Sustained Drug Delivery Research Articles

Next-Generation Contraceptive Intravaginal Ring: Comparison of Etonogestrel and Ethinyl Estradiol In Vitro and In Vivo Release from 3D-Printed Intravaginal Ring and NuvaRing.

Intravaginal rings (IVRs) represent a well-established, woman-controlled and sustained vaginal drug delivery system suitable for a wide range of applications. Here, we sought to investigate the differences in etonogestrel (ENG) and ethinyl estradiol (EE) release from a 3D-printed IVR utilizing continuous liquid interface production (CLIP™) (referred to as CLIPLOW for low drug loading and CLIPHIGH IVRs for high drug loading) and NuvaRing, a commercially available injection molded IVR. We conducted in vitro release studies in simulated vaginal fluid to compare the release of ENG and EE from CLIPLOW IVRs and NuvaRing. CLIPLOW IVRs had a similar hormone dose to NuvaRing and exhibited slightly slower ENG release and greater EE release in vitro compared to NuvaRing. When administered to female sheep, NuvaRing demonstrated greater ENG/EE levels in plasma, vaginal tissue and vaginal fluids compared to CLIPLOW IVR despite similar drug loadings. Leveraging observed hormones levels in sheep from NuvaRing as an effective contraceptive benchmark, we developed a long-acting CLIPHIGH IVR with increased ENG and EE doses that demonstrated systemic and local hormone levels greater than the NuvaRing for 90 days in sheep. No signs of toxicity were noted regarding general health, colposcopy, or histological analysis in sheep after CLIPHIGH IVR administration. Our results provided (1) a comparison of ENG and EE release between a 3D-printed IVR and NuvaRing in vitro and in vivo, (2) a preclinical pharmacokinetic benchmark for vaginally delivered ENG and EE and (3) the generation of a 90-day CLIP IVR that will be utilized in future work to support the development of a long-acting ENG/EE IVR combined with an antiretroviral for the prevention of HIV and unplanned pregnancy.

Quantitative analysis of loxoprofen sodium loaded microspheres comprising pectin and its thiolated conjugates: In-vivo evaluation of their sustained release behavior

Continuous use of oral NSAIDs can damage mucosal membrane, which results in decreased bioavailability and non-compliance with the therapy. But the use of sustained release drug delivery systems might offer a solution. Objective was to synthesize mucoadhesive SR microspheres by using different combinations of pectin (PEC) and its thiolated derivative (T-PEC3100) for improved loxoprofen (LS) permeation. Thiolated pectin (T-PEC) was synthesized by the esterification method using thioglycolic acid. Thiolation was confirmed by thiol group quantification and charring point determination. Further characterization was done by Fourier Transform Infrared spectroscopy (FTIR), and Scanning electron microscopy (SEM). Ex-vivo mucoadhesion study was performed to confirm the improved characteristics. Microspheres (MS) were prepared using different ratios of PEC/T-PEC by solvent evaporation method and their particle size and surface morphology were evaluated. Mucus permeation study was carried out using the trans-well plate method. Sustained release behavior of prepared microspheres was investigated through the edema inhibition method in albino rats. T-PEC3100 was considered the optimum formulation for further evaluation and contained maximum thiol group content. FTIR spectra showed a characteristic peak of –SH and charring point was also changed considerably confirming the successful thiolation of PEC. SEM results showed spherical microspheres in the size range of 2–10 μm. Thiol-rich formulation of MS exhibited more than 80 % release after 12 h and maximum absorbable dose (MAD) was calculated as 400 μg % inhibition of edema in MS treated group was slowly attained initially but the reduction in inflammation was detected even after 24 h as compared to control group. Promising results from In-vivo edema inhibition study suggest the possible use of these thiolated MS in formulating sustained release formulation for arthritis.

Formulation and evaluation of Ebastine transferosomes

The present study was focused on formulating and evaluating Ebastine containing Transferosomes formulation for in vitro studies. Transferosomes formulations were prepared by using cold method and were evaluated for in vitro characteristics, stability studies. Transferosomes formulation displayed highest entrapment efficiency with desired particle size. SEM analyses showed that Transferosomes formulation was spherical in shape. Transferosomes containing lipid higher percentage of drug release after 8 h as compared to other formulations. F-2 formulation was found to be stable at the end of the study on storage condition. The present study suggested that Transferosomes gel formulations provide sustained and prolonged delivery of drug with enhance bioavailability.

Development and characterization of Decitabine Niosomes

The present study was focused on formulating and evaluating Decitabine containing niosomes formulation for In Vitro studies. Niosomal formulations were prepared by using different ratio of surfactant (Tween 80 and Tween 20) and cholesterol by thin film hydration method and were evaluated for In Vitro characteristics, stability studies. Span 20 containing niosomal formulation displayed highest entrapment efficiency with desired particle size. SEM analyses showed that niosomal formulation was spherical in shape. Niosomes containing Tween 20 displayed higher percentage of drug release after 8 h as compared to other formulations. F-7 formulation was found to be stable at the end of the study on storage condition. The present study suggested that niosomal formulations provide sustained and prolonged delivery of drug with enhance bioavailability.

Polyurea-urethane Temperature-responsive Hydrogels for Sustained Delivery of Anti-VEGF Therapeutics.

Temperature-responsive hydrogels, or thermogels, have emerged as a leading platform for sustained delivery of both small molecule drugs and macromolecular biologic therapeutics. Although thermogel properties can be modulated by varying the polymer's hydrophilic-hydrophobic balance, molecular weight and degree of branching, varying the supramolecular donor-acceptor interactions on the polymer remains surprisingly overlooked. Herein, to study the influence of enhanced hydrogen bonding on thermogelation, we synthesized a family of amphiphilic polymers containing urea and urethane linkages using quinuclidine as an organocatalyst. Our findings showed that the presence of strongly hydrogen bonding urea linkages significantly enhanced polymer hydration in water, in turn affecting hierarchical polymer self-assembly and macroscopic gel properties such as sol-gel phase transition temperature and gel stiffness. Additionally, analysis of the sustained release profiles of Aflibercept, an FDA-approved protein biologic for anti-angiogenic treatment, showed that urea bonds on the thermogel were able to significantly alter the drug release mechanism and kinetics compared to usage of polyurethane gels of similar composition and molecular weight. Our findings demonstrate the unrealized possibility of modulating gel properties and outcomes of sustained drug delivery through judicious variation of hydrogen bonding motifs on the polymer structure.

Synthesis of thermally and pH-responsive poly(2-(dimethylamino)ethyl methacrylate)-based hydrogel reinforced with cellulose nanocrystals for sustained drug release

Hydrogels are widely employed in biomedical applications due to their high swelling potential, tailored mechanical properties, biocompatibility, and ability to incorporate drugs to modify their release behavior. This study explored the synthesis of dual stimuli-responsive composite hydrogels by combining poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) with 4, 8, and 12 % (w/w) of cellulose nanocrystals (CNC) through in-situ free-radical polymerization, modifying their properties for topical anti-inflammatory release. Although PDMAEMA-based hydrogels have been known for their responsiveness to pH and temperature stimuli, which are useful for modulating the release profile of drugs, their use as a matrix for anti-inflammatory topical applications remains unexplored. Thus, a comprehensive analysis of CNC concentration's impact on PDMAEMA-based hydrogel structure and physicochemical properties is provided. The incorporation of ibuprofen as an anti-inflammatory model was assessed, providing insights into the potential of these composite hydrogels for sustained drug delivery applications. Overall, the hydrogels exhibited homogenous CNC dispersion, with gel fraction higher than 70 % and ibuprofen load higher than 90 %. The rise in CNC concentration led to an increase hydrogel stiffness. Finally, the CNC incorporation also modified the ibuprofen release to a more sustained profile, following the Peppas-Sahlin model, which may be attractive for developing pharmaceutical devices for different therapeutical scenarios.

Self-healable, stimuli-responsive bio-ionic liquid and sodium alginate conjugated hydrogel with tunable Injectability and mechanical properties for the treatment of breast cancer

Designing stimuli-responsive drug delivery vehicles with higher drug loading capacity, sustained and targeted release of anti-cancer drugs and able to mitigate the shortcomings of traditional systems is need of hour. Herein, we designed stimuli-responsive, self-healable, and adhesive hydrogel through synergetic interaction between [Cho][Gly] (Choline-Glycine) and sodium alginate (SA). The hydrogel was formed as a result of non-covalent interaction between the components of the mixture forming the fibre kind morphology; confirmed through FTIR/computational analysis and SEM/AFM images. The hydrogel exhibited excellent mechanical strength, self-healing ability, adhesive character and most importantly; adjustable injectability. In vitro biocompatibility of the hydrogel was tested on HaCaT and MCF-7 cells, showing >92 % cell viability after 48 h. The hemolysis ratio (<4 %) of the hydrogel confirmed the blood compatibility of the hydrogel. When tested for drug-loading capacity, the hydrogel show 1500 times drug loading for the 5-fluorouracil (5-FU) against the SA based hydrogel. In vitro release data indicated that 5-FU have more preference towards the cancerous cell condition, i.e. acidic pH (>85 %), whereas the drug-loaded hydrogel successfully killed the MCF-7 and HeLa cell with a <IC50–1.92 mM value. The studied hydrogel paves way towards controlled and sustained delivery of anti-cancer drug for the treatment of breast cancer.

Study of Manipulative In Situ Pore-Formation upon Polymeric Coating on Cylindrical Substrate for Sustained Drug Delivery.

Herein, the micro-porous polylactic acid coating applied on the surface of the cylindrical substrate is fabricated by a novel in situ pore-formation strategy based on the combinational effect of breath figure (BF) and vapor-induced phase separation (VIPS) processes. Under the condition of high environmental humidity, solvent pair of chloroform and dimethylformamide is employed for post-treatment onto pre-formed PLA coating to induce the pore-formation following the mechanism of BF and VIPS, respectively. A composite porous structure with both cellular-like and bi-continuous network morphologies is obtained. By tunning the experimental factors including the ratio of the solvent pair, environmental humidity, and temperature, morphological manipulation upon the pore morphology can be facilely achieved based on the control of mechanism transition between BF and VIPS. Paclitaxel is used as a model drug and loaded into the porous coating by the wicking effect of post-immersion. Coatings with different morphological features show varying drug loading and release capacities. The 28-day release test reveals dynamic release profiles between different coating samples, with the total release rate ranging from 35.70% to 79.96%. Optimal loading capacity of 19.28µg cm-2 and 28-day release rate of 35.70% are achieved for the coating with composite BF-VIPS structure. This research established a cost-efficient strategy with high flexibility in the structural manipulation concerning the construction of drug-eluting coating with the feature of manipulative drug delivery.

Transformation of Metal-Organic Framework from Kinetic to Thermodynamic Product for Controlled Delivery of Vitamin C.

A biocompatible metal-organic framework (MOF), named HSTC-4, constructed using the flexible 4,4'-oxybis(benzoic acid) (OBA), was developed to enable efficient loading and controlled release of vitamin C (VC) through a combination of strategies involving ligand length, structure design, and metal selection. The kinetic product HSTC-4 demonstrates a propensity for transforming into the thermodynamically stable HSTC-5 under external stimuli, such as photoillumination and vacuum heating, as witnessed by single-crystal to single-crystal transformation. Density functional theory (DFT) calculations reveal that the VC guest molecules exhibit stronger binding affinity with HSTC-5 due to its narrower pores compared to HSTC-4, resulting in a slower release of VC from VC@HSTC-5. Furthermore, precise control over VC release can be achieved by introducing surface modifications involving SiO2 onto the structure of VC@HSCT-5, while simultaneously adjusting environmental factors such as pH and temperature conditions. Preliminary cell culture experiments and cytotoxicity assays highlight the biocompatibility of HSTC-5, suggesting that it is a promising platform for sustained drug delivery and diverse biomedical applications.

Concentration‐driven morphology change of a self‐aggregated amino acid‐inspired fluorescence‐active copolymer for sustained release of hydrophobic drug

AbstractThe development of amphiphiles for sustained drug delivery represents a promising approach in biomedical fields. Polymeric self‐assembly with a hydrophobic core offers plenty of opportunities to encapsulate hydrophobic drugs for facilitating targeted delivery to the specific sites of action. Herein, N‐Boc tryptophan has been used to develop a hydrophobic monomer, Boc‐tryptophan‐HEMA (HBT). The HBT monomer has further been grafted on modified alginic acid through the RAFT technique to synthesize a unique amphiphilic copolymer with fluorescence characteristics. The advanced polymer chromatography demonstrates a narrow distribution curve, signifying the living nature of polymerization. The copolymer has exhibited self‐aggregation behavior with two distinct shapes at two different critical aggregation concentrations (CAC). The concentration‐dependent shape variation has been investigated using FESEM and TEM analyses, further supported by a small‐angle x‐ray scattering analysis. The self‐aggregation behavior of the copolymer facilitates the uptake of a model hydrophobic drug (naproxen) and its release in a sustained manner with varied rates at two different concentrations.

Dual phage-incorporated electrospun polyvinyl alcohol-eudragit nanofiber matrix for rapid healing of diabetic wound infected by Pseudomonas aeruginosa and Staphylococcus aureus.

Diabetic wound healing remains a healthcare challenge due to co-occurring multidrug-resistant (MDR) bacterial infections and the constraints associated with sustained drug delivery. Here, we integrate two new species of phages designated as PseuPha1 and RuSa1 respectively lysing multiple clinical MDR strains of P. aeruginosa and S. aureus into a novel polyvinyl alcohol-eudragit (PVA-EU†) nanofiber matrix through electrospinning for rapid diabetic wound healing. PVA-EU† evaluated for characteristic changes that occurred due to electrospinning and subjected to elution, stability and antibacterial assays. The biocompatibility and wound healing ability of PVA-EU† were assessed through mouse fibroblast cell line NIH3T3, followed by validation through diabetic mice excision wound co-infected with P. aeruginosa and S. aureus. The electrospinning resulted in the incorporation of ~ 75% active phages at PVA-EU†, which were stable at 25°C for 30days and at 4°C for 90days. PVA-EU† showed sustained release of phages for 18h and confirmed to be detrimental to both mono- and mixed-cultures of target pathogens. The antibacterial activity of PVA-EU† remained unaltered in the presence of high amounts of glucose, whereas alkaline pH promoted the activity. The matrix exerted no cytotoxicity on NIH3T3, but showed significant (p < 0.0001) wound healing in vitro and the process was rapid as validated through a diabetic mice model. The sustained release, quick wound closure, declined abundance of target MDR bacteria in situ and histopathological signs of recovery corroborated the therapeutic efficacy of PVA-EU†. Taken together, our data signify the potential application of PVA-EU† in the rapid treatment of diabetic wounds without the aid of antibiotics.

X-ray Opaque Polymer Drug-Eluting Beads Loaded with Iodized Oil: Preparation and In Vitro and In Vivo Evaluations.

Drug-eluting microspheres are commonly used as a local drug delivery system for interventional therapy. However, current drug-eluting microspheres have poor X-ray visibility, which can hinder tracking and postembolization evaluation. In the current study, X-ray-visible poly(acrylic acid) drug-eluting beads loaded with iodized oil (IO-PAA-DEBs) ranging from 100-300 μm were prepared and evaluated both in vitro and in vivo. Iodized oil served as the radiopaque agent, and X-ray and computed tomography scanning confirmed that the microspheres exhibited excellent X-ray-visible properties. The drug-loading capacities of bleomycin hydrochloride, doxorubicin hydrochloride, and oxaliplatin were also investigated. IO-PAA-DEBs exhibited sustained drug release properties, accompanied by a cumulative drug release rate that reached approximately 60% after 120 h. In vitro and in vivo experiments revealed that IO-PAA-DEBs had good biocompatibility. Collectively, these results demonstrated that IO-PAA-DEBs could facilitate transarterial embolization and sustained drug delivery.

A hybrid formulation of porous silicon nanoparticle with carboxymethyl cellulose for enhanced drug loading

Porous silicon nanoparticles (pSiNPs) have received considerable spotlight in drug delivery systems due to their biocompatibility, drug loading capacity, and easy surface modification. Despite these merits, the degradation rate control of pSiNPs in biological environments remains a challenge for sustained-release applications. In this study, we introduce a novel formulation of pSiNPs-based coated with carboxymethyl cellulose (pSiNPs-CMC) for the first time. The drug loading and release behavior of pSiNPs-CMC, featuring representative anticancer drugs such as doxorubicin, gemcitabine, paclitaxel, and SN-38, were extensively characterized. Notably, the CMC coating on pSiNPs resulted in an increase in loading efficiency of over 60% both for hydrophilic and hydrophobic drugs, while ensuring a controlled and tailored drug release profile. Our findings present the potential of the pSiNPs-CMC composite as a robust and versatile platform, overcoming conventional limitations in drug specificity and representing a significant advancement in sustained and personalized drug delivery systems.

Uni-directional release of ibuprofen from an asymmetric fibrous membrane enables effective peritendinous anti-adhesion

Drug-loaded porous membranes have been deemed to be effective physicochemical barriers to separate postoperative adhesion-prone tissues in tendon healing. However, cell viability and subsequent tissue regeneration might be severely interfered with the unrestricted release and the locally excessive concentration of anti-inflammatory drugs. Herein, we report a double-layered membrane with sustained and uni-directional drug delivery features to prevent peritendinous adhesion without hampering the healing outcome. A vortex-assisted electrospinning system in combination with ibuprofen (IBU)-in-water emulsion was utilized to fabricate IBU-loaded poly-ʟ-lactic-acid (PLLA) fiber bundle membrane (PFB-IBU) as the anti-adhesion layer. The resultant highly porous structure, oleophilic and hydrophobic nature of PLLA fibers enabled in situ loading of IBU with a concentration gradient across the membrane thickness. Aligned collagen nanofibers were further deposited at the low IBU concentration side of the membrane for regulating cell growth and achieving uni-directional release of IBU. Drug release kinetics showed that the release amount of IBU from the high concentration side reached 79.32% at 14 d, while it was only 0.35% at the collagen side. Therefore, fibroblast proliferation at the high concentration side was successfully inhibited without affecting the oriented growth of tendon-derived stem cells at the other side. In vivo evaluation of the rat Achilles adhesion model confirmed the successful peritendinous anti-adhesion of our double-layered membrane, in that the macrophage recruitment, the inflammatory factor secretion and the deposition of pathological adhesion markers such as α-SMA and COL-III were all inhibited, which greatly improved the peritendinous fibrosis and restored the motor function of tendon.

In Vivo Ocular Pharmacokinetics and Toxicity of Siponimod in Albino Rabbits.

Siponimod is a promising agent for the inhibition of ocular neovascularization in diabetic retinopathy and age-related macular degeneration. Siponimod's development for ophthalmological application is hindered by the limited information available on the drug's solubility, stability, ocular pharmacokinetics (PK), and toxicity in vivo. In this study, we investigated the aqueous stability of siponimod under stress conditions (up to 60 °C) and its degradation behavior in solution. Additionally, siponimod's ocular PK and toxicity were investigated using intravitreal injection of two different doses (either 1300 or 6500 ng) in an albino rabbit model. Siponimod concentration was quantified in the extracted vitreous, and the PK parameters were calculated. The drug half-life after administration of the low and high doses was 2.8 and 3.9 h, respectively. The data obtained in vivo was used to test the ability of published in silico models to predict siponimod's PK accurately. Two models that correlated siponimod's molecular descriptors with its elimination from the vitreous closely predicted the half-life. Furthermore, 24 h and 7 days after intravitreal injections, the retinas showed no signs of toxicity. This study provides important information necessary for the formulation and development of siponimod for ophthalmologic applications. The short half-life of siponimod necessitates the development of a sustained drug delivery system to maintain therapeutic concentrations over an extended period, while the lack of short-term ocular toxicity observed in the retinas of siponimod-treated rabbits supports possible clinical use.

Lactic acid and hydroxyl terminated polybutadiene assisted synthesis of vegetable oil based polyurethanes for sustained drug delivery systems

The present research aims to develop a series of biodegradable, sustainable and biocompatible, polyurethanes (PU–S1 to PU-S4). The synthesis of these polyurethanes involved a combination of different ratios of an epoxidized polyol (followed by ring opening with ethanol) extracted from soybean oil, along with hydroxyl-terminated polybutadiene (HTPB). The lactic acid was esterified with ethylene glycol to produce a sustainable chain extender which was used to increase the molecular weight of the final polymer. FTIR spectroscopy and scanning electron microscopy (SEM) were used for the characterization of the PU samples. The thermal degradation behavior and wetting ability of the PUs were also determined through contact angle, indicating a gradual decrease in hydrophilicity with increasing HTPB content finally made a little hydrophobic surface in the case of PU-S4 sample (contact angle = 96.46°). The potential of these polyurethanes (PUs) as drug delivery systems was checked using gabapentin as a prototypical drug. It was dispersed into the polymer matrix via the solvent evaporation process. The analysis of drug release adhered to US Pharmacopeial guidelines was determined using 0.06 N HCl as the release medium. Sample PU-S4 showed a higher drug release, reaching 56.0 % after 6 h. Additionally, a regular trend was observed in different PU samples, suggesting an increase in HTPB content with a decrease in drug release.

Advances in Drug Delivery Systems

Drug delivery systems have undergone remarkable advancements in recent years, revolutionizing the way therapeutic agents are administered and enhancing their efficacy and safety profiles. This review explores the latest developments in drug delivery technologies, including biodegradable polymers, nanocarriers, and smart delivery systems responsive to specific physiological conditions. Nanotechnology-based delivery platforms, such as liposomes, dendrimers, and polymeric nanoparticles, have demonstrated impressive potential in improving drug targeting, bioavailability, reducing adverse effects, and facilitating controlled release. The increasing use of biodegradable polymers like poly(glycolic acid) (PGA) and poly(lactic acid) (PLA) enables localized and sustained drug delivery. Smart delivery systems employing stimuli-responsive materials enable drug release triggered by environmental cues like pH, temperature, and enzyme activity. Furthermore, the integration of personalized medicine and advanced drug delivery technologies is enabling more efficient and tailored therapeutic approaches. This review highlights the prevailing trends, challenges, and future prospects in drug delivery systems, emphasizing their pivotal role in advancing next-generation therapies

Efficacy and safety of dendrimer-enhanced (DEP) cabazitaxel (DEP CTX) in patients with advanced solid cancers in a phase 1/2 trial (P1/2).

3004 Background: DEP CTX is a highly optimized dendrimer nanoparticle formulation of cabazitaxel that achieves sustained cytotoxic drug delivery to tumors via enhanced permeability &amp; retention effects. Unlike standard cabazitaxel (s-CTX), DEP CTX is highly water soluble, does not contain toxic excipients associated with anaphylaxis &amp; does not require steroid/antihistamine premedication. We report the final P2 efficacy and safety results in patients (pts) with advanced/metastatic solid tumors. Methods: Pts were treated with DEP CTX at 20 mg/m2 cabazitaxel, IV 3-weekly. Efficacy was assessed by RECIST v1.1, Prostate Cancer Working Group 3 (PCWG3) guidelines or serum tumor markers; evaluable pts had relevant criteria at baseline and a follow-up assessment per protocol window. Safety was assessed by CTCAE v4.03. (EudraCT 2017-003424-76). Results: In P2, 75 pts were enrolled, prioritizing metastatic castration-resistant prostate cancer (mCRPC, s-CTX’s only approved indication), esophagogastric (EG) &amp; ovarian (OV) cancers. For all pts, median progression free survival (mPFS) and overall survival (mOS) were 3.8 and 9.0 mths, respectively. Objective response rate (ORR) was 20% in 45 evaluable pts. All 25mCRPC pts were heavily pre-treated with a median of 4 prior lines of anticancer treatment. mPFS was 4.4 mths (radiographic or prostate specific antigen [PSA]); mOS was 14.7 mths. The disease control rate (DCR) was 70.6%; ORR was 16.7%. PSA reduced in 90% pts (by &gt; 50% in 52.4%); 87% with bone metastases had no progression or improved. Of 15 EG pts, 9 were adenocarcinoma (ADENO) (3 gastric, 2 esophageal &amp; 4 EG junction) &amp; 6 were esophageal squamous cell carcinoma (SCC). For all EG pts, mPFS was 4.0 mths, mOS was 8.6 mths. mPFS was 4.0/1.9 mths for ADENO/SCC, respectively. Overall, DCR was 80%; ORR 30%. DCR was 100%/50% and the ORR was 33%/25% for ADENO/SCC, respectively. Of 22 OV pts, 96% were platinum resistant (Pt-R), with a median of 4 prior lines of anticancer treatment, including 59% with ≥ 3 platinum lines. mPFS/mOS were 3.1 mths &amp; not reached, respectively. DCR was 66.7%; ORR 17.6%. Treatment related adverse events (TRAEs) were mostly mild/moderate (grade (G) 1/2; 64%/25%). Only 21% of pts had G 3/4 non-hematological TRAEs, while G3/4 lab detected neutropenia was seen in only 23% of pts despite no routine G-CSF. TRAEs observed in ≥10% of pts included fatigue, neutropenia, anemia, thrombocytopenia, diarrhea, nausea, vomiting, peripheral neuropathy and decreased appetite. Conclusions: DEP CTX exhibited clinically meaningful, durable antitumor activity in multiple advanced solid cancers, including mCRPC, Pt-R OV and EG cancers without the need for steroid premedication. The antitumor activity &amp; safety results compare favorably to s-CTX, or standard of care chemotherapy in non-prostate cancers, and highlight the promising potential of dendrimer-enhanced delivery of cabazitaxel. Clinical trial information: 2017-003424-76 .

A Comparative DFT Investigation of the Adsorption of Temozolomide Anticancer Drug over Beryllium Oxide and Boron Nitride Nanocarriers.

Herein, attempts were made to explore the adsorption prospective of beryllium oxide (Be12O12) and boron nitride (B12N12) nanocarriers toward the temozolomide (TMZ) anticancer drug. A systematic investigation of the TMZ adsorption over nanocarriers was performed by using quantum chemical density functional theory (DFT). The favorability of Be12O12 and B12N12 nanocarriers toward loading TMZ was investigated through A↔D configurations. Substantial energetic features of the proposed configurations were confirmed by negative adsorption (E ads) energy values of up to -30.47 and -26.94 kcal/mol for TMZ•••Be12O12 and •••B12N12 complexes within configuration A, respectively. As per SAPT results, the dominant contribution beyond the studied adsorptions was found for the electrostatic forces (E elst = -100.21 and -63.60 kcal/mol for TMZ•••B12N12 and •••Be12O12 complexes within configuration A, respectively). As a result of TMZ adsorption, changes in the energy of molecular orbitals followed by alterations in global reactivity descriptors were observed. Various intermolecular interactions within the studied complexes were assessed by QTAIM analysis. Notably, a favorable adsorption process was also observed under the effect of water with adsorption energy ( reaching -28.05 and -22.26 kcal/mol for TMZ•••B12N12 and •••Be12O12 complexes within configuration A, respectively. The drug adsorption efficiency of the studied nanocarriers was further examined by analyzing the IR and Raman spectra. From a sustained drug delivery point of view, the release pattern of TMZ from the nanocarrier surface was investigated by recovery time calculations. Additionally, the significant role of doping by heavy atoms (i.e., MgBe11O12 and AlB11N12) on the favorability of TMZ adsorption was investigated and compared to pure analogs (i.e., Be12O12 and B12N12). The obtained data from thermodynamic calculations highlighted that the adsorption process over pure and doped nanocarriers was spontaneous and exothermic. The emerging findings provide a theoretical base for future works related to nanocarrier applications in the drug delivery process, especially for the TMZ anticancer drug.

From biopolymer matrix to medicine: the drug delivery dynamics of amoxicillin-loaded PVA/SA/ZnONPs hydrogels

This research presents a comprehensive study of Polyvinyl alcohol/Sodium alginate/Zinc oxide nanoparticles (PVA/SA/ZnONPs) and PVA/SA/ZnONPs/Amoxicillin (AMX) hydrogels, demonstrating their potential for various biomedical applications. A comparative analysis of their swelling behavior, in vitro biodegradation, antibacterial properties, and drug release profiles was performed. The hydrogels demonstrated distinct swelling characteristics, with the PVA/SA/ZnONPs/AMX hydrogel showing a higher initial swelling ratio. This behavior, likely due to the increased hydrophilicity from AMX, subsequently decreased over time, indicating AMX release into the environment. The biodegradation study highlighted a faster degradation rate for the PVA/SA/ZnONPs/AMX hydrogel, suggesting its suitability for applications requiring rapid degradation, such as drug delivery systems. Regarding antibacterial properties, the PVA/SA/ZnONPs/AMX hydrogel showed significant antibacterial activity against both Escherichia coli and Staphylococcus aureus, making it a strong candidate for biomedical applications necessitating antibacterial activity. Additionally, the drug release study presented a gradual and controlled release of AMX from the hydrogels over time, demonstrating their potential for sustained drug delivery applications. This research underscores the potential of PVA/SA/ZnONPs/AMX hydrogel, particularly for biomedical applications, especially in wound healing and drug delivery domains, given its potent antibacterial properties and controlled drug release behavior.