Extended Release Profile Research Articles

Novel nanoformulation for enhanced amphotericin B efficacy and sustained release using vetiver root cellulose nanofibers against Candida albicans

The formidable antifungal agent, Amphotericin B, is well-known for its potency; however, its clinical application has been significantly limited due to toxicity and poor solubility. This study aims to address these challenges by developing and evaluating a novel nano-cellulose-based formulation of Amphotericin B to enhance its efficacy. Amphotericin B was encapsulated within cellulose nanofibers at varying ratios to optimize formulation parameters, including drug concentration, particle size, zeta potential, and entrapment efficiency. Notably, a composition ratio of 10:1 of cellulose nanofibers to Amphotericin B achieved an impressive encapsulation efficiency of 96.64 %. Subsequent physicochemical characterizations employing techniques such as FTIR, DLS, XRD, and SEM provided insights into structural attributes and interactions within formulation. Controlled and extended-release profiles were observed at various physiological pH levels, with the Korsmeyer-Peppas model showing the highest correlation, indicating predominant drug diffusion. Importantly, nanoformulation demonstrated non-toxicity to A431 cells and human erythrocytes up to a maximum concentration of 20 μg/ml, as corroborated by MTT and hemolysis assays. Furthermore, antimicrobial susceptibility and efficacy assessments, conducted using agar diffusion and broth micro-dilution methods, revealed enhanced inhibition of Candida albicans growth. The nanoformulation produced a larger zone of inhibition (DIZ) of 19.66 mm compared to a DIZ of 16.33 mm for Amphotericin B alone. Impressively, the nanoformulation exhibited a minimum inhibitory concentration (MIC) of 25 μg/ml against Candida albicans, underscoring its heightened efficacy. Additionally, the formulation's ability to improve the targetability and bioavailability of Amphotericin B holds promise for enhancing its antifungal effectiveness while reducing associated toxicity.

HPMC Extended-Release Multi-Composite Matrix for Co-delivery of Oxcarbamazepine and Vitamin D.

Background: Carbamazepine (CBZ) is considered as first-line treatment for epilepsy. The literature has signified a history of non-uniform drug performance and clinical failures. However, many studies suggested that Oxcarbazepine (OXC), a structural analog of CBZ, may have an equivalent antiepileptic effect. OXC follows a different metabolic pathway other than CBZ. However, both share the same mechanism of action by blocking voltage-gated sodium channels. Objectives: This study aimed to form hydroxypropyl methylcellulose (HPMC) extended-release tablets containing OXC combined with vitamin D. Methods: These formulated tablets were tested for their dissolution rate, tablet hardness, friability, thickness and pharmacokinetic parameters (Cmax and Cmin). Blood sodium levels were additionally investigated to ensure the absence of hyponatremia; the main side effect of long-term use of CBZ and some of its derivatives. Results: The use of HPMC inhibited the formation of dihydrate OXC form thus offering a significant extended-release profile. OXC also showed a highlighted capability to attain high bioavailability. Microcrystalline cellulose (MCC) was also added to tablets formed to inhibit polymorphic transformation. Tablets containing OXC co-delivered with vitamin D ensured significantly decreased susceptibility to hyponatremia, and an extended-release profile was evident. Lower amounts of OXC were loaded in formed tablets containing vitamin D owing to the synergistic effect between vitamin D and antiepileptic drugs. Conclusion: Conclusively, employing these newly HPMC-constructed tablets of OXC co-delivered with vitamin D appeared to be a promising option for the effective management of epilepsy with least side effects.

Fabrication and optimization of extended-release beads of diclofenac sodium based on Ca++ cross-linked Taro (Colocasia esculenta) stolon polysaccharide and pectin by quality-by-design approach

The present investigation was aimed to fabricate and optimize extended-release beads of diclofenac sodium based on an ion-cross-linked matrix of pectin (PTN) and taro (Colocasia esculenta) stolon polysaccharide (TSP) with 23 full factorial design. Total polysaccharide concentration (TPC), polysaccharide ratio (PR), and cross-linker concentration ([CaCl2]) were taken as independent factors with two levels of each. Initially, TSP was extracted, purified, and characterized. Fourier-transform infrared spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC) showed drug-polymer compatibility. The study also revealed the significant positive effect of TSP on drug entrapment efficiency (DEE) and sustaining drug release. The response variables (DEE, cumulative % drug-release at 1, 2, 4, 6, and 10 h, release-constant, time for 50 % and 90 % drug release (T50%, T90%), release-similarity factor (f2), and difference factor (f1) were analyzed, and subsequently, independent fabrication variables were numerically optimized by Design-Expert software (Version-13; Stat-Ease Inc., Minneapolis). The optimized batch exhibited appreciable DEE of 88.5 % (± 2.2) and an extended-release profile with significantly higher T50%, T90%, and release-similarity factor (f2) of 4.7 h, 11.4 h, and 71.6, respectively. Therefore, the study exhibited successful incorporation of the novel TSP as a potential alternative adjunct polysaccharide in the pectin-based ion-cross-linked inter-penetrating polymeric network for extended drug release.

Quality by design approach for fabrication of extended-release buccal films for xerostomia employing hot-melt extrusion technology

The study endeavors the fabrication of extended-release adipic acid (APA) buccal films employing a quality by design (QbD) approach. The films intended for the treatment of xerostomia were developed utilizing hot-melt extrusion technology. The patient-centered quality target product profile was created, and the critical quality attributes were identified accordingly. Three early-stage formulation development trials, complemented by risk assessment aligned the formulation and process parameters with the product quality standards. Employing a D-optimal mixture design, the formulations were systematically optimized by evaluating three formulation variables: amount of the release-controlling polymer Eudragit® (E RSPO), bioadhesive agent Carbopol® (CBP 971P), and pore forming agent polyethylene glycol (PEG 1500) as independent variables, and % APA release in 1, 4 and 8 h as responses. Using design of experiment software (Design-Expert®), a total of 16 experimental runs were computed and extruded using a Thermofisher ScientificTM twin screw extruder. All films exhibited acceptable content uniformity and extended-release profiles with the potential for releasing APA for at least 8 h. Films containing 30% E RSPO, 10% CBP 971P, and 20% PEG 1500 released 88.6% APA in 8 h. Increasing the CBP concentration enhanced adhesiveness and swelling capacities while decreasing E RSPO concentration yielded films with higher mechanical strength. The release kinetics fitted well into Higuchi and Krosmeyer-Peppas models indicating a Fickian diffusion release mechanism.

Novel Dry Hyaluronic Acid-Vancomycin Complex Powder for Inhalation, Useful in Pulmonary Infections Associated with Cystic Fibrosis.

Polyelectrolyte-drug complexes are interesting alternatives to improve unfavorable drug properties. Vancomycin (VAN) is an antimicrobial used in the treatment of methicillin-resistant Staphylococcus aureus pulmonary infections in patients with cystic fibrosis. It is generally administered intravenously with a high incidence of adverse side effects, which could be reduced by intrapulmonary administration. Currently, there are no commercially available inhalable formulations containing VAN. Thus, the present work focuses on the preparation and characterization of an ionic complex between hyaluronic acid (HA) and VAN with potential use in inhalable formulations. A particulate-solid HA-VAN25 complex was obtained by spray drying from an aqueous dispersion. FTIR spectroscopy and thermal analysis confirmed the ionic interaction between HA and VAN, while an amorphous diffraction pattern was observed by X-ray. The powder density, geometric size and morphology showed the suitable aerosolization and aerodynamic performance of the powder, indicating its capability of reaching the deep lung. An in vitro extended-release profile of VAN from the complex was obtained, exceeding 24 h. Microbiological assays against methicillin-resistant and -sensitive reference strains of Staphylococcus aureus showed that VAN preserves its antibacterial efficacy. In conclusion, HA-VAN25 exhibited interesting properties for the development of inhalable formulations with potential efficacy and safety advantages over conventional treatment.

Formulation Development of Solid Self-Nanoemulsifying Drug Delivery Systems of Quetiapine Fumarate via Hot-Melt Extrusion Technology: Optimization Using Central Composite Design.

Quetiapine fumarate (QTF) was approved for the treatment of schizophrenia and acute manic episodes. QTF can also be used as an adjunctive treatment for major depressive disorders. QTF oral bioavailability is limited due to its poor aqueous solubility and pre-systemic metabolism. The objective of the current investigation was the formulation development and manufacturing of solid self-nanoemulsifying drug delivery system (S-SNEDDS) formulation through a single-step continuous hot-melt extrusion (HME) process to address these drawbacks. In this study, Capmul® MCM, Gelucire® 48/16, and propylene glycol were selected as oil, surfactant, and co-surfactant, respectively, for the preparation of S-SNEDDS. Soluplus® and Klucel™ EF (1:1) were selected as the solid carrier. Response surface methodology in the form of central composite design (CCD) was utilized in the current experimental design to develop the S-SNEDDS formulations via a continuous HME technology. The developed formulations were evaluated for self-emulsifying properties, particle size distribution, thermal behavior, crystallinity, morphology, physicochemical incompatibility, accelerated stability, and in vitro drug release studies. The globule size and emulsification time of the optimized SNEDDS formulation was 92.27 ± 3.4 nm and 3.4 ± 3.38 min. The differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) studies revealed the amorphous nature of the drug within the formulation. There were no drug-excipient incompatibilities observed following the Fourier transform infrared (FTIR) spectroscopy. The optimized formulation showed an extended-release profile for 24 h. The optimized formulation was stable for three months (last time-point tested) at 40 °C/75% RH. Therefore, the developed S-SNEDDS formulation could be an effective oral delivery platform for QTF and could lead to better therapeutic outcomes.

Designing an effective dissolution test for bilayer tablets tailored for optimal melatonin release in sleep disorder management.

This project aims to investigate the release performance of bilayer tablet (BL-Tablet) designed with both fast and slow-release technology, targeting sleep disorders. The tablet incorporates Melatonin, extracts of Eschscholzia californica and Melissa officinalis. In order to validate the effectiveness of the extended-release profile, an advanced dissolution test was herein proposed. This new method utilizes biorelevant intestinal fluid media and incorporates a stomach-to-intestine fluid changing (SIFC) system. To demonstrate the advantages of employing this method for assessing the controlled release profile of active ingredients, the dissolution results were compared with those obtained using the conventional EU Pharmacopoeia approach. Furthermore, the comparative analysis was extended to include a monolayer tablet version (ML-Tablet) lacking the slow-release technology. Technological characterization and bioaccessibility studies, including intestinal permeability test, were conducted as well to assess the pharmacological performance and bioavailability of active ingredients. The dissolution data recovered revealed that the two dissolution methods did not exhibit any significant differences in the release of ML-Tablet's. However, the dissolution profile of the BL-Tablet exhibited notable differences between the two methods particularly when assessing the behavior of the slow-release layer. In this scenario, both methods initially exhibited a similar release pattern within the first approximately 0.5 h, driven by the fast-release layer of the tablet. Following this, distinct gradual and sustained releases were observed, spanning 2.5 h for the EU Pharmacopoeia method and 8 h for the new SIFC-biorelevant dissolution method, respectively. Overall, the novel method demonstrated a substantial improvement compared to conventional EU Pharmacopoeia test in evaluating the performance of a controlled slow-release technology. Remarkably, the prolonged release technology did not have an adverse impact on melatonin intestinal absorption, and, consequently, maintaining its potential bioavailability of around 78%. Concluding, this research provides valuable insights into how the innovative dissolution test can assist formulators in developing controlled release formulations.

Long-Term Insect Repellent Electrospun Microfibers from Recycled Poly(ethylene terephthalate).

In recent years, there has been an increase in the incidence of insect-borne diseases. Topically applied insect repellents are used to prevent these infectious diseases, but concerns of skin permeability and rapid evaporation rates have made way for alternative preventative methods. Encapsulation of insect repellents in polymeric materials allows for nonskin contact methods of repellent delivery with extended-release profiles without the need for reapplication. Poly(ethylene terephthalate) (PET) is widely used in textiles as well as food packaging and other single-use applications. This short product lifespan makes PET a major environmental pollutant; thus, recycling of PET is of great interest and utility. We report on the fabrication and evaluation of recycled PET microfibers containing N,N-diethyl-meta-toluamide (DEET) and picaridin and the first evaluation of dual repellent loading (DEET/picaridin) via electrospinning. The electrospun microfibers displayed a repellent retention up to 97% within the polymer network upon processing. Release profiles were characterized by isothermal thermogravimetric analysis (TGA). Hansen solubility parameters correlated release profiles with the chemical affinity between PET and the repellent substrate. Insect repellency was assessed against live mosquitoes using a novel bioassay method. Repellency was observed to be as high as 100% for over 1 week and 80% for over 3 weeks. Our method allows for long-lasting repellency with the potential for large-scale textile manufacturing.

Development and In Vitro-In Vivo Correlation Evaluation of IMM-H014 Extended-Release Tablets for the Treatment of Fatty Liver Disease.

This study aimed to develop extended-release tablets containing 25 mg IMM-H014, an original drug formulated by a direct powder pressing method based on pharmaceutical-grade hydrophilic matrix polymers such as hydroxypropyl methylcellulose, to establish an in vitro-in vivo correlation (IVIVC) to predict bioavailability. The tablets' mechanical properties and in vitro and in vivo performance were studied. The formulation was optimized using a single-factor experiment and the reproducibility was confirmed. The in vitro dissolution profiles of the tablet were determined in five dissolution media, in which the drug released from the hydrophilic tablets followed the Ritger-Peppas model kinetics in 0.01 N HCl medium for the first 2 h, and in phosphate-buffered saline medium (pH 7.5) for a further 24 h. Accelerated stability studies (40 °C, 75% relative humidity) proved that the optimal formulation was stable for 6 months. The in vivo pharmacokinetics study in beagle dogs showed that compared to the IMM-H014 immediate release preparation, the maximum plasma concentration of the extended-release (ER) preparation was significantly decreased, while the maximum time to peak and mean residence time were significantly prolonged. The relative bioavailability was 97.9% based on the area under curve, indicating that the optimal formulation has an obvious ER profile, and a good IVIVC was established, which could be used to predict in vivo pharmacokinetics based on the formulation composition.

An Intragastric Delivery Device Employing FDM Technology: 3D-Printed Tablet Containing Green Developed Mosapride-Saccharin Co-crystals

Mosapride citrate (MC) is a poorly soluble short half-life drug with more pronounced absorption in the stomach. The present study aimed to incorporate MC co-crystals with enhanced solubility into 3D-printed floating tablets. MC co-crystals were prepared via the green method using Saccharin sod. as a co-former at a (1:1) molar ratio. The prepared co-crystals were assessed for solubility, FTIR, thermal behavior, and SEM. Then, it was incorporated into zero % infill 3D-printed tablets of different configurations at two thickness levels by the FDM printing technique. Printed tablets were evaluated for dimensions, weight deviation, friability, and in vitro floating behavior. Drug release and kinetic of the MC release were also assessed. Solubility study of the co-crystals showed a significant (p value < 0.05) increased solubility over pure MC. FTIR and thermal behavior confirmed hydrogen bonding formation during co-crystallization. The obstructed particles had an erratic protrusion form, similar to a nodule, as illustrated by SEM. The printed tablets showed acceptable physicochemical properties. Tablets floated for about ≥ 12 h without floating lag time. In vitro drug release exhibited variable extended release profiles with different lag times depending on the configuration indicating that the tablet’s wall thickness and surface area were the factors manipulated to control drug release. Kinetic analysis of the release data displayed intermediate kinetics between zero-order and diffusional kinetics. The intragastric extended release profile for MC co-crystals of improved solubility could be successfully, economically, and quickly developed utilizing the 3D printing technique.Graphical

Preparation of chitosan nanoparticles for simultaneous drug delivery of dacarbazine and enoxaparin in melanoma

The aim of this study was to investigate the anti-melanoma and anti-angiogenic effects of enoxaparin surface-coated dacarbazine-loaded chitosan nanoparticles (Enox-Dac-Chi NPs). The prepared Enox-Dac-Chi NPs had a particle size of 367.95 ± 1.84 nm, zeta potential of −7.12 ± 0.25 mV, efficiency of drug loading (DL%) of 73.90 ± 3.84 %, and attached enoxaparin percentage of 98.53 ± 0.96 %. Both drugs had extended-release profiles and approximately 96 % of enoxaparin and 67 % dacarbazine were released within 8 h. The Enox-Dac-Chi NPs with IC50 of 59.60 ± 1.25 μg/ml were the most cytotoxic against melanoma cancer cells compared with chitosan nanoparticles containing only dacarbazine (Dac-Chi NPs) and free dacarbazine. There was no significant difference between the cellular uptake of Chi NPs and enoxaparin coated Chi NPs (Enox-Chi NPs) in B16F10 cells. Enox-Chi NPs with an average anti-angiogenic score of 1.75 ± 0.125 had more anti-angiogenic effect than enoxaparin. The results showed that simultaneous delivery of dacarbazine and enoxaparin by chitosan nanoparticles can enhance the anti-melanoma effect of dacarbazine. Additionally, enoxaparin can prevent the melanoma metastasis by its anti-angiogenic activity. Thus, the designed nanoparticles can be introduced as effective drug delivery vehicles for the treatment and prevention of metastatic melanoma.

Design and optimization of ciprofloxacin hydrochloride biodegradable 3D printed ocular inserts: Full factorial design and in-vitro and ex-vivo evaluations: Part II

Coupling hot-melt extrusion (HME) with fused deposition modeling three-dimensional printing (FDM-3DP) can facilitate the fabrication of tailored, patient-centered, and complex-shaped ocular dosage forms. We fabricated ciprofloxacin HCl ocular inserts by coupling high-throughput, solvent-free, and continuous HME with FDM-3DP. Insert fabrication utilized biocompatible, biodegradable, bioadhesive Klucel™ hydroxypropyl cellulose polymer, subjected to distinct FDM-3DP processing parameters, utilizing a design of experiment approach to achieve a tailored release profile. We determined the drug content, thermal properties, drug-excipient compatibility, surface morphology, in vitro release, antibacterial activity, ex-vivo transcorneal permeation, and stability of inserts. An inverse relationship was noted between insert thickness, infill density, and drug release rate. The optimized design demonstrated an amorphous solid dispersion with an extended-release profile over 24 h, no physical or chemical incompatibility, excellent mucoadhesive strength, smooth surface, lack of bacterial growth (Pseudomonas aeruginosa) in all release samples, and prolonged transcorneal drug flux compared with commercial eye drops and immediate-release inserts. The designed inserts were stable at room temperature considering drug content, thermal behavior, and release profile over three months. Overall, the fabricated insert could reduce administration frequency to once-daily dosing, affording a promising topical delivery platform with prolonged antibacterial activity and superior therapeutic outcomes for managing ocular bacterial infections.

Chitosan-Based Ciprofloxacin Extended Release Systems: Combined Synthetic and Pharmacological (In Vitro and In Vivo) Studies.

Ciprofloxacin is one of the most effective antibiotics, but it is characterized by a range of side effects. Elaboration of drug-releasing systems which allow to diminish toxicity of ciprofloxacin is a challenging task in medicinal chemistry. The current study is focused on development of new ciprofloxacin releasing systems (CRS). We found that ultrasound efficiently promotes N,N'-dicyclohexyl carbodiimide-mediated coupling between COOH and NH2 functionalities in water. This was used for conjugation of ciprofloxacin to chitosan. The obtained ciprofloxacin/chitosan conjugates are capable of forming their self-assembled nanoparticles (SANPs) in aqueous medium. The SANPs can be additionally loaded by ciprofloxacin to form new CRS. The CRS demonstrated high loading and encapsulation efficiency and they are characterized by extended release profile (20 h). The elaborated CRS were tested in vivo in rats. The in vivo antibacterial effect of the CRS exceeded that of the starting ciprofloxacin. Moreover, the in vivo acute and subacute toxicity of the nanoparticles was almost identical to that of the chitosan, which is considered as the non-toxic biopolymer.

Formulation development and in Vitro–Ex vivo characterization of hot-melt extruded ciprofloxacin hydrochloride inserts for ocular applications: Part I

This study developed, optimized, characterized, and evaluated bioadhesive, hot-melt extruded (HME), extended-release ocular inserts containing ciprofloxacin hydrochloride (CIP-HCL) to improve the therapeutic outcomes of ocular bacterial infections. The inserts were fabricated with FDA-approved biocompatible, biodegradable, and bioadhesive polymers that were tuned in different ratios to achieve a sustained release profile. The results revealed an inverse relationship between the Klucel™ hydroxypropyl cellulose (HPC, 140,000 Da) concentration and drug release and extended-release profile over 24 h. The CIP-HCL-HME inserts presented stable drug content, thermal behavior, surface pH, and release profiles over three months of room-temperature storage and demonstrated adequate mucoadhesive strength. SEM micrographs revealed a smooth surface. Bacterial growth was not observed on the samples during the in vitro release experiment (0.5–24 h), indicating that a minimum inhibitory concentration (MIC) of 90 against Pseudomonas aeruginosa was achieved. Ex vivo transcorneal permeation studies using excised rabbit corneas revealed that the prepared ocular inserts prolonged the transcorneal flux of the drug compared to commercial eye drops and immediate-release inserts and could reduce the administration frequency to once daily. Therefore, the inserts could increase patient compliance and exhibited prolonged antibacterial activity and thus could provide better therapeutic outcomes against ocular bacterial infections.

Hot Melt Extrusion Assisted Felodipine Loaded Liquid Crystal Precursor with Enhanced Solubility and Sustained Drug Release Characteristics

Glyceryl monooleate (GMO) forms cubic mesophase upon hydration with sustained drug release characteristics. However its stickiness and stiffness often creates processing challenges for preparation of formulations. Felodipine (FLD), BCS class II molecule was used as model drug. Thus objective of the current work was to increase manufacturing feasibility of GMO using polymer and to enhance the release of felodipine by preparing LC precursors using HME. HPMC E5 polymer was selected for processing of FLD. Batch optimization was done using 23 Factorial design. The prepared batches were characterized for DSC, FTIR, hot stage microscopy (HSM), plane polarized light microscopy (PPL), PXRD and in vitro dissolution studies. The processing of FLD using HME process showed amorphization as revealed by PXRD studies. DSC and HSM studies showed solubilization of FLD in the molten mass of GMO and HPMC E5 confirming formation of solid dispersion. PPL demonstrated formation of cubic LC phase by GMO upon hydration of prepared formulations. The optimized batch of felodipine showed significant improvement in the dissolution profile of FLD with extended release profile. HME assisted liquid crystal precursors could act as promising formulations for BCS II drugs requiring extended drug release profile with improved processing feasibility of GMO.

Biomimetic Targeted Theranostic Nanoparticles for Breast Cancer Treatment.

The development of biomimetic drug delivery systems for biomedical applications has attracted significant research attention. As the use of cell membrane as a surface coating has shown to be a promising platform for several disease treatments. Cell-membrane-coated nanoparticles exhibit enhanced immunocompatibility and prolonged circulation time. Herein, human red blood cell (RBC) membrane-cloaked nanoparticles with enhanced targeting functionality were designed as a targeted nanotheranostic against cancer. Naturally, derived human RBC membrane modified with targeting ligands coated onto polymeric nanoparticle cores containing both chemotherapy and imaging agent. Using epithelial cell adhesion molecule (EpCAM)-positive MCF-7 breast cancer cells as a disease model, the nature-inspired targeted theranostic human red blood cell membrane-coated polymeric nanoparticles (TT-RBC-NPs) platform was capable of not only specifically binding to targeted cancer cells, effectively delivering doxorubicin (DOX), but also visualizing the targeted cancer cells. The TT-RBC-NPs achieved an extended-release profile, with the majority of the drug release occurring within 5 days. The TT-RBC-NPs enabled enhanced cytotoxic efficacy against EpCAM positive MCF-7 breast cancer over the non-targeted NPs. Additionally, fluorescence images of the targeted cancer cells incubated with the TT-RBC-NPs visually indicated the increased cellular uptake of TT-RBC-NPs inside the breast cancer cells. Taken together, this TT-RBC-NP platform sets the foundation for the next-generation stealth theranostic platforms for systemic cargo delivery for treatment and diagnostic of cancer.

Computational Investigation to Design Ofloxacin-Loaded Hybridized Nanocellulose/Lipid Nanogels for Accelerated Skin Repair.

The pharmaceutical application of biomaterials has attained a great success. Rapid wound healing is an important goal for many researchers. Hence, this work deals with the development of nanocellulose crystals/lipid nanogels loaded with ofloxacin (OFX) to promote skin repair while inhibiting bacterial infection. Ofloxacin-loaded hybridized nanocellulose/lipid nanogels (OFX-HNCNs) were prepared and evaluated adopting a computational method based on regression analysis. The optimized nanogels (OFX-HNCN7) showed a spherical outline with an encapsulation efficiency (EE), particle size (PS) and zeta potential (ZP) values of 97.53 ± 1.56%, 200.2 ± 6.74 nm and −26.4 ± 0.50 mV, respectively, with an extended drug release profile. DSC examination of OFX-HNCN7 proved the amorphization of the encapsulated drug into the prepared OFX-HNCNs. Microbiological studies showed the prolonged inhibition of bacterial growth by OFX-HNCN7 compared to the free drug. The cytocompatibility of OFX-HNCN7 was proved by Sulforhodamine B assay. Tissue repair was evaluated using the epidermal scratch assay based on cell migration in human skin fibroblast cell line, and the results depicted that cell treated with OFX-HNCN7 showed a faster and more efficient healing compared to the control. In overall, the obtained findings emphasize the benefits of using the eco-friendly bioactive nanocellulose, hybridized with lipid, to prepare a nanocarrier for skin repair.

Bacteria-mediated metformin-loaded peptide hydrogel reprograms the tumor immune microenvironment in glioblastoma

The tumor immune microenvironment (TIME) is one of the significant hallmarks of cancer and has the important role of largely determining the malignancy level of tumors. As an approach to break through this bottleneck of tumor treatment methods, the TIME can be reprogrammed by certain nanomaterials. Here, we coated C-novyi-spores with melittin-RADA32 nanofiber hybrid peptide and loaded the immunomodulator metformin to obtain MRM-coated spores as a powerful antitumor nanodrug against glioblastoma (GBM), which is based on the activation of the TIME. MRM-coated spores exhibit extended-release profiles and an enhanced killing effect on GBM both in vitro and in vivo. Furthermore, MRM-coated spores can educate the innate and adaptive immune system by inducing sustainable CD8+ T cell responses, promoting M1 macrophage polarization, and regulating the expression of HIF1-α, PDL1, and CXCL9 in TIME. In intracranial applications, MRM-coated spores showed excellent biosafety and a strong therapeutic effect. In summary, peptide hydrogels provide a promising strategy in which advantages of different treatment methods can be incorporated to synthesize potent antitumor drugs with mild side effects from bacteria-mediated nanomaterials.

Hydrogel-forming microarray patches with cyclodextrin drug reservoirs for long-acting delivery of poorly soluble cabotegravir sodium for HIV Pre-Exposure Prophylaxis.

Hydrogel-forming microarray patches (HF-MAPs) offer minimally invasive, pain-free and prolonged drug delivery. These devices are designed to be self-administered and self-disabling, avoiding contaminated sharps waste generation. Cabotegravir sodium (CAB-Na) is a poorly soluble anti- human immunodeficiency virus (HIV) drug for the treatment and pre-exposure prophylaxis of HIV infection that lends itself to depot formation following intradermal delivery but presents significant challenges when delivered via HF-MAPs, whose nature is aqueous. Herein, we have investigated, for the first time, the use of hydroxypropyl-β-cyclodextrin (HP-β-CD) to enhance the solubility of CAB-Na, and its effect on intradermal delivery via HF-MAPs. Accordingly, tablet reservoirs containing CAB-Na and HP-β-CD were formulated. These novel reservoirs were combined with two different HF-MAP formulations (MAP1 (Gantrez S97®+poly (ethylene glycol) 10,000+Na2CO3) and MAP2 (poly (vinyl pyrrolidone) 58kDa+poly (vinyl alcohol) 85-120kDa+citric acid)) to form fully integrated MAP devices which were tested in both ex vivo and in vivo settings. Ex vivo skin deposition results for MAP1 and MAP2 showed that 141±40μg and 342±34μg of CAB-Na was deposited into 0.5cm2 of excised neonatal porcine skin after 24h, respectively. Based on these findings, the in vivo pharmacokinetics of MAP2 were investigated over 28days using a Sprague-Dawley rat model. After 24h patch application, MAP2 demonstrated an extended drug release profile and an observed Cmax of 53.4±10.16μg/mL, superior to that of an FDA-approved CAB-nanosuspension administered via intramuscular application (Cmax of 43.6±5.3μg/mL). Consequently, this tablet integrated MAP device is considered to be a viable option for the intradermal delivery of hydrophobic anti-HIV drugs.

Investigation of poly(2-ethyl-2-oxazoline) as a novel extended release polymer for hot-melt extrusion paired with fused deposition modeling 3D printing

This study investigates the application of poly (2-ethyl-2-oxazoline) (PEtOx) as the main matrix for the development of solid oral tablets with extended release profile using hot-melt extrusion (HME) coupled with fused deposition modeling (FDM) three-dimensional (3D) printing techniques. Acetaminophen (APAP) was used as the model drug. Different grades of PEtOx and the polymers poly (ethylene oxide) (PEO) and Eudragit® RL PO (ERL) were used to formulate the tablets. Printability was evaluated by three-point bend tests, and scanning electron microscopy was used to assess the surface morphology of the tablets. The crystalline state of the drug was evaluated using differential scanning calorimetry. In vitro dissolution studies showed that the 3D-printed tablets exhibited the desired extended release profiles. The PEtOx and ERL combined formulation exhibited slower drug release than the PEtOx and PEO combined formulation. The infill densities of the tablets and the molecular weights of the PEtOx polymer both impacted the drug release rate. Overall, PEtOx-based solid oral tablets were successfully produced via HME coupled FDM 3D printing technique. This study supports the potential of developing PEtOx-based tablets for extended release drug delivery to improve individualized drug administration.