Nanosuspensions Research Articles

Albumin and Polysorbate-80 Coated Sterile Nanosuspensions of Mebendazole for Glioblastoma Therapy.

The scarcity of existing and novel therapies for brain cancer has significantly affected the survival rate of glioblastoma patients. Mebendazole (MBZ), an antiparasitic agent demonstrated promising activity against brain cancer. However, poor solubility, multiple polymorphs, and insufficient permeability through blood-brain barrier (BBB) restricts its therapeutic efficacy through parenteral administration. The current study aimed to develop, optimize, and characterize sterile, injectable nanosuspension of mebendazole using parenterally acceptable stabilizers. Albumin and polysorbate 80 (PS-80) coated MBZ Nanosuspension (NS) was prepared using wet media milling technique. Design of experiment (DoE) approach was used to understand effect of drug loading versus stabilizer concentration. The optimized MBZ NS showed hydrodynamic diameter of 208.36 ± 0.24 nm with a poly dispersibility index (PDI) of 0.210 ± 0.03 and zeta potential of -20.41 ± 0.36 mV. The IC50 value of MBZ NS in U-87 MG and LN-229 cell lines were found to be 0.49 ± 0.02 μM and 0.48 ± 0.05 μM, respectively. Additionally, MBZ NS demonstrated a 2.65-fold decrease in colony-forming efficiency and a 1.16-fold reduction in migration of the bridging area compared to MBZ. In 3D spheroids of the U-87 MG glioma cell line, MBZ NS exhibited a 50% reduction in tumor growth and increased cell apoptosis compared to the control. MBZ NS formulations were sterilized by gamma irradiation and tested as per the USP sterility test. Albumin-PS 80 coated NS is rendered to be useful parenteral delivery of mebendazole for the treatment of brain cancer.

Nanosuspension: A Novel Drug Delivery System

It is over past two years ago. It has technology has been developed R& D pharmaceutical business. Nanotechnology is science is deals with the process that occurs at Molecular level and Nanolength scale size, Nano refer to the particle size range is 1- 1000 micrometre. Nano suspension can be used in oral, topical parenteral and pulmonary route of administration of drug delivery, Nano suspension is used in incorporated into ocular inserts and mucoadhesive hydrocele for targeted drug delivery. There are medication candidate is with very high effectiveness. Nanosuspension was prepared by using combination of high speed homogenization (HSH) and media milling (MM),Poligomer( stabilizer)ZIO2 heads ( milling media). Reducing particle size in Nanosuspension is the primary cause of an increase in .Because of their specific qualities, nanosuspension can be used in a variety of dosage forms, including ones that require specialised delivery methods like mucoadhesive hydrogels.The Atomization of the drug discovery process through technologies like computer-aid drug design, combinatorial chemistry, an high-throughput screening is producing a large number of very effective therapeutic candidates. Regrettably, a lot of these potentiate medications are not very soluble in water. This review article describes the physicochemical properties of drug Nanosuspension, preparation methods and; it’s potential clinical advantages.

Albendazole nanosuspension coated granules for the rapid localized release and treatment of colorectal cancer

Albendazole (ABZ), an anthelmintic drug, has been repurposed to treat various types of cancers. However, poor solubility of ABZ, resulting in low bioavailability, limits its application. Nanosuspension is a versatile method for enhancing the dissolution of hydrophobic molecules, but a successful drying has been the biggest challenge in the field. The objective of this research is to formulate and optimize ABZ nanosuspension (NS) coated granules for rapid delivery of ABZ for the treatment of colorectal cancer. ABZ NS was prepared by dual centrifugation method using Kollidon® VA64 and sodium lauryl sulphate (SLS) as stabilizers. The processing method was optimized to obtain a stable nanosuspension with particle size < 300 nm. The optimized ABZ NS was coated on microcrystalline cellulose (MCC) to form the nano-coated granules (NCG) and filled in EUDRACAP® for colon targeted delivery. The ABZ NS and NCG achieved ∼ 60 % and ∼55 % drug release, respectively, in presence of bile salt at colonic pH. Half-maximal inhibitory concentration (IC50) of ABZ NS was found to be 1.18 ± 0.081 µM and 3.59 ± 0.080 µM in two colorectal cancer cell lines: HCT 116 and HT-29, respectively. In addition, In vitro 3D tumor assay revealed that ABZ NS has superior tumor growth inhibition activity compared to the control and pure ABZ. The preparation of ABZ NCG in EUDRACAP® could be a promising approach to achieve colon targeted delivery and to repurpose ABZ for the treatment of colorectal cancer.

Heat transfer in a non-uniformly heated enclosure filled by NEPCM water nanofluid

PurposeThis paper aims to focuses on by investigate the heat transmission and free convective flow of a suspension of nano encapsulated phase change materials (NEPCMs) within an enclosure. Particles of NEPCM have a core-shell structure, with phase change material (PCM) serving as the core.Design/methodology/approachThe enclosure consists of a square chamber with an insulated wall on top and bottom and vertical walls that are differently heated. The governing equations are investigated using the finite element technique. A grid inspection and validation test are done to confirm the precision of the results.FindingsThe effects of fusion temperature (varying from 0.1 to 0.9), Stefan number (changing from 0.2 to 0.7), Rayleigh number (varying from 103 to 106) and volume fraction of NEPCM nanoparticles (changing from 0 to 0.05) on the streamlines, isotherms, heat capacity ratio and average Nusselt number are investigated using graphs and tables. From this investigation, it is found that using a NEPCM nano suspension results in a significant enhancement in heat transfer compared to pure fluid. This augmentation becomes more important for the low Stefan number, which is around 16.57% approximately at 0.2. Secondary recirculation is formed near the upper left corner as a result of non-uniform heating of the left vertical border. This eddy expands notably as the Rayleigh number rises. The study findings indicate that the NEPCM nanosuspension has the potential to act as a smart working fluid, significantly enhancing average Nusselt numbers in enclosed chambers.Research limitations/implicationsThe NEPCM particle consists of a core (n-octadecane, a phase-change material) and a shell (PMMA, an encapsulation material). The host fluid water and the NEPCM particles are considered to form a dilute suspension.Practical implicationsUsing NEPCMs in energy storage thermal systems show potential for improving heat transfer efficiency in several engineering applications. NEPCMs merge the beneficial characteristics of PCMs with the enhanced thermal conductivity of nanoparticles, providing a flexible alternative for effective thermal energy storage and control.Originality/valueThis paper aims to explore the free convective flow and heat transmission of NEPCM water-type nanofluid in a square chamber with an insulated top boundary, a uniformly heated bottom boundary, a cooled right boundary and a non-uniformly heated left boundary.

Formulation and Evaluation of Nano Suspension Based Oro Disoersible Film of Aripiprazole

The present study was aimed to enhance the solubility and dissolution of BCS class 4 drug aripiprazole, by nano formulation approach. Acid-base neutralization method had been used to produced nanosuspension. The nanosuspensions remained stable without any aggregations with particle size 209.6nm and PDI 0.247. Zeta potential was found to be 3.5mV. Drug content, Entrapment and solubility of nanosuspension formulations were determined. In vitro drug release of the selected formulation has shown a drug release of 95.63% by the end of 1 hr, whereas plain drug suspension has shown only 12.3% release. XRD and DSC studies revealed that the solid form of aripiprazole altered from the crystalline state to the amorphous state after incorporation into nanosuspensions. Hence, from the results, it can be concluded that Aripiprazole, when formulated by acid-base neutralization method as a nanosuspension, leads to enhanced solubility, dissolution, and stability

Novel inhalable nano-based/microparticles for enhanced sustained pulmonary delivery of remdesivir - A patient malleable treatment for coronaviruses infection: In vitro aerosolization, cytotoxicity assays and antiviral activity studies

Remdesivir (RDV) is an antiviral used in potential treatment of SARS-COV-2 infection during the COVID-19 pandemic worldwide. However, it is still limited to IV administration for hospitalized patients. Therefore, we report herein successful development of RDV-loaded nanosuspensions (NS) using polycaprolactone and pluronic® F127, for the first time. The optimized RDV-NS was further loaded into inhalable nano-based/microparticles (OLN-microparticles) via co-spray drying with hyaluronic acid and mannitol. OLN-microparticles exhibited high yield value ∼80.56 %, with satisfactory entrapment efficiency and drug loading percent ∼97.27 ± 1.84 % and 3.92 ± 0.07 %, respectively. Carr's index was equal to 22.7 ± 11.67 % indicating good flowability properties. Scanning electron microscopic analysis showed spherical-shaped particles. Transmission electron microscope demonstrated grape-shaped clumps surface porosity. OLN-microparticles exhibited excellent aerodynamic features including; emitted fraction ∼97.46 ± 1.70 %, respirable particle fraction 53.77 ± 0.2 %, effective inhalation index 72.39 ± 1.40 %, and mass median aerodynamic diameter 2.25 ± 0.01 μm. Compared to plain RDV, OLN-microparticles showed significantly enhanced sustained release (p < 0.0001) with 1.5 and 1.9 fold increase at 24 and 48 h, respectively in Gamble's solution. OLN-microparticles also showed favorable cytotoxic profile with CC50 ∼ 252.0 μg/mL, inhibitory concentration (IC50) 13.08 μg/mL, and safety index (SI) 19.26 which is 1.3 fold higher compared to plain RDV. The Optimal release profile of OLN-microparticles enabled controlled and sustained release with enhanced cellular uptake. Hence, OLN-microparticles represented an efficient alternative form of dry powder for inhalation for deep and targeted pulmonary delivery of RDV, outweighing limitations accompanied with IV administration. It can provide self-administered and malleable access of treatment for SARS-COV-2 infected patients.

Deferasirox nanosuspension loaded dissolving microneedles for ocular drug delivery

Deferasirox (DFS) is an oral iron chelator that is employed in retinal ailments as a neuroprotectant against retinal injury and thus has utility in treating disorders such as excitoneurotoxicity and age-related macular degeneration (AMD). However, the conventional oral route of administration can present several disadvantages, e.g., the need for more frequent dosing and the first-pass effect. Microneedles (MNs) are minimally invasive systems that can be employed for intrascleral drug delivery without pain and can advantageously replace intravitreal injections therapy (IVT) as well as conventional oral routes of delivery for DFS. In this study, DFS was formulated into a nanosuspension (NS) through wet media milling employing PVA as a stabilizer, which was successfully loaded into polymeric dissolving MNs. DFS exhibited a 4-fold increase in solubility in DFS-NS compared to that of pure DFS. Moreover, the DFS-NSs exhibited excellent short-term stability and enhanced thermal stability, as confirmed through thermogravimetric analysis (TGA) studies. The mechanical characterization of the DFS-NS loaded ocular microneedles (DFS-NS-OcMNs), revealed that the system was sufficiently strong for effective scleral penetration. Optical coherence tomography (OCT) images confirmed the insertion of 81.23 ± 7.35 % of the total height of the MN arrays into full-thickness porcine sclera. Scleral deposition studies revealed 64 % drug deposition after just 5 min of insertion from DFS-NS-loaded ocular microneedles (OcMNs), which was almost 5 times greater than the deposition from pure DFS-OcMNs. Furthermore, both DFS and DFS-NS-OcMN exhibited remarkable cell viability when evaluated on human retinal pigment (ARPE) cells, suggesting their safety and appropriateness for use in the human eye. Therefore, loading DFS-NS into novel MN devices is a promising technique for effectively delivering DFS to the posterior segment of the eye in a minimally invasive manner.

Organic solvent-free benznidazole nanosuspension as an approach to a novel pediatric formulation for Chagas disease.

Aim: Benznidazole (BNZ), a class-II drug, is the primary treatment for Chagas disease, but its low aqueous solubility presents challenges in formulation and efficacy. Nanosuspensions (NS) could potentially address these issues.Methods: BNZ-NS were prepared using a simple, organic solvents-free nano-milling approach. Physicochemical characterizations were conducted on both NS and lyophilized solid-state BNZ-nanocrystals (NC).Results: BNZ-NS exhibited particle size <500nm, an acceptable polydispersity index (0.23), high Z-potential, and physical stability for at least 90days. BNZ-NC showed tenfold higher solubility than pure BNZ. Dissolution assays revealed rapid BNZ-NS dissolution. BNZ-NC demonstrated biocompatibility on an eukaryotic cell and enhanced BNZ efficacy against trypomastigotes of Trypanosoma cruzi.Conclusion: BNZ-NS offers a promising alternative, overcoming limitations associated with BNZ for optimized pharmacotherapy.

Dissolving microarray patches loaded with a rotigotine nanosuspension: A potential alternative to Neupro® patch

Parkinson's disease (PD), affecting about ten million people globally, presents a significant health challenge. Rotigotine (RTG), a dopamine agonist, is currently administered as a transdermal patch (Neupro®) for PD treatment, but the daily application can be burdensome and cause skin irritation. This study introduces a combinatorial approach of dissolving microarray patch (MAP) and nanosuspension (NS) for the transdermal delivery of RTG, offering an alternative to Neupro®. The RTG-NS was formulated using a miniaturized media milling method, resulting in a nano-formulation with a mean particle size of 274.09 ± 7.43 nm, a PDI of 0.17 ± 0.04 and a zeta potential of −15.24 ± 2.86 mV. The in vitro dissolution study revealed an enhanced dissolution rate of the RTG-NS in comparison to the coarse RTG powder, under sink condition. The RTG-NS MAPs, containing a drug layer and a ‘drug-free’ supporting baseplate, have a drug content of 3.06 ± 0.15 mg/0.5 cm2 and demonstrated greater amount of drug delivered per unit area (∼0.52 mg/0.5 cm2) than Neupro® (∼0.20 mg/1 cm2) in an ex vivo Franz cell study using full-thickness neonatal porcine skin. The in vivo pharmacokinetic studies demonstrated that RTG-NS MAPs, though smaller (2 cm2 for dissolving MAPs and 6 cm2 for Neupro®), delivered drug levels comparable to Neupro®, indicating higher efficiency per unit area. This could potentially avoid unnecessarily high plasma levels after the next dose at 24 h, highlighting the benefits of dissolving MAPs over conventional transdermal patches in PD treatment.

Preparation and Characterization of Febuxostat Nanosuspension as Fast Dissolving Oral Film

Background: Quickly dissolved oral films are a widely accepted method of delivering drugs and help patients adhere to treatment regimens. Nanosuspensions (NS) are colloidal dispersions of drug particles with a submicron size, and their large surface area enhances the solubility and dissolution of low-water-soluble drugs. Febuxostat (FXT) is a non-purine xanthine oxidase inhibitor with a low dissolution rate that limits its absorption. Objective: To develop fast-dissolving oral films (FDOFs) containing FXT NS and convert NS into solid dosage forms to ease administration and accelerate drug release. Methods: FXT NS was prepared using Soluplus as a stabilizer and Tween80 as a co-stabilizer through an anti-solvent precipitation technique. We prepared FDOFs using a solvent casting method, utilizing hydrophilic polymers like pullulan, polyvinyl alcohol (PVA), gelatin, and plasticizers like polyethylene glycol (PEG400) and glycerin. The study assessed the film's thickness, weight, folding endurance, drug content, disintegration time, and drug release. We validated the drug's compatibility using FTIR, and conducted a crystallinity study using DSC and X-ray powder diffraction. Results: F4 was the optimized formula prepared using PVA and PEG400. In just three minutes, the F4 dissolution rate increased significantly (99.63% vs. 11.23%) compared to the FXT ordinary film. Also, it had good mechanical properties. Conclusions: FXT NS were successfully loaded into FDOFs with accepted properties.

Nanosuspensions: A Novel Drug Delivery System

The current article cites the importance of the emerging and promising future of new age dosage form, ‘nano suspensions’. Particle size reduction, particularly nanonization, is a non-specific, universal approach to improve the bioavailability of poorly soluble drugs. The article emphasizes importance in the preparation, evaluation and the research work going on with various drugs and their appropriate applications. Nano suspensions have emerged as a promising strategy for the efficient delivery of hydrophobic drugs because of their versatile features and unique advantages. Techniques such as media milling and high-pressure homogenization have been used commercially for producing nano suspensions. The unique features of nano suspensions have enabled their use in various dosage forms, including specialized delivery systems such as mucoadhesive hydrogels. Rapid strides have been made in the delivery of nano suspensions by parenteral, peroral, ocular and pulmonary routes. Currently, efforts are being directed to extending their applications in site-specific drug delivery.

Formulation and Characterization of Clozapine Nanosuspension as a Sublingual Film

Background: Clozapine (CLZ) is a potent antipsychotic drug that suppresses the symptoms of schizophrenia and mania. Clozapine falls into Class II (BCS); its poor bioavailability is attributed to low water solubility and an extensive first-pass effect. Objective: To prepare CLZ as a nanosuspension (NS) to improve its low water solubility and load it into a sublingual film to enhance oral bioavailability. Methods: CLZ nanosuspensions are prepared by the “solvent anti-solvent precipitation” method using Soluplus as a stabilizing agent. We evaluated the polydispersity index (PDI) and the particle size of the CLZ nanosuspension formulations. The optimized formula of CLZ nanosuspension is loaded directly onto a sublingual thin film, eliminating the need for freeze-drying for solidification by the solvent casting approach. The sublingual films were characterized by thickness, surface pH, folding endurance, disintegration time, and in vitro dissolution rate. Results: We selected the formula F1 sublingual film as the best, as it demonstrated a uniform thickness of 0.087mm, good flexibility, and a surface pH of 6.7. It disintegrated quickly in 13 seconds and had a faster in vitro dissolution rate (3 min) compared to the CLZ ordinary films. Conclusions: The results confirmed the success of CLZ NS as a sublingual thin film for dissolution rate enhancement, which may improve oral bioavailability.

Calcipotriol Nanosuspension-Loaded Trilayer Dissolving Microneedle Patches for the Treatment of Psoriasis: In Vitro Delivery and In Vivo Antipsoriatic Activity Studies.

Psoriasis, affecting 2-3% of the global population, is a chronic inflammatory skin condition without a definitive cure. Current treatments focus on managing symptoms. Recognizing the need for innovative drug delivery methods to enhance patient adherence, this study explores a new approach using calcipotriol monohydrate (CPM), a primary topical treatment for psoriasis. Despite its effectiveness, CPM's therapeutic potential is often limited by factors like the greasiness of topical applications, poor skin permeability, low skin retention, and lack of controlled delivery. To overcome these challenges, the study introduces CPM in the form of nanosuspensions (NSs), characterized by an average particle size of 211 ± 2 nm. These CPM NSs are then incorporated into a trilayer dissolving microneedle patch (MAP) made from poly(vinylpyrrolidone) and w poly(vinyl alcohol) as needle arrays and prefrom 3D printed polylactic acid backing layer. This MAP features rapidly dissolving tips and exhibits good mechanical properties and insertion capability with delivery efficiency compared to the conventional Daivonex ointment. The effectiveness of this novel MAP was tested on Sprague-Dawley rats with imiquimod-induced psoriasis, demonstrating efficacy comparable to the marketed ointment. This innovative trilayer dissolving MAP represents a promising new local delivery system for calcipotriol, potentially revolutionizing psoriasis treatment by enhancing drug delivery and patient compliance.

Locally administered nanosuspension increases delivery of estradiol for the treatment of vaginal atrophy in mice.

Vaginal atrophy affects up to 57% of post-menopausal women, with symptoms ranging from vaginal burning to dysuria. Estradiol hormone replacement therapy may be prescribed to alleviate these symptoms, though many vaginal products have drawbacks including increased discharge and local tissue toxicity due to their hypertonic nature. Here, we describe the development and characterization of a Pluronic F127-coated estradiol nanosuspension (NS) formulation for improved vaginal estradiol delivery. We compare the pharmacokinetics to the clinical comparator vaginal cream (Estrace) and demonstrate increased delivery of estradiol to the vaginal tissue. We utilized ovariectomized (OVX) mice as a murine model of post-menopausal vaginal atrophy and demonstrated equivalent efficacy in vaginal re-epithelialization when dosed with either the estradiol NS or Estrace cream. Further, we demonstrate compatibility of the estradiol NS with vaginal bacteria in vitro. We demonstrate that a Pluronic F127-coated estradiol NS may be a viable option for the treatment of post-menopausal vaginal atrophy.

Insight into the bidirectional dynamics of hyperbolic tangent hybrid nanomaterial subject to Nield’s conditions using numerical approach

A hyperbolic tangent fluid model characterized by shear rate dependent viscosity together with the effects of hybrid nanoparticles, Brownian motion, thermo-diffusion, and Nield’s conditions, is utilized for thermal enhancement purpose. Five percent copper nanoparticles and twenty percent alumina nanoparticles are submerged into ethylene glycol with the parametric influence of tangent hyperbolic fluid to obtain the tangent hyperbolic hybrid nano suspension. Numerical solutions of the nondimensionalized conservation laws are found by the Keller-box method. The influence of various parametric factors on velocity, temperature, concentration, Nusselt number, and Sherwood number has been discussed. A constant Nusselt number is noted with the influence of Nield’s constraints. A 90% increase in thermal conductivity is achieved by dispersing 5% copper and 20% alumina nanoparticles into the ethylene glycol with the influence of hyperbolic tangent fluid. The error and convergence analysis of the numerical solution have been discussed, along with the validation of the obtained numerical results.

Tannic acid coated nanosuspension for oral delivery of chrysin intended for anti-schizophrenic effect in mice

Chrysin is a flavonoid drug with numerous therapeutic activities. It suffers from low intestinal absorption owing to its hydrophobicity. Therefore, the aim of this study is to exploit the efficient technique of nanosuspension (NSP) to formulate chrysin-NSP coated with tannic acid (TA) to improve the solubility and anti-schizophrenic activity of chrysin. A 23 full factorial design was constructed where the independent factors were type of polymer, surfactant concentration (0.5 or 1 %) and the aqueous phase volume (5 or 15 mL), while the dependent responses were the particle size (PS) of the obtained formulation as well as the % chrysin dissolved after 2 h (Q2h). The optimum formulation (NSP-4) composed of 1 % PEG 400 and 1 % Cremophor RH40 in 15 mL aqueous phase. It achieved a PS and Q2h values of 108.00 nm and 38.77 %, respectively. NSP-4 was then coated with TA (TA-coated NSP-4) for further enhancement of chrysin solubility. TA-coated NSP-4 revealed PS and zeta potential values of 150 ± 14 nm and –32.54 ± 2.45 mV, respectively. After 6 h, chrysin dissolved % were 53.97 and 80.22 for uncoated NSP-4 and TA-coated NSP-4, respectively, compared with only 9.47 for free chrysin. The developed formulations and free chrysin were assessed regarding their effect on schizophrenia induced in mice by cuprizone (CPZ). Treatment with the developed formulations and free chrysin ameliorated demyelination and behavioral deficit induced by CPZ via elevating MBP and PI3K/PKC activities as well as reducing GFAP expression levels. The developed formulations and free chrysin inhibited Galactin-3 and TGF-β expressions and stimulated GST antioxidant enzyme. Furthermore, they maintained the balances in glutamatergic and dopaminergic neurotransmission via modulation on neuregulin-1 and alleviated nuclear pyknosis and degeneration in the neurons. The order of activity was: TA-coated NSP-4 > NSP-4 > free chrysin.

Current Insights of Nano Suspension Drug Delivery System: A Patent Review

Unfortunately, water-solvency continues to be a usual characteristic of medication newcomers in medicine improvement pipelines today. Different cycles have been established to improve the solvency, disintegrating rate, and bioavailability associated with these dynamic fixes having a place utilizing the biopharmaceutics classification system (BCS) II through IV orders. Since the mid-2000s, nanosuspension, nanocrystal delivery, and nebulous strong scatterings have been more established approaches to overcome the obstructions of ineffective water solvent pharmaceuticals in food and drug administration (FDA) accessible goods. This work supplies a refreshed examination of nanosuspension and dissimilar strong scattering methods, particularly for orally conveyed medications. Moreover, solvency is a vital variable for medication adequacy, autonomously of the course of development. Ineffectively solvent drugs are many times difficult assignments for developers within the sector. Customary methods to improve solvency are of little significance, specifically when the pharmaceuticals are ineffectively liquid all the while they’re watery as well as non-fluid mediums. Nanosuspension technology can be employed to enhance the potency and solubility with insoluble substances medicines. Nanosuspension possesses dual-phase structures made up of precise medication particles scattered throughout a liquid medium kept in check with surfactants. Those strategies generally straightforward plan offer advantages compared to alternative methods. Various methods, comprising wet manufacturing, regions assembling, emulsifying, evaporating the solvent, and releasing simple liquid methods, are employed when making nanosuspension. Subsequently enjoys convenience conveyance via diverse courses, comprising oral, parenteral, aspiratory even visual courses. The current proposal plan provide the ongoing strategies employed to get ready small suspensions, including their application in medication conveyance

Design of High-Payload Ascorbyl Palmitate Nanosuspensions for Enhanced Skin Delivery.

A high-payload ascorbyl palmitate (AP) nanosuspension (NS) was designed to improve skin delivery following topical application. The AP-loaded NS systems were prepared using the bead-milling technique, and softly thickened into NS-loaded gel (NS-G) using hydrophilic polymers. The optimized NS-G system consisted of up to 75 mg/mL of AP, 0.5% w/v of polyoxyl-40 hydrogenated castor oil (Kolliphor® RH40) as the suspending agent, and 1.0% w/v of sodium carboxymethyl cellulose (Na.CMC 700 K) as the thickening agent, in citrate buffer (pH 4.5). The NS-G system was embodied as follows: long and flaky nanocrystals, 493.2 nm in size, -48.7 mV in zeta potential, and 2.3 cP of viscosity with a shear rate of 100 s-1. Both NS and NS-G provided rapid dissolution of the poorly water-soluble antioxidant, which was comparable to that of the microemulsion gel (ME-G) containing AP in solubilized form. In an ex vivo skin absorption study using the Franz diffusion cell mounted on porcine skin, NS-G exhibited faster absorption in skin, providing approximately 4, 3, and 1.4 times larger accumulation than that of ME-G at 3, 6, and 12 h, respectively. Therefore, the high-payload NS makes it a promising platform for skin delivery of the lipid derivative of ascorbic acid.

Development of Cyclosporine A Nanosuspension Using an Experimental Design Based on Response Surface Methodology: In Vitro Evaluations.

This study aimed to develop nanosuspensions (NSs) of cyclosporine A (CycA) using a top-down technology [high-pressure homogenization-(HPH)] for oral administration. Formulas were prepared using different ratios of hydroxypropyl methylcellulose (HPMC) (1% and 0.5%) and sodium dodecyl sulfate (SDS) (1%) to improve the solubility of CycA. The HPH method was optimized by investigating the effects of critical formulation parameters (stabilizer ratio) and critical process parameters (number of homogenization cycles) on the particle size (PS), polydispersity index (PDI), and zeta potential (ZP) of NS using the Design of Experiment (DoE). After lyophilization, differential scanning calorimetry, X-ray diffraction, fourier-transform infrared spectroscopy, and morphological evaluation with scanning electron microscopy were performed. Stability studies were conducted at 4 °C and 25 °C storage conditions. The solubility of the optimum CycA NS was investigated by comparing it with a coarse CycA powder and a physical mixture (PM). In vitro dissolution studies were conducted in four media using United States Pharmacopeia apparatus I. PS, PDI, and ZP values for the NS were approximately 250 nm, 0.6, and 35 mV, respectively. Under storage conditions, the CycA NS exhibited significant physical stability at both 4 °C and 25 °C for 9 months. The solubility of CycA was improved 1.9 and 1.4 times by NS in the presence of CycA powder and PM, respectively. CycA NS exhibited higher dissolution than CycA coarse powder in 0.1 N HCl, fasted simulated intestinal fluid, and fed simulated intestinal fluid. CycA NS was successfully developed using the DoE approach with the HPH method with HPMC:SDS combination in a 1:0.5 ratio, and the solubility and dissolution of CycA in the NS were improved.

Development of rapidly soluble mebendazole nanosuspension for colorectal cancer

Mebendazole (MBZ) has been proven as a repurposing molecule against colorectal cancer. Unfortunately, its clinical application is constrained by its extremely poor solubility and bioavailability. The aim of the current work was to augment the dissolution rate at colonic pH and the anticancer efficacy by formulating MBZ nanosuspension (NS). A robust MBZ NS was developed using a combination of Sodium Lauryl Sulphate (SLS) and Hydroxy Propyl Methyl Cellulose E5 (HPMC) as stabilizers through the dual centrifugation method. The prepared MBZ NS exhibited the smallest particle size (362.6 ± 12.3 nm) with unimodal particle size distribution and excellent short-term stability. DSC and FT-IR studies confirmed the crystallinity and the absence of interactions with the stabilizers used. The developed MBZ NS demonstrated ∼20 folds higher dissolution than MBZ alone in colonic pH. Cell experiments showed that HPMC E5 and SLS were safe on HT-29 and HT-116 cell lines. In addition, IC50 of MBZ-NS was found to be 1.028 ± 0.030 μM and 0.884 ± 0.050 μM in HT-29 and HT-116 cell lines, respectively. Furthermore, 1.5 folds and 1.8 folds reduction in 3D tumor spheroids after treatment with MBZ-NS was observed compared to the control and MBZ physical mixture. From the In Vitro Live/Dead Cell Assay higher amount of red fluorescence in treatment groups confirmed a large number of dead cells compared to the control. In a nutshell, the produced MBZ NS could be employed as a promising formulation to achieve a higher dissolution rate and anticancer efficacy against colorectal cancer of repurposing drug MBZ.