Minoxidil Nanosuspension-Loaded Dissolved Microneedles for Hair Regrowth.

Minoxidil (MIN) is used topically to treat alopecia. However, its low absorption limits its use, warranting a new strategy to enhance its delivery into skin layers. The objective of this study was to evaluate the dermal delivery of MIN by utilizing dissolved microneedles (MNs) loaded with MIN nanosuspension (MIN-NS) for hair regrowth. MIN-NS was prepared by the solvent-antisolvent precipitation technique. The particle size of MIN-NS was 226.7 ± 9.3 nm with a polydispersity index of 0.29 ± 0.17 and a zeta potential of -29.97 ± 1.23 mV. An optimized formulation of MIN-NS was selected, freeze-dried, and loaded into MNs fabricated with sodium carboxymethyl cellulose (Na CMC) polymeric solutions (MIN-NS-loaded MNs). MNs were evaluated for morphology, dissolution rate, skin insertion, drug content, mechanical properties, ex vivo permeation, in vivo, and stability studies. MNs, prepared with 14% Na CMC, were able to withstand a compression force of 32 N for 30 s, penetrate Parafilm M® sheet at a depth of 374-504 µm, and dissolve completely in the skin within 30 min with MIN %recovery of 95.1 ± 6.5%. The release of MIN from MIN-NS-loaded MNs was controlled for 24 h. MIN-NS-loaded MNs were able to maintain their mechanical properties and chemical stability for 4 weeks, when kept at different storage conditions. The in vivo study of the freeze-dried MIN-NS and MIN-NS-loaded MNs proved hair regrowth on rat skin after 11 and 7 days, respectively. These results showed that MIN-NS-loaded MNs could potentially improve the dermal delivery of MIN through the skin to treat alopecia.

Throat spray formulated with virucidal Pharmaceutical excipients as an effective early prophylactic or treatment strategy against pharyngitis post-exposure to SARS CoV-2.

Our study aimed to develop a virucidal throat spray using bioactive compounds and excipients, focusing on the preparation of Curcumin (CUR) in a self-nano emulsifying drug delivery system (SNEDDS). Two molecular docking studies against SARS-CoV-2 targets guided the selection of proper oil, surfactant, co-surfactant, and natural bioactive that would maximize the antiviral activity of the throat spray. Two self-nanoemulsifying formulas that were diluted with different vehicles to prepare eight CUR-loaded SNESNS (self-nanoemulsifying self-nanosuspension) formulas. In vitro characterization studies and in vitro anti-SARS-CoV-2 effect revealed that the optimal formula, consisted of 20 % Anise oil, 70 % Tween 80, 10 % PEG 400, and 0.1 %w/w CUR, diluted with DEAE-Dx. Preclinical toxicity tests on male rats confirmed the safety of a mild throat spray dose (5 µg/mL CUR). In a rat model of acute pharyngitis induced by ammonia, post-treatment with the optimal formula of CUR loaded SNESNS for one week significantly reduced elevated proinflammatory markers (TNF-α, IL6, MCP1, and IL8). In conclusion, our CUR-loaded SNESNS formula, at 5 µg/mL concentration, shows promising effect as a prophylactic throat spray against SARS-CoV-2 and as a treatment for pharyngitis.

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-ß 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.

Preparations of 25 wt% of Pyraclostrobin Nanosuspension Concentrate (SC) Using Lignosulfonate-Based Colloidal Spheres to Improve Its Thermal Storage Stability.

Improving the thermal storage stability of nanosuspension concentrate (SC) prepared from low-melting-point pesticide is a recognized problem. In this work, using pyraclostrobin as the raw material, 25 wt% of pyraclostrobin nano-SC was prepared through a water-based grinding method, and the optimal grinding conditions were obtained as follows: a grinding time of 23 h, D-3911 as dispersant and a dispersant dosage of 12 wt%. The pyraclostrobin nano-SC D90 size prepared based on this best formula was 216 nm. Adding glycerin could improve the stability of nano-SC at room temperature, but its thermal storage stability was still poor. For this problem, sodium lignosulfonate and cetyltrimethylammonium bromide (NaLS/CTAB) colloidal spheres were prepared through electrostatic and hydrophobic self-assembly and characterized. The delamination and precipitation of nano-SC can be significantly improved by adding an appropriate amount of colloidal spheres, and the nano-SC D90 size decreased from 2726 to 1023 nm after 7 days of thermal storage. Farmland experiments indicated the control efficiency of pyraclostrobin nano-SC against flowering cabbage downy mildew disease was about 30% higher than that of SC. Especially after adding the wetting agent, the effect of nano-SC could be comparable to that of commercial Kairun (currently the best pyraclostrobin formulation in the world).

Polydispersity-mediated high efficacy of an in-situ aqueous nanosuspension of PPEF.3HCl in methicillin resistant Staphylococcus aureus sepsis model.

Recently, World Health Organization declared antimicrobial resistance as the third greatest threat to human health. Absence of known cross-resistance, new class, new target, and a new mode of action are few major strategies being undertaken by researches to combat multidrug resistant pathogen. PPEF.3HCl, a bisbenzimidazole was developed as highly potent antibacterial agent against ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens, targeting topoisomerase IA. The present work encompasses a radical on-site generation of In-situ nanosuspension of PPEF.3HCl with enhanced efficacy against methicillin resistant S. aureus in septicemia model. We have generated instantaneously a PPEF.3HCl nanosuspension (IsPPEF.3HCl-NS) by mixing optimized monophasic PPEF.3HCl preconcentrate in propylene glycol into an aqueous medium comprising tween 80 as stabilizer. The IsPPEF.3HCl-NS showed precipitation efficiency of > 90 %, average particle size < 500 nm, retained upto 5 h, a negative zeta potential and bi/trimodal particle size distribution. Differential scanning calorimetry, X-ray diffraction confirmed partial amorphization and transmission electron microscopy revealed spherical particles. IsPPEF.3HCl-NS was non-hemolytic and exhibited good stability in serum. More significantly, it exhibited a âˆ¼ 1.6-fold increase in macrophage uptake compared to free PPEF.3HCl in the RAW 264.7 macrophage cell line. Confocal microscopy revealed accumulation of IsPPEF.3HCl-NS within the lysosomal compartment and cell cytosol, proposing high efficacy. In terms of antimicrobial efficacy, IsPPEF.3HCl-NS outperforms free PPEF.3HCl against clinical methicillin sensitive and resistant S. aureus strains. In a pivotal experiment, IsPPEF.3HCl-NS exhibited over 83 % survival at 8 mg/kg.bw and an impressive reduction of âˆ¼ 4-5 log-fold in bacterial load, primarily in the kidney, liver and spleen of septicemia mice. IsPPEF.3HCl-NS prepared by the In-situ approach, coupled with enhanced intramacrophage delivery and superior efficacy, positions IsPPEF.3HCl-NS as a pioneering and highly promising formulation in the battle against antimicrobial resistance.

Development of a Resveratrol Nanoformulation for the Treatment of Diabetic Retinopathy.

Diabetic retinopathy (RD) is a microvascular disease that can cause the formation of fragile neovessels, increasing the risk of hemorrhages and leading to vision loss. Current therapies are based on the intravitreal injection of anti-VEGF (vascular endothelial growth factor), which is invasive and can cause secondary effects. The development of new treatments that complement the current therapies is necessary to improve the patient's outcomes. Nanostructured formulations offer several advantages regarding drug delivery and penetration. In this research, a resveratrol nanosuspension (RSV-NS) was prepared and characterized using dynamic light scattering, field emission scanning electron microscopy, and infrared spectroscopy. The RSV-NS had an average particle size of 304.0 ± 81.21 nm with a PDI of 0.225 ± 0.036, and a spherical-like morphology and uniform particle distribution. Cell viability, proliferation, and migration were tested on endothelial cells (HMRECs). RSV-NS in a concentration of less than 18.75 µM did not have a cytotoxic effect on HMRECs. Likewise, proliferation and migration were significantly reduced compared to the unstimulated control at 37.5 µM. The RSV-NS did not present cytotoxic effects but decreased cell proliferation and migration, indicating that it could provide an important contribution to future medical implementations and could have a high potential to treat this disease.

Design Space and Control Strategy for the Manufacturing of Wet Media Milled Drug Nanocrystal Suspensions by Adopting Mechanistic Process Modeling.

Wet media milling is a fully industrialized technology for the manufacturing of drug nanocrystal suspensions. This work describes the development of an advanced control strategy and an associated design space for a manufacturing process at a commercial scale. Full-scale experiments and mechanistic process modeling have been used to establish a physically reasonable control strategy of factors relevant to the quality attributes of the nanocrystal suspension. The design space has been developed based on a mature mechanistic process model of the wet media milling procedure. It presents the process-product attribute relationship between a multidimensional range of measured process parameters and a range of the product-quality attribute mean particle sizes. The control strategy allows for simple, robust, and sound scientific process control as well as the operational flexibility of the suspension batch size. This is an industrial case study of control strategy and design-space definition with the crucial contribution of mechanistic process modeling for an intended commercial manufacturing process.

Herbal Nanoformulations for Diabetes: Mechanisms, Formulations, and Clinical Impact.

BACKGROUND: Diabetes mellitus remains a global health challenge, demanding innovative therapeutic strategies. Herbal remedies have garnered attention for their potential in diabetes management, and recent advancements in nanotechnology have enabled the development of herbal nanoformulations with enhanced efficacy and bioavailability. OBJECTIVE: This review aimed to comprehensively analyze the mechanisms, formulations, and clinical impact of herbal nanoformulations in managing diabetes mellitus. METHOD: A systematic literature search was conducted to identify relevant studies exploring the mechanisms of action, various formulations, and clinical outcomes of herbal nanoformulations in diabetes management. RESULT: Herbal nanoformulations exert their anti-diabetic effects through multiple mechanisms, including enhanced bioavailability, improved tissue targeting, and potentiation of insulin signaling pathways. Various herbal ingredients, such as bitter melon, fenugreek, and Gymnema sylvestre, have been encapsulated into nanocarriers, like liposomes, polymeric nanoparticles, and solid lipid nanoparticles, to enhance their therapeutic potential. Clinical studies have demonstrated promising results, showing improvements in glycemic control, lipid profile, and antioxidant status with minimal adverse effects. CONCLUSION: Herbal nanoformulations represent a promising avenue for the management of diabetes mellitus, offering improved therapeutic outcomes compared to conventional herbal preparations. Further research is warranted to optimize formulation strategies, elucidate long-term safety profiles, and explore the potential synergistic effects of herbal nanoformulations in combination therapies for diabetes management.

Nanocrystals and nanosuspensions: an exploration from classic formulations to advanced drug delivery systems.

Nanocrystals and nanosuspensions have become realistic approaches to overcome the formulation challenges of poorly water-soluble drugs. They also represent a less-known but versatile platform for multiple therapeutic applications. They can be integrated into a broad spectrum of drug delivery systems including tablets, hydrogels, microneedles, microparticles, or even functionalized liposomes. The recent progresses, challenges, and opportunities in this field are gathered originally together with an informative case study concerning an itraconazole nanosuspension-in-hydrogel formulation. The translational aspects, historical and current clinical perspectives are also critically reviewed here to shed light on the incoming generation of nanocrystal formulations.

A Biodegradable Nanosuspension Locally Used for Inhibiting Postoperative Recurrence and Brain Metastasis of Breast Cancer.

Addressing the urgent need to prevent breast cancer postoperative recurrence and brain metastasis, Fe-metal organic framework (MOF)-coated hollow mesoporous organosilica nanoparticles (HMON) with tumor microenvironment dual-responsive degradability were prepared to encapsulate doxorubicin (DOX), formulating a tissue-adhesive nanosuspension for perioperative topical medication. This nanosuspension can not only retain the sustainably released drug in the postoperative residual tumor sites but also enhance the intracellular oxidative stress of tumors for remarkable tumor ferroptosis. Interestingly, the nanosuspension can act as an immune amplifier, which could not only stimulate DC cells to secrete chemokines for T cell recruitment but also elevate antigen exposure to facilitate the antigen presentation in lymph nodes. Thus, this nanosuspension could significantly activate antitumor immune responses in both in situ tumors and metastatic encephaloma for enhanced immunotherapy. In conjunction with the clinical PD-1 antibody, the locally administered nanosuspension could achieve an advanced therapeutic outcome for inhibiting postoperative recurrence and metastasis.

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.

Effects of sepiolite addition to acrylic-latex paint on pull-off adhesion strength in nanosilver-impregnated and thermally-modified beech (Fagus orientalis L.) wood.

Sepiolite is a silicate mineral that improves the fire properties in solid wood when mixed with a water-based coating. The present study was carried out to investigate and evaluate the effects of sepiolite addition to acrylic-latex paint on the pull-off adhesion strength, as an important characteristic of paints and finishes used in the modern furniture industry and historical furniture as well for preservation and restoration of heritage objects. Sepiolite was added at the rate of 10%, and brushed onto plain-sawn beech (Fagus orientalis L.) wood specimens, unimpregnated and impregnated with a 400 ppm silver nano-suspension, which were further thermally modified at 185 °C for 4 h. The results showed that thermal modification had a decreasing effect on the pull-off adhesion strength, primarily as a result of the thermal degradation of cell-wall polymers (mostly hemicelluloses). Still, a decreased wettability as a result of condensation and plasticization of lignin was also partially influential. Based on the obtained results,thermal modification was found to have a significant influence on pull-off adhesion strength. Sepiolite addition had a decreasing effectin all treatments, though the effect was not statistically significant in all treatments. The maximum and minimum decreases due to sepiolite addition were observed in the unimpregnated control (21%) and the thermally-modified NS-impregnated (4%) specimens. Other aspects of the sepiolite addition, and further studies that cover different types of paints and coatings, should be evaluated before coming to a final firm conclusion in this regard.

Recent advances in nanocrystal-based technologies applied for ocular drug delivery.

INTRODUCTION: The intricate physiological barriers of the eye and the limited volume of eye drops impede efficient delivery of poorly water-soluble drugs. In the last decade, nanocrystals have emerged as versatile drug delivery systems in various administration routes from bench to bedside. The unique superiorities of nanocrystals, mainly embodied in high drug-loading capacity, good mucosal adhesion and penetration, and greatly improved drug solubility, reveal a promising prospect for ocular delivery of poorly water-soluble drugs. AREAS COVERED: This article focuses on the ophthalmic nanocrystal technologies and products that are in the literature, clinical trials, and even on the market. The recent research progress in the preparation, ocular application, and absorption of nanocrystals are highlighted, and the pros and cons of nanocrystals in overcoming the physiological barriers of the eye are also summarized. EXPERT OPINION: Nanocrystals have demonstrated success as glucocorticoid eye drops in the treatment of anterior segment diseases. However, the thermodynamic stability of nanocrystals remains the major challenge in product development. New technologies for efficiently optimizing stabilizers and sterilization processes are still expected. Strategies to confer more diverse functions via surface modification are also worth exploration to improve the potential of nanocrystals in delivering poorly water-soluble drugs to posterior segment of the eye.

Nanosuspension-Based Drug Delivery Systems for Topical Applications.

Nanosuspensions have garnered recent attention as a promising strategy for mitigating the bioavailability challenges of hydrophobic drugs, particularly those characterized by poor solubility in both aqueous and organic environments. Addressing solubility issues associated with poorly water-soluble drugs has largely resolved the need to enhance drug absorption and bioavailability. As mucosal formulations and topical administration progress in the future, nanosuspension drug delivery, straightforward formulation techniques, and versatile applications will continue to be subjects of interest. Nanosuspensions have undergone extensive scrutiny in preparation for topical applications, encompassing ocular, pulmonary, and dermal usage. Among the numerous methods aimed at improving cutaneous application, nanocrystals represent a relatively recent yet profoundly intriguing approach. Despite the increasing availability of various nanosuspension products, primarily designed for oral administration, only a limited number of studies have explored skin permeability and drug accumulation in the context of nanosuspensions. Nevertheless, the scant published research unequivocally underscores the potential of this approach for enhancing cutaneous bioavailability, particularly for active ingredients with low to medium solubility. Nanocrystals exhibit increased skin adhesiveness in addition to heightened saturation solubility and dissolution rate, thereby augmenting cutaneous distribution. The article provides a comprehensive overview of nanosuspensions for topical application. The methodology employed is robust, with a well-defined experimental design; however, the limited sample size raises concerns about the generalizability of the findings. While the results demonstrate promising outcomes in terms of enhanced drug delivery, the discussion falls short of addressing certain limitations. Additionally, the references largely focus on recent studies, but a more diverse inclusion of historical perspectives could offer a more holistic view of the subject.

Preparation and in Vitro Characterization of Fatty-Acid Modified Pirarubicin Nanosuspensions Stabilized by Albumin.

Pirarubicin (THP) shows more rapid intracellular uptake, more effective antitumor activity, and less cardiac toxicity, compared to doxorubicin. However, THP is distributed to both tumor and normal tissues indiscriminately. This study aimed to develop a nanosuspension to deliver THP to tumor tissues more efficiently. Fatty-acid-modified THPs (FA-THPs; octanoic acid, dodecanoic acid, palmitic acid-THPs) were synthesized to increase the hydrophobicity of THP. Nanosuspensions of these FA-THPs were then prepared using an antisolvent precipitation technique. Among the FA-THPs, the most efficiently drug-loaded nanosuspension was obtained from palmitic acid-THP (pal-THP) using an aqueous antisolvent containing bovine serum albumin as a stabilizer. The pal-THP nanoparticles in the nanosuspension were confirmed to be of optimal size (100-125 nm) for delivery to tumor tissues using dynamic light scattering and transmission electron microscopy. The pal-THP nanosuspension showed cytotoxicity in colon 26 cells. The nanosuspension was shown to disintegrate in the presence of surfactants such as lecithin, liberating pal-THP, which was converted to free THP in acidic media. It is therefore proposed that pal-THP nanoparticles that reach tumor cells after intravenous administration would exert antitumor effect by liberating pal-THP (i.e., disintegration of nanoparticles by the interaction with cell membrane), followed by the release of free THP in the acidic milieu of tumor cells. These findings indicate that FA-THP nanosuspensions, particularly pal-THP nanosuspension, hold promise as a candidate for cancer treatment. However, further in vivo studies are necessary.

Preparation and Comprehensive Evaluation of the Efficacy and Safety of Chlorantraniliprole Nanosuspension.

Chlorantraniliprole is a broad-spectrum insecticide that has been widely used to control pests in rice fields. Limited by its low solubility in both water and organic solvents, the development of highly efficient and environmentally friendly chlorantraniliprole formulations remains challenging. In this study, a low-cost and scalable wet media milling technique was successfully employed to prepare a chlorantraniliprole nanosuspension. The average particle size of the extremely stable nanosuspension was 56 nm. Compared to a commercial suspension concentrate (SC), the nanosuspension exhibited superior dispersibility, as well as superior foliar wetting and retention performances, which further enhanced its bioavailability against Cnaphalocrocis medinalis. The nanosuspension dosage could be reduced by about 40% while maintaining a comparable efficacy to that of the SC. In addition, the chlorantraniliprole nanosuspension showed lower residual properties, a lower toxicity to non-target zebrafish, and a smaller effect on rice quality, which is conducive to improving food safety and the ecological safety of pesticide formulations. In this work, a novel pesticide-reduction strategy is proposed, and theoretical and data-based support is provided for the efficient and safe application of nanopesticides.

Long-term antitrypanosomal effect of quinapyramine sulphate-loaded oil-based nanosuspension in T. evansi-infected mouse model.

The goal of the present work consisted of the formulation development and evaluation of quinapyramine sulphate (QS)-loaded long-acting oil-based nanosuspension for improved antitrypanosomal effect. QS was transformed into a hydrophobic ionic complex using anionic sodium cholate (Na.C). The complex was characterized by FTIR, DSC, and XRD. Oil-based nanosuspension was prepared by dispersing the QS-Na.C complex in thixotropically thickened olive oil. The nanoformulation was found to be cytocompatible (82.5 ± 5.87% cell viability at the minimum effective concentration [MEC]) in THP-1 cell lines and selectively trypanotoxic (p < 0.0001). The pharmacokinetic studies of QS-Na.C complex-loaded oily nanosuspension showed 13.54-fold, 7.09-fold, 1.78-fold, and 17.35-fold increases in t1/2, AUC0-∞, Vz/F, and MRT0-ꝏ, respectively, as compared to free QS. Moreover, a 7.08-fold reduction in plasma clearance was observed after the treatment with the optimized formulation in Wistar rats. Furthermore, treatment with QS-Na.C complex-loaded oily nanosuspension (7.5 mg/kg) in T. evansi-infected mice model showed the absence of parasitaemia for more than 75 days after the treatment during in vivo efficacy studies. The efficacy of the treatment was assessed by observation of blood smear and PCR assay for DNA amplification. To conclude, our findings suggest that the efficient delivery of QS from the developed QS-Na.C complex-loaded oily nanosuspension could be a promising treatment option for veterinary infections against trypanosomiasis.

Impact of defibrillation technique on the rheological, thermo-mechanical, and nutritional properties of nanosuspensions produced from multiple fractions of pinhão seed (Araucaria angustifolia (Bertol.) Kuntze).

This work aimed to evaluate the influence of the mechanical defibrillation technique on the pinhão nanosuspensions production obtained from the whole pinhão, its coat, and almond. The nanosuspensions were characterized concerning their composition, morphology, thermal stability, rheological behavior, compound profiling, and cytotoxicity. The results revealed a significant fiber content in pinhão coat nanosuspension (63.12 ± 0.52 %) and non-fiber carbohydrates in whole pinhão (59.00 ± 0.13 %) and almond (74.39 ± 0.23 %) nanosuspensions. The defibrillation process led to micro/nano-sized fibers in pinhão coat nanosuspensions and small-size starch granules in almond nanosuspensions. The nanosuspensions containing pinhão coat exhibited a gel-like behavior, while almond nanosuspensions displayed liquid-like characteristics. Pinhão coat nanosuspensions presented a significant content of flavonoids and phytosterols, whereas almond-based nanosuspensions contained substantial sugar amounts. No cytotoxicity was observed at the concentrations evaluated. These findings demonstrated that the defibrillation technique impacted the properties of pinhão constituents, allowing their application in new product development.

In vivo Pharmacokinetic Analysis of Shenbai Nanosuspension in Rats Based on Overall Composition of Chinese Materia Medica / 中国实验方剂学杂志

ObjectiveTo clarify the scientific validity of in vivo pharmacokinetic determination of the whole drug composition in Shenbai nanosuspension in rats， and to provide methodological guidance and theoretical basis for the in vivo study of multi-component complex system of traditional Chinese medicine（TCM） preparations. MethodThe concentration of the overall components， mainly total saponins and total polysaccharides in Shenbai decoction and Shenbai nanosuspension， was determined in rat plasma at different times by area under the absorbance-wavelength curve method（AUAWC）， and the concentration of individual ginsenoside Rg1 was determined by high performance liquid chromatography（HPLC）， and the methodology was verified. The pharmacokinetic parameters of the whole component were compared with those of ginsenoside Rg1 to evaluate the in vivo operational characteristics of the two preparations. ResultThe methodological investigations of AUAWC and HPLC were in accordance with the requirements. AUAWC analysis showed that the overall components in both the decoction group and the nanosuspension group showed a one-compartment model， with half-life（t1/2） of 2.43 h and 2.04 h， respectively. The relative bioavailability of Shenbai nanosuspension was 138.99%. HPLC assay showed that ginsenoside Rg1 in the decoction group and the nanosuspension group showed a two-compartment model， with distribution half-life（t1/2α） of 0.13 h and 2.55 h， and elimination half-life（t1/2β） were 14.28 h and 3.85 h， respectively. The relative bioavailability of Shenbai nanosuspension was 127.49%. Compared with Shenbai decoction， the time to peak（tmax）， peak concentration（Cmax） and area under the drug-time curve（AUC） of the overall components and ginsenoside Rg1 in Shenbai nanosuspension were increased. ConclusionThe established AUAWC can be used for the pharmacokinetic study of the overall components of TCM preparations， which is complementary to the results of individual components measured by HPLC， and can provide useful reference for the in vivo study of new dosage forms of TCM.

Roles of Fatty Acid Chain Length and Enzyme-Oriented Drug Controlled Release from pH-Triggering Self-Assembled Fatty Acid Conjugated Quetiapine Nanosuspensions.

Background: Quetiapine (QTP) is a first-line antipsychotic drug, but its therapeutic druggability and patient adherence were limited due to high oral dose strength, low bioavailability and physicochemical/biopharmaceutical issues. Purpose: To investigate the roles of fatty acid chain length and enzyme-oriented QTP controlled release from pH-triggering self-assembled fatty acid conjugated QTP nanosuspensions (NSPs). Methods: QTP was conjugated with different chain length fatty acids (C10-decanoic acid, C14-myristic acid, C18-stearic acid) to obtain QTP-fatty acid conjugates (QFCs: QD, QM, QS) by exploiting 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/4-dimethylaminopyridine (EDC/DMAP) conjugation chemistry. Then, the solubility, partitioning coefficient (log P), cell viability and cleavage kinetics of QFCs were evaluated. The pH-triggering self-assembled behaviors of QFCs to form QTP-fatty acid NSPs (QDN, QMN, QSN) by varying pH, QFC concentration and proton-to-QTP ratios were characterized. The morphological images, critical micelle concentration (CMC), physicochemical properties and enzyme-oriented QTP controlled release of NSPs were examined. Results: Three QFCs were synthesized with different chain length fatty acids from QTP after desalting fumarate from QTP fumarate. The pH, QFC concentration and proton-to-quetiapine molar ratio could influence physicochemical properties and nanonization behaviors of QFCs. All three QFCs showed no effect on the viability of myoblast cells. The pH-triggering self-assembly of amphiphilic QFCs to form nanoparticles (NPs) occurred as the amine moiety of QTP was readily ionized in a strongly acidic environment (pH 1.2). Interestingly, the longer the fatty acid chain length, the lower water solubility, the higher log P (lipophilicity) and the smaller NP particle size were observed. The conversion rate of QFCs to liberate QTP by esterase in human plasma and liver S9 fractions was also inversely proportional to the fatty acid carbon chain length. Interestingly, the freeze-dried QMN showed the esterase-oriented controlled release of QTP over one month, unlike the initial burst release of QDN or the slowly delayed release pattern of QSN. Conclusion: A new pH-triggering self-assembled nanonization platform was developed using different chain length fatty acid conjugated QTP in low pH environment. By varying fatty acid chain length, the enzyme-oriented QTP controlled release dosage form was challenged to enhance the therapeutic effectiveness of QTP.