Conventional Formulation Research Articles

Formulation, Development and Evaluation of Pulsatile Tablets of Etoricoxib

Aim: This research aimed to develop a pulsatile drug delivery system (PDDS) for etoricoxib, selective COX-2 inhibitor analgesic, to address the limitations of conventional formulations by releasing the drug at specific intervals aligned with the circadian rhythm of pain. Method: Core tablets containing Etoricoxib were prepared by direct compression with varied concentrations of croscarmellose sodium as a superdisintegrant. The optimized core tablets were coated using hydrophilic (HPMC K4M) and hydrophobic (ethyl cellulose) polymers in different ratios to create press-coated pulsatile tablets with varying lag times. Physical properties hardness, thickness, friability, and disintegration, drug content uniformity, and in vitro release were evaluated. Results: The core tablets exhibited rapid drug release, with batch C3 showing 98.61% release within 60 minutes. Press-coated formulations with different polymer ratios exhibited varying lag times, with batch F3 achieving the optimal balance—providing a 4-hour lag time and 96.6% drug release over 8 hours. Stability studies confirmed the physical and chemical stability of the optimized formulation (F3) over 6 months under accelerated conditions. Conclusion: The developed press-coated pulsatile tablets of etoricoxib successfully achieved a controlled lag time and sustained drug release profile, making them suitable for chronopharmacological management of pain. Keywords: Etoricoxib, Pulsatile Drug Delivery System, Chronopharmacology, Press-Coated Tablets. etc

In vitro evaluation of lipidic nanocarriers for mebendazole delivery to improve anticancer activity

Objective Enhance the anticancer activity of the repurposed drug Mebendazole (MBZ) against A549 cell lines by developing nanostructured lipid carriers (NLCs). Significance MBZ, an anthelmintic drug, exhibits anticancer properties primarily through the inhibition of Ran GTPase and mitotic spindle assembly. Enhancing its delivery and efficacy via NLC could provide a novel and effective approach for lung cancer treatment. Methods NLCs were prepared by mixing different ratios of solid lipid (Stearic acid) and liquid lipid (Oleic acid) with surfactants and emulsifiers. The NLCs were fully characterized to ensure stability, particle size, zeta potential, and encapsulation efficiency (EE%). The stability of the NLCs was monitored over a 3-week period. The anticancer activity of MBZ-NLCs was evaluated using IC50 assays and in vitro scratch assays. Results The NLCs exhibited an average particle size of 300 ± 10 nm and a zeta potential of -27 ± 0.5 mV, indicating good stability. EE% significantly improved from 40% in conventional liposome formulations to 90.7% in NLCs. The anticancer activity of MBZ-NLCs was markedly enhanced, with an IC50 of 62 nM compared to 581 nM for free MBZ, representing a 10-fold increase in potency. Additionally, in vitro scratch assays revealed that MBZ-NLCs effectively prevented cell-cell contact, further supporting their potential for improved therapeutic efficacy. Conclusions MBZ-NLCs exhibit significantly improved stability, encapsulation efficiency, and anticancer activity compared to free MBZ. These promising results suggest that MBZ-NLCs could be a potent therapeutic approach for lung cancer treatment, warranting further in vivo studies and exploration of different administration routes.

Nourishing Aquatic Life: A Comprehensive Reviewing of Fish Feed Strategies and Disease Combat in Aquaculture

With an increasing focus on creating sustainable methods that satisfy the nutritional requirements of aquatic life while successfully containing disease outbreaks, aquaculture has emerged as a crucial element of global food security. Nourishing Aquatic Life: A Comprehensive Review of Fish Feed Strategies and Disease Combat in Aquaculture explores the delicate balance between disease management and feed optimization, two crucial factors influencing the ecological sustainability and productivity of aquaculture systems. Innovative substitutes, including plant-based proteins, insect meal, and microbial sources, are being assessed alongside conventional fish feed formulations, which rely on fishmeal and fish oil to lessen environmental stresses while preserving high nutritional value. This article also covers how probiotics, prebiotics, and immunostimulants can improve fish immunity and resilience against common diseases, lowering the need for antibiotics and the likelihood of resistance. Additionally, we look at the most recent developments in fish feed formulation using biofloc, genetic engineering, and nanotechnology, emphasizing their implications for better fish health and disease resistance. These innovative strategies offer a hopeful vision for the future of aquaculture, inspiring us to continue our efforts in this field.

Comparative bioavailability study of supplemental oral Sucrosomial® vs. oral conventional vitamin B12 in enhancing circulatory B12 levels in healthy deficient adults: a multicentre, double-blind randomized clinical trial

BackgroundVitamin B12 is essential for neurological function, red blood cell formation, and DNA synthesis. Deficiency can lead to diverse health conditions, including megaloblastic anemia and neurological issues. Oral supplementation is a standard treatment for B12 deficiency. The Sucrosomial® carrier system offers an innovative approach that enhances supplemental nutrient absorption and bioavailability.ObjectivesThis study aimed to compare the effectiveness of oral Sucrosomial® vitamin B12 formulation vs various conventional B12 supplements, randomly selected from local pharmacies, in increasing and maintaining circulatory B12 levels in healthy deficient adults (200–300 pg/mL).MethodsA randomized, double-blind clinical trial was conducted across three centers in Pakistan from April to July 2024. At KEMU, participants received either Sucrosomial® vitamin B12 or Mecogen SL B12; at LRH, Sucrosomial® B12 or B-SUB B12; and at LUMHS, Sucrosomial® B12, Evermin B12, or Neuromax B12. Participants took a daily single dose of 1,000 μg of the assigned B12 formulation for 7 days. Serum B12 levels were measured at baseline (day 0) and on days 1, 3, 5, and 7.ResultsSucrosomial® B12 was significantly more effective than conventional B12 formulations in increasing and maintaining higher serum B12 levels across all time points. At KEMU, it reached a peak concentration of 454 ± 3.9 pg/mL by day 5, compared to 274 ± 11.1 pg/mL with Mecogen SL B12. At LRH, it peaked at 496 ± 34.4 pg/mL by day 5 versus 304 ± 49.4 pg/mL for B-SUB B12. At LUMHS, it reached 592.7 ± 74.3 pg/mL by day 7, compared to 407.24 ± 41.6 pg/mL for Evermin B12 and 263.82 ± 23.8 pg/mL for Neuromax B12. Sucrosomial® B12 was the only formulation to surpass the deficiency-borderline threshold (200–300 pg/mL) within 24 h of the first dose and was well tolerated with no reported side effects.ConclusionSucrosomial® vitamin B12 demonstrated superior efficacy in rapidly and consistently elevating and maintaining higher circulatory B12 levels compared to conventional supplements. Its characteristic absorption mode and proven efficacy suggest it could effectively address B12 deficiency in a broad range of populations, including those with gastrointestinal conditions and pernicious anemia, thereby supporting overall health.Clinical trial registrationclinicaltrials.gov, NCT06376591.

Effect of nanoformulated cypermethrin, a parasiticide in Labeo rohita fingerlings: impact on biochemical, haematological, and stress response.

Cypermethrin is a pyrethroid insecticide used in aquaculture farms against ectoparasites. The conventional pesticide formulations are now being found to be greatly ineffective at low dosages, and their indiscriminate usage may cause undesired effects in ecosystems. So, the current study was designed to develop a nanoformulation of cypermethrin that would have many advantages over conventional pesticide formulations, and the toxic effects of this formulation were then tested on the carp Labeo rohita fingerlings. The 96-h LC50 was estimated at 0.018mg L-1 after the acute toxicity study. Chronic toxicity studies were carried out, exposing the fish to two sublethal doses via 1/10th (C1) and 1/50th (C2) of 96-h LC50 for a period of 45days. The nanoformulation exposure caused a significant reduction in the brain AChE enzyme activity. Catalase and glutathione-s-transferase enzyme activity in the gills and liver increased significantly, as did superoxide dismutase enzyme activity in the kidney. Serum total protein, triglycerides, cholesterol, and some serum enzyme activities decreased. In contrast, white blood cells, red blood cells, haemoglobin, and hematocrit levels decreased only in fish exposed to a higher dose. As baseline information, these findings may aid in understanding the toxic effect of nanoformulated cypermethrin on finfish.

Antifeedant Nanosuspension Formula of <i>Tithonia diversifolia</i> Leaf Extract by Emulsion Inverse Method to Control <i>Crocidolomia pavonana</i> Cabbage Pest Insect

The leaf extract from Tithonia diversifolia is recognized for its ability to deter feeding in various Lepidoptera insect pests, including the larvae of Crocidolomia pavonana. Presently, transformation efforts from conventional formulations into nano-based formulations for biopesticides exhibit enhanced effectiveness and efficiency. Utilizing a low-energy process, an inversion emulsion facilitates the dispersion of the extract suspension in an organic solvent into a water-immiscible solvent using a suitable surfactant. The forming nano-size droplets in water (t1, t2, t3, t4) are influenced by the ratio of surfactant and organic suspension (Water: Tween 80: Organic suspension). The emulsification method successfully formulated T. diversifolia leaf extract, into dispersed nano-size and submicron suspensions in water. The t3 formula exhibits the smallest nano-size dispersed in water (D=23.6 ± 39.6 nm; polydispersity index IP=0.702) and enhanced wettability, evident in the lower contact angle of the droplet on the cabbage leaf surface (49.4°) compare with the control group. The Phytochemicals confirmed by IR-spectra analysis identified the phenols, alkaloids, and steroids constituents of leaf extract, which are known to have antifeedant properties. The enhanced antifeedant properties of T. diversifolia nanosuspension against C. pavonana third-instar larvae demonstrated by the antifeedant test results showing that t3 is the most successful deterrent larvae feeding activity compared to the control (P<0.05), due to the highest total antifeedant coefficient (74.27%) in a category medium antifeedant activity, while the non-emulsification displayed the lowest antifeedant coefficient (25.36%) in a category as low antifeedant activity. T. diversifolia leaf extract with a nano-based formula succeeded resulting in dispersed nano-size and submicron suspension in aqueous media, thereby reducing surface tension and enhancing wettability on the leaf surface during application. The improved dispersion of antifeedant nanosuspension on the leaf surface results in more effective delivery to target insects.

DEVELOPMENT AND EVALUATION OF CYCLODEXTRIN NANOSPONGES-BASED TOPICAL FORMULATION OF TAZAROTENE

Objective: Tazarotene is used as a topical retinoid for the treatment of acne, psoriasis and sun-damaged skin. But its topical formulation has many side effects, including itching, burning, dryness, redness, stinging, rash blistering, skin discoloration, peeling at the site of application and low bioavailability. The present study focuses on the reduction of side effects and enhancement of solubility and topical bioavailability of tazarotene by using cyclodextrin-based nanosponges. Methods: Nanosponge of tazarotene were prepared by lyophilization method. The physiochemical characterization of plain nanosponges and drug-loaded nanosponges were performed using Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and X-ray Diffractometer (XRD) studies. The drug-loaded nanosponges were incorporated into a carpool-based gel formulation. The prepared formulation was evaluated for viscosity, dissolution and stability. FTIR, DSC and XRD studies confirmed the formation of inclusion complex of tazarotene with nanosponges. Results: The particle size of the drug-loaded nanosponges was found to be in the range of 156.72 to 163.48 nm. Transmission Electron Microscopy (TEM) images revealed the regular spherical shape of both the nanosponges that are unaffected even after drug encapsulation. The pH of the gel formulations was found to be in the range of 5.86 to 6.46. The gel formulation resulted in the diffusion of drug in controlled manner for up to 24 h. The in vitro dissolution studies revealed that nanosponges-based topical formulation had better results than the marketed product. Conclusion: Thus, the study showed that nanosponge-based gel formulation can be a possible alternative to conventional formulations of tazarotene with enhanced bioavailability and skin retention characteristics for topical application.

Vali@mPEG‐TK‐COS: A Dual‐Function Nano‐Pesticide for Fungicidal Action and Plant Immune Modulation

ABSTRACTPesticides play a crucial role in safeguarding crops against pathogens and pests, yet the limited bioavailability of conventional formulations leads to excessive usage, causing environmental and health concerns. In this study, we developed a novel intelligent response‐controlled release nano‐pesticide, Vali@mPEG‐TK‐COS, by coupling chitosan oligosaccharide (COS), a plant immunity regulator, and methoxy polyethylene glycols (mPEG) at either end of thioketal (TK), a material responsive to reactive oxygen species (ROS), and incorporating validamycin (Vali) for controlled release. Vali@mPEG‐TK‐COS exhibits ROS‐responsive behaviour, releasing Vali and COS in response to plant ROS bursts, exhibiting dual capabilities in pathogen control and plant immunity induction during pathogenic attacks. Plant disease experiments confirmed the superior efficacy of Vali@mPEG‐TK‐COS against Rhizoctonia solani, surpassing the control effects of Vali or COS alone. This study presents a sophisticated ROS‐responsive controlled‐release nano‐pesticide with dual fungicidal and plant immunomodulatory properties, offering an advanced strategy to enhance the efficiency of existing pesticides and promote sustainable crop production by reducing overall pesticide usage.

Modifications of SPH towards three-dimensional simulations of an icy moon with internal ocean

There are some traces of the existence of internal ocean in some icy moons, such as the vapor plumes of Europa and Enceladus. This implies a region of liquid water beneath the surface ice shell. Since liquid water would be essential for the origin of life, it is important to understand the development of these internal oceans, particularly their temperature distribution and evolution. The balance between tidal heating and radiative cooling is believed to sustain liquid water beneath an icy moon’s surface. We aim to simulate the tidal heating of an internal ocean in an icy moon using 3-dimensional numerical fluid calculations with the Smoothed Particle Hydrodynamics (SPH) method. We incorporated viscosity and thermal conduction terms into the governing equations of SPH. However, we encountered two issues while calculating rigid body rotation using SPH with a viscous term: (1) conventional viscosity formulations generated unphysical forces that hindered rotation, and (2) there was artificial internal energy partitioning within the layered structure, which was due to the standard SPH formulations. To address the first issue, we modified the viscosity formulation. For the second, we adopted Density Independent SPH (DISPH) developed in previous studies to improve behavior at discontinuous surfaces. Additionally, we implemented radiative cooling using an algorithm to define fluid surfaces via the particle method. We also introduced an equation of state accounting for phase transitions. With these modifications, we have refined the SPH method to encompass all necessary physical processes for simulating the evolution of icy moons with internal oceans.

Enhancement of oral bioavailability of celastrol by chitosan microencapsulated porous starch carriers

Celastrol demonstrates significant potential in immunomodulatory applications; however, its low oral bioavailability presents a substantial obstacle to its clinical translation. Here, we combined porous starch with chitosan to develop an efficacious microencapsulation system aimed at enhancing the oral absorption of celastrol. Microcapsule carrier for celastrol was formulated Through the utilization of chitosan-coated porous starch particle technology and Subsequent evaluations of the morphology and release kinetics of microcapsules. The impact of microencapsulation on the enhanced absorption of celastrol was assessed through Caco-2 cell uptake experiments and in vivo pharmacokinetic studies. FT-IR analysis revealed the stable presence of celastrol in an amorphous state within the microcapsules, facilitated by hydrogen-bonding interactions between celastrol and porous starch. Simulated release experiments indicated that the chitosan coating improved the stability and extended the release of celastrol. Cell experiments, as well as in vivo distribution and pharmacokinetic investigations, demonstrated that the chitosan microencapsulation strategy significantly enhanced cellular uptake and in vivo absorption of celastrol, resulting in notably higher bioavailability compared to conventional formulations. This study successfully demonstrated the remarkable efficacy of chitosan microencapsulated porous starch carriers in enhancing the oral bioavailability of celastrol, revealing novel potential applications for these two food-grade materials in delivery systems.

Glycerol-silica/chitosan conjugated self-assembled nano-flower framework for Herstulla thompsoni delivery with effectiveness in natural settings: Optimization and pilot scale production

Hirsutulla thompsoni (HTS) is an entomopathogenic fungus (EPF), a secure and efficient substitute for synthetic insecticides. However, its susceptibility to degradation in conventional formulations limits its practical use for agricultural practices. In light of current setbacks, this work proposes using a glycerol-silica/chitosan nanoflower gel (NFG) as an efficient delivery system to enhance the efficacy of HTS. Inspired by glycerol-silica-chitosan conjugation, NFG self-assembles into flowers. The HTS-loaded nanoflower gel (HTS_NFG) features a flower-shaped morphology, an average size of 232 nm, and a zeta potential of +31.84mv. The laboratory-scale NFG is optimized with ingredients and process factors using multivariate principal component analysis (PCA), which progressed to pilot size 10 kg/shift. The notable foliage retention attributable to chitosan and lower contact angle was achievable on the hydrophobic leaf surface. The result of foliage retention and contact angle obtained showed a significant effect of NFG (p < 0.05). HTS_NFG was comparatively safer towards Chlorella spp. algae and Artemia salina, significant from other treatments (p < 0.05). Field efficacy evaluation demonstrated that the NFG was as effective as the reference sample against aphids. With its proven effectiveness, the NFG may be an aesthetic, sustainable, and feasible alternative for agro-production.

Chitin nanocrystal Pickering emulsions for sustainable release pesticide microencapsulation with superior leaf adhesion and enhanced safety

Traditional pesticides often exhibit high non-target toxicity, poor stability, short persistence, and susceptibility to wash-off by rain. Pesticide microencapsulation represents a significant advancement in formulation strategies, addressing safety and sustainability concerns associated with conventional pesticides. This study explores the utilization of biodegradable chitin nanocrystals (ChNCs), prepared via acid hydrolysis, for the development of pesticide microcapsules. Specifically, ChNCs were employed to emulsify molten pesticides, followed by interfacial polymerization to fabricate pesticide-loaded microcapsules. Using molten emulsification and Pickering emulsion templates offer a simple and solvent-free approach for microcapsule preparation, eliminating the need for conventional surfactants. The microcapsules displayed a size distribution ranging from hundreds of nanometers to several micrometers, which could be tuned by adjusting the ChNCs content. These microcapsules demonstrated remarkable properties, including a high pesticide loading capacity (reaching 78.7% for lambda-cyhalothrin), excellent storage stability, and enzyme-responsive release behavior. Furthermore, the abundant positive charges enhanced the interaction between the microcapsules and leaf surfaces, leading to improved pesticide retention. Microencapsulation reduces acute insecticidal activity of pesticides due to the slow-release effect; however, field experiments provide compelling evidence that microcapsule formulations significantly prolong pesticide efficacy compared to conventional formulations. Additionally, microencapsulation significantly improved the safety of pesticides, with the LC50 increasing from 0.0116 mg/L to 3.75 mg/L. Overall, this study introduces a promising method for pesticide microencapsulation using ChNCs Pickering emulsion, highlighting its potential advantages and providing valuable insights for the development of environmentally friendly and novel pesticide formulations.

Optimization of Glibenclamide Loaded Thermoresponsive SNEDDS Using Design of Experiment Approach: Paving the Way to Enhance Pharmaceutical Applicability.

Thermoresponsive self-nanoemulsifying drug delivery systems (T-SNEDDS) offer a promising solution to the limitations of conventional SNEDDS formulations. Liquid SNEDDS are expected to enhance drug solubility; however, they are susceptible to leakage during storage. Even though solid SNEDDS offers a solution to this storage instability, they introduce new challenges, namely increased total dosage and potential for drug trapping within the formulation. The invented T-SNEDDS was used to overcome these limitations and improve the dissolution of glibenclamide (GBC). Solubility and transmittance studies were performed to select a suitable oil and surfactant. Design of Experiments (DoE) software was used to study the impact of propylene glycol and Poloxamer 188 concentrations on measured responses (liquefying temperature, liquefying time, and GBC solubility). The optimized formulation was subjected to an in vitro dissolution study. The optimized T-SNEDDS consisted of Kolliphor EL and Imwitor 308 as surfactants and oil. The optimized propylene glycol and Poloxamer 188 concentrations were 13.7 and 7.9% w/w, respectively. It exhibited a liquefying temperature of 35.0 °C, a liquefying time of 119 s, and a GBC solubility of 5.51 mg/g. In vitro dissolution study showed that optimized T-SNEDDS exhibited 98.8% dissolution efficiency compared with 2.5% for raw drugs. This study presents a promising approach to enhance pharmaceutical applicability by resolving the limitations of traditional SNEDDS.

Synergetic Hybridization Strategy to Enhance the Dynamicity of Poorly Dynamic CO2‐derived Vitrimers achieved by a Simple Copolymerization Approach

AbstractCopolymerization allows tuning polymer's properties and a synergetic effect may be achieved for the resulting hybrid, i.e., outperforming the properties of its parents as often observed in natural materials. This synergetic concept is herein applied to enhance both dynamicity and properties of vitrimeric materials using poorly dynamic hydroxyurethane and non‐dynamic epoxy thermosets. The latter generates activated hydroxyl, promoting exchange reactions 15 times faster than pure polyhydroxyurethanes. This strategy allows obtaining catalyst‐free high‐performance vitrimers from conventional epoxy‐amine formulations and an easily scalable (bio‐)CO2‐based yet poorly efficient dynamic network. The resulting hybrid network exhibits modulus retention superior to 95% with fast relaxation (&lt;10 min). The hydroxyurethane moieties actively participate in the network to enhance the properties of the hybrid. The material can be manufactured as any conventional epoxy formulation. This new strategy to design dynamic networks opens the door to large‐scale circular high‐performance structural carbon fiber composites (CFRP). The CFRP can be easily reshaped and welded from flat plates to complex geometries. The network is degradable under mild conditions, facilitating the recovery and re‐use of high‐added‐value fibers. This accessible and cost‐effective approach provides a versatile range of tunable dynamic epoxides, applicable across various industries with minimal adjustments to existing marketed products.

Facial Amphiphile-Modified Lipids Highly Sensitize Liposomes toward Secretory Phospholipase A2.

Upregulated secretory phospholipase A2 (sPLA2) in tumors has been proposed as a stimulus to trigger drug release from liposomes for therapeutic effects. However, the current strategy for developing sPLA2-responsive liposomes merely considering substrate preference suffers from limited membrane disruptive effects induced by enzymatic hydrolysis and safety issues resulting from the overuse of sPLA2-preferred lipids. Here, a membrane-destabilizing mechanism based on enzymatic extraction and the transition of facial amphiphiles (FAs) within lipid membranes was introduced. Enzymatic degradation of FA-modified lipids, a process involving substrate extraction of lipids from membranes and cleavage of sn-2 ester bonds by sPLA2, rotation, and interface settling of detached FAs, caused tremendous efflux of payloads from liposomes, termed the SECRIS effect. In the presence of sPLA2, oxaliplatin (L-OHP) loaded liposomes containing FA-modified lipids showed enhanced drug release, comparable in vitro cytotoxicity, and excellent in vivo antitumor efficacy and reduced adverse syndromes in Colo205-bearing mice compared to conventional sPLA2-labile formulations. The discovery of the SECRIS effect creates a new pathway to engineer liposome platforms for the treatment of sPLA2-positive tumors.

Vinyl methyl oxazolidinone and dimethyl itaconate as styrene substitutes for conventional high‐temperature unsaturated polyester resins

AbstractStyrene substitution is a major area of interest in the unsaturated polyester resins (UPR) industry and research. For most styrene‐free UPRs the unsaturated polyester (UP) formulation was tailored for less toxic reactive diluent monomers (RDM). The main challenge is finding a RDM that can directly substitute styrene in industrial UPR formulations without deterioration of resin and thermoset properties. Therefore, this study concerns vinyl methyl oxazolidinone (VMOX®) as a reactive diluent monomer for industrial high‐temperature UPRs. VMOX® and styrene were compared with dimethyl itaconate (DMI), methyl methacrylate, 2‐hydroxyethyl methacrylate, isobornyl methacrylate, triethylene glycol dimethacrylate and 1,4‐butanediol dimethacrylate. Further, the properties of produced resins and thermosets were investigated. The most striking result was comparable glass transition temperature, crosslink density, and residual monomer content of VMOX®‐ and styrene‐based thermosets. Subsequently, DMI was applied as a reactive co‐diluent for VMOX®‐based resins and thermosets. Significant improvement of VMOX® conversion during resin curing was observed. In conclusion, VMOX® is an excellent candidate for direct styrene substitution in industrial high‐temperature UPRs. Furthermore, the application of DMI as a reactive co‐diluent improves the reactivity of VMOX®‐based resins. The application of VMOX® and reactive co‐diluent monomer certainly creates new possibilities for direct styrene substitution in conventional UPR formulations.

Oligonucleotide-Linked Lipid Nanoparticles as a Versatile mRNA Nanovaccine Platform.

An effective delivery platform is crucial for the development of mRNA vaccines and therapeutics. Here, a versatile platform utilizing cholesterol-modified oligonucleotides (L-oligo) that bind to the mRNA within lipid nanoparticles (LNP), and enables the effective delivery of the mRNA into target cells is introduced. mRNA incorporated into LNPs via linkage with L-oligo, termed oligonucleotide-linked LNP (lnLNP), is superior in cellular uptake and transfection efficiency in target cells in vitro and in vivo, compared to the conventional LNP formulations. It is further applied lnLNP as an mRNA vaccine platform for SARS-CoV-2, demonstrating robust induction of neutralizing activity as well as polyfunctional SARS-CoV-2-specific T-cell response in vivo. The current strategy can be versatilely applied to different LNP platforms, for vaccine and therapeutic applications against various diseases, such as infections and cancers.

Using the refined Developability Classification System (rDCS) to guide the design of oral formulations

The refined Developability Classification System (rDCS) provides a comprehensive animal-free approach for assessing biopharmaceutical risks associated with developing oral formulations. This work demonstrates practical application of a recently advanced rDCS framework guiding formulation design for six diverse active pharmaceutical ingredients (APIs) and compares rDCS classifications with those of the Biopharmaceutics Classification System (BCS). While the BCS assigns five of the APIs to class II/IV, indicating potentially unfavorable biopharmaceutical attributes, the rDCS provides a more nuanced risk assessment. Both BCS and rDCS assign acetaminophen to class I at therapeutic doses. Voriconazole and lemborexant (both BCS II) are classified in rDCS class I at therapeutic doses, indicating suitability for development as conventional oral formulations. Fedratinib is classified as BCS IV but the rDCS indicates a stratified risk (class I, IIa or IIb), depending on the relevance of supersaturation/precipitation in vivo. Voxelotor and istradefylline (both BCS II) belong to rDCS class IIb, requiring solubility enhancement to achieve adequate oral bioavailability. Comparing the rDCS analysis with literature on development and pharmacokinetics demonstrates that the rDCS reliably supports oral formulation design over a wide range of API characteristics, thus providing a strong foundation for guiding development.

Preservative-free electrospun nanofibrous inserts for sustained delivery of ceftazidime; design, characterization and pharmacokinetic investigation in rabbit's eye

Ocular drug delivery presents significant challenges, attributed to the various anatomical and physiological barriers, as well as the limitations associated with conventional ocular formulations including low bioavailability, necessitating frequent dosing. The objective of the essay was to design sustained release nanofibrous inserts loaded with ceftazidime (CAZ), an antibiotic effective against gram-negative and gram-positive microorganisms, for the treatment of ocular infections. These nanofibers were fabricated using the electrospinning technique, employing biodegradable polymers such as polyvinyl alcohol (PVA), polycaprolactone (PCL) and Eudragit® (EUD). The nanofibrous inserts exhibited adequate mechanical strength for ocular use with an average diameter < 250 nm. In the initial 12-h period, a burst drug release was observed, followed by a controlled release for 120 h. Cell viability test confirmed the non-toxicity and safety of the nanofibers. The in vivo study demonstrated that the inserts sustain a drug concentration exceeding the minimum inhibitory concentration (MIC) of Pseudomonas aeruginosa and Staphylococcus aureus for 4 and 5 days, respectively. The AUC0–120 for CAZ-PVA-PCL was reported 11,882.81 ± 80.5 μg·h/mL and for CAZ-PVA-EUD was 9649.39 ± 86.84 μg·h/mL. The nanofibrous inserts' extended drug release maintains effective antimicrobial concentrations, avoids the fluctuations of eye drops, and, by being preservative-free, eliminates cytotoxicity.

Formulation optimization of chitosan surface coated solid lipid nanoparticles of griseofulvin: A Box-Behnken design and in vivo pharmacokinetic study.

Solid lipid nanoparticles (SLNs) are becoming increasingly favored for their robust biocompatibility and their capacity to enhance drug solubility, particularly for drugs with limited water solubility. This study delves into the effectiveness of the hot melt sonication technique in fabricating SLNs with high drug loading capabilities and sustained release characteristics. Griseofulvin (GF), chosen as a representative drug due to its poor water solubility, was encapsulated into SLNs composed of stearic acid. Optimization of chitosan-coated GF-loaded SLNs (CS-GF-SLN) was conducted using a Box-Behnken design. Utilizing the desirability approach, optimal parameters were determined, including a lipid quantity of 450.593 mg, chitosan content of 268.67 mg, and sonication duration of 2.14 hours. These parameters resulted in a zeta potential of -34.8 mV and a particle size (PS) of 56.87 nm. Following optimization, the refined formulation underwent comprehensive assessment across various parameters. Notably, the drug encapsulated within SLNs exhibited sustained release over three days, as illustrated by the in-vitro drug release profile. The optimized formulation demonstrated a bioavailability enhancement by approximately 1.7 to 2.0 times compared to the conventional formulation. Furthermore, administration of drug-loaded SLNs to a macrophage cell line demonstrated no cytotoxicity, affirming their suitability as conventional drug delivery platforms for GF.