohamadi","doi":"10.1080/10837450.2025.2545486","DOIUrl":"10.1080/10837450.2025.2545486","url":null,"abstract":"<p><p>Combination therapy with chemotherapy and phytochemical drugs is a promising cancer treatment method. In this study, noisome with Tween 20, span 40 and cholesterol in 80:20 ration was prepared for co-delivery of piperine (PIP) and doxorubicin (DOX) (Nio-DOX/PIP) using thin-layer hydration method. Niosomes indicated spherical structure, average size 653 ± 3.25 nm and a zeta potential of ∼-15.88 mV with an encapsulation efficiency of 84.15% and 67.50% for DOX and PIP, respectively. Release of DOX (69.25%) and PIP (35.10%) after 24 h from niosomal dispersion is less than free solution that indicate release of drug in a sustained way from niosomes. Combination index and isobologram analysis using CompuSyn software indicated that combination of DOX and PIP at IC<sub>50</sub> concentration generated synergism anticancer effect (CI value <0.9). Nio-DOX/PIP (IC<sub>50</sub>: 0.14/14 µM) exhibited greater inhibitory effect on viability of MCF-7 cells in comparison with free drugs (IC<sub>50</sub>: 0.67/67 µM). Expression analysis using Real time PCR showed that Nio-DOX/PIP reduces expression of CD133 and ABCB (33-fold), CD44 (10-fold), ALDH1: (5.8-fold) and NANOG and SOX2 (more than 90%) significantly more than free DOX. In conclusion, results showed that PIP can potentiate cytotoxicity of DOX and niosomes are suitable carriers for encapsulation of PIP and DOX.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1015-1035"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alegre Flores-Pérez, Rosa Maria Angeles-Villegas, Angélica Villanueva-Martínez, Norma L Delgado-Buenrostro, Yolanda I Chirino, María Guadalupe Nava-Arzaluz, Elizabeth Piñón-Segundo, Adriana Ganem-Rondero
{"title":"Thermosensitive hydrogel with nanostructured lipid carriers (NLC) for the topical administration of curcuminoids, resveratrol, and piperine intended for the treatment of psoriasis.","authors":"Alegre Flores-Pérez, Rosa Maria Angeles-Villegas, Angélica Villanueva-Martínez, Norma L Delgado-Buenrostro, Yolanda I Chirino, María Guadalupe Nava-Arzaluz, Elizabeth Piñón-Segundo, Adriana Ganem-Rondero","doi":"10.1080/10837450.2025.2544574","DOIUrl":"10.1080/10837450.2025.2544574","url":null,"abstract":"<p><p>Chronic inflammatory conditions, such as psoriasis, require effective therapeutic strategies to manage both local and systemic inflammation. This study aimed to develop a thermosensitive hydrogel (Gel) based on Pluronic F127 and F68, incorporating NLC (Gel-NLC) loaded with anti-inflammatory phytochemicals, such as curcuminoids, resveratrol, and/or piperine, for the topical treatment of psoriasis. Phytochemicals-loaded NLC presented encapsulation efficiency > 90%, particle size values between 39-49 nm, and polydispersity indices <0.211. Compared to curcuminoids and resveratrol from NLC and Gel-NLC, piperine alone or in combination with other phytochemicals showed superior release and transdermal flux both <i>in vitro</i> and <i>ex vivo</i>. Simultaneous encapsulation of resveratrol and piperine significantly decreased the permeation of the former, while an increase in the permeation of piperine was observed when combined with curcuminoids or resveratrol. Confocal microscopy analysis revealed that curcuminoids displayed the highest retention in the skin when encapsulated in NLC as a single agent, followed by resveratrol and piperine. These variations can be attributed to their physicochemical properties. The developed formulations are presented as effective delivery systems that can enhance the availability of these phytochemicals, thereby increasing their anti-inflammatory potential in the treatment of psoriasis.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"953-978"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144964695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joseph Della Rocca, Cory Bottone, Majid Mahjour, Katherine DiFelice, Angela Wagner, Lee J Klein, Zhen Liu, Ashish Punia, Wei Zhu, Andrew Latham, Robert Saklatvala, John Higgins, W Peter Wuelfing, Wei Xu
{"title":"Rational design and relative bioperformance of high drug load grazoprevir amorphous nanoparticle formulations.","authors":"Joseph Della Rocca, Cory Bottone, Majid Mahjour, Katherine DiFelice, Angela Wagner, Lee J Klein, Zhen Liu, Ashish Punia, Wei Zhu, Andrew Latham, Robert Saklatvala, John Higgins, W Peter Wuelfing, Wei Xu","doi":"10.1080/10837450.2025.2544571","DOIUrl":"10.1080/10837450.2025.2544571","url":null,"abstract":"<p><p>This work looked to determine if a rationally designed amorphous nanoparticle formulation of Grazoprevir (GZP) could provide a benefit over its amorphous dispersion formulation by either enabling superior bioperformance or accessing higher drug loadings. GZP-ethylcellulose nanoparticles were created at two different drug loadings (33 and 66%) by high-pressure homogenization. The GZP-ethylcellulose nanoparticles could rapidly release the drug, but neither system could match the extent of release of the amorphous dispersion. This limited extent of release led to the GZP-ethylcellulose nanoparticle formulations failing to present equivalent performance as the amorphous solid dispersion formulation in dog PK studies. Two GZP- HPMCAS-L nanoparticle formulations (50/50 GZP/HPMCAS-L and 45/45/10 GZP/HPMCAS-L/SLS) were made by a coprecipitation process followed by spray drying. These materials were analyzed and found to be composed of nanoparticles of pure amorphous drug which is stabilized by the excipients. This was confirmed by characterization techniques such as ultracentrifugation and FIB-SEM. Bio-relevant dissolution experiments demonstrated that both formulations could match the extent of drug release of the GZP amorphous dispersion formulation, but only the 45/45/10 GZP/HPMCAS-L/SLS could match the rate of release of the amorphous dispersion. The 45/45/10 GZP/HPMCAS-L/SLS nanoparticle formulation and the amorphous dispersion formulation were evaluated in a dog PK study, with the 45/45/10 GZP/HPMCAS-L/SLS formulation provided equivalent PK. These results highlight the potential benefit of directly designed nanoparticle formulations to maximize formulation bioperformance at higher drug loadings or to enable smaller dosage forms.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"939-952"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144795069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Esraa A Shetaa, Mona F Arafa, Sally E Abu-Risha, Gamal M El Maghraby
{"title":"Development of sustained release oral disintegrating tablet of fluvoxamine maleate.","authors":"Esraa A Shetaa, Mona F Arafa, Sally E Abu-Risha, Gamal M El Maghraby","doi":"10.1080/10837450.2025.2546942","DOIUrl":"10.1080/10837450.2025.2546942","url":null,"abstract":"<p><p>Fluvoxamine maleate is efficient in treatment of depression and obsessive-compulsive disorder. However, it has several side effects which are believed to be minimized by administration of slow-release formulation. This work introduces geriatric friendly rapidly disintegrating sustained release (RDSR) tablets for fluvoxamine intraoral administration. Fluvoxamine was subjected to wet co-processing with increasing weight ratios of Eudragit S100 in presence and absence of avicel. Fluvoxamine release was monitored using continuous pH variation strategy using USP II dissolution apparatus. Formulations exhibiting acceptable sustained release pattern were subjected to different investigations. Optimized systems were fabricated as RDSR tablets. Optimized systems were also assessed <i>in vivo</i> using forced swimming test using albino rats. Incorporation of avicel in the co-processed formulations showed faster release with avicel-free systems sustaining fluvoxamine release. Optimum formulations contained fluvoxamine and Eudragit at weight ratios of 4:12 (F2), 4:15 (F4) and 4:16 (F6) liberated the drug with release efficiency of 61.65, 41.76 and 34.5%, respectively. Thermal analysis and XRD reflected dispersion of fluvoxamine in amorphous form in Eudragit with no significant chemical interaction being reflected from FTIR. The developed RDSR tablets showed acceptable sustained release. <i>In vivo</i> studies reflected the superiority of sustained release systems compared to unprocessed fluvoxamine. The study developed RDSR tablets for sustained delivery of fluvoxamine.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1036-1046"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Novel vanillic acid-loaded <i>in situ</i> gels: development, characterization, <i>in vitro</i> evaluation for enhanced wound healing and skin irritation test.","authors":"Gökçe Mutlu Sonat, Emre Şefik Çağlar, Dilara Güreşçi, Ahmet Aydın, Hande Sipahi, Neslihan Üstündağ Okur","doi":"10.1080/10837450.2025.2534867","DOIUrl":"10.1080/10837450.2025.2534867","url":null,"abstract":"<p><p>This study aimed to develop <i>in situ</i> gel formulations containing vanillic acid to enhance patient compliance and accelerate wound healing. Vanillic acid-loaded <i>in situ</i> gels were prepared, and their physicochemical properties were evaluated through <i>in vitro</i> release and <i>ex vivo</i> permeation studies. Additionally, antioxidant capacity, cytotoxicity, wound healing, prostaglandin E2 levels, IL-6 inhibition, and skin irritation tests were conducted. The optimized IN3-VA formulation exhibited a gelling temperature of 32.394 ± 0.842, a pH value of 4.780 ± 0.010 and a viscosity of 2473.33 ± 11.54 cP. It demonstrated specific mechanical properties, including hardness of 27.94 ± 1.30 g and adhesiveness of -97.00 ± 14.60 g.mm. The IN15-VA formulation showed improved parameters, with a hardness of 38.84 ± 3.33 g, adhesiveness of -126.35 ± 22.78 g.mm, pH value of 4.870 ± 0.010, viscosity of 3853.33 ± 30.55 cP, and a gelling temperature of 31.854 ± 0.345. Both formulations demonstrated sustained release behavior, releasing 60% of the medication <i>in vitro</i> over 6 h with no cytotoxic effects. They also decreased copper ion reduction and the release of nitric oxide, with cellular proliferation rates of 63% for IN3-VA and 73% for IN15-VA. Moreover, IN15-VA significantly reduced prostaglandin E2 levels, controlled IL-6 increase, and exhibited non-irritating properties. The results suggest that these vanillic acid-loaded <i>in situ</i> gels hold promising potential in wound treatment due to their sustained release over 48 h.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"905-922"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}