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The main issues with local delivery of cosmetics are their high sensitivity and limited drug loading of active pharmaceutical ingredient. Nanocrystal technology offers consumers cutting-edge and effective products and exhibits enormous development potential in the beauty business as a new delivery method to address the issue of low solubility and low permeability of sensitive chemicals. In this review, we described the processes for making NCs, along with the impacts of loading and the uses of different carriers. Among them, nanocrystalline loaded gel and emulsion are widely used and may further improve the stability of the system. Then, we introduced the beauty efficacy of drug NCs from five aspects: anti-inflammation and acne, anti-bacterial, lightening and freckle removal, anti-aging as well as UV protection. Following that, we presented the current scenario about stability and safety. Finally, the challenges and vacancy were discussed along with the potential uses of NCs in the cosmetics industry. This review serves as a resource for the advancement of nanocrystal technology in the cosmetics sector., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests Xiaoqing Miao reports financial support were provided by Institute of Geology and Geophysics Chinese Academy of Sciences., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Nanocrystals are characterized by high drug loading, low carrier toxicity, and great structural stability. Therefore, they are a promising and versatile strategy for enhancing the local delivery of insoluble drugs. They achieve this by improving skin adhesion, concentration gradients, and hair follicle accumulation, as well as generating corona diffusion (which forms through the overlap of dissolved drug molecules around a nanocrystal). The development of suitable formulations for enhancing the passive diffusion and/or follicular targeting of nanocrystals is of great importance to clinical practice. We sought to elucidate the influence of particle size, a penetration enhancer, and delivery vehicles on the follicular accumulation and passive dermal permeation of nanocrystals. For this purpose, curcumin nanocrystals (particle size: 60, 120, and 480 nm) were incorporated into xanthan gum gels (delivery vehicles) with propylene glycol (penetration enhancer). This evaluation was performed in a porcine skin model. The results showed that xanthan gum reduced the follicular penetration and passive skin accumulation of curcumin nanocrystals. The propylene glycol enhanced the skin penetration and retention of curcumin nanocrystals in vitro for 24 h. The curcumin nanocrystals of smaller particle size (i.e., 60 and 120 nm) displayed higher passive skin penetration versus those with larger particle size (i.e., 480 nm); however, the latter type showed deeper follicular accumulation. In conclusion, the delivery vehicles, penetration enhancer, and particle sizes examined in this study affect the dermal penetration and accumulation of curcumin nanocrystals. Hence, their effects should be adequately considered when designing formulations of such nanocrystals., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Topical drug delivery methods are important in the treatment of skin diseases. Drug nanocrystals, which are nanometersized particles of active pharmaceutical ingredients, offer efficient topical delivery with high stability, high drug loading capacity, steady dissolution, and sustained drug release profiles. The use of nanocrystals for the topical delivery of skin disease therapies is currently being evaluated; this review focuses on how nanocrystals facilitate active pharmaceutical ingredient transport across skin barriers, exploring the underlying transportation mechanisms of the nanocrystals and active pharmaceutical ingredient molecules to the dermal and epidermal skin cells. In topical delivery, previous skin treatments, choice of excipients and vehicles, and penetration enhancement strategies critically influence the topical delivery of drug nanocrystals. Various research and applications of drug nanocrystals in skin disease therapy are highlighted in this review, and intellectual property protection for drug nanocrystal formulations, clinical trial data, and products with commercial potential are also discussed.

Drug nanocrystals (NCs) with fascinating physicochemical properties have attracted great attention in drug delivery. High drug-loading efficiency, great structural stability, steady dissolution, and long circulation time are a few examples of these properties, which makes drug NCs an excellent formulation for efficient cancer therapy. In the last two decades, there are a lot of hydrophobic or lipophilic drugs, such as paclitaxel (PTX), camptothecin (CPT), thymectacin, busulfan, cyclosporin A, 2-devinyl-2-(1-hexyloxyethyl) pyropheophorbide (HPPH), and so on, which have been formulated into drug NCs for cancer therapy. In this review, we summarized the recent advances in drug NCs-based cancer treatment. So far, there are main three methods to synthesize drug NCs, including top-down, bottom-up, and combination methods. The characterization methods of drug NCs were also elaborated. Furthermore, the applications and mechanisms of drug NCs were introduced by their administration routes. At the end, we gave a brief conclusion and discussed the future perspectives of drug NCs in cancer therapy. This article is categorized under: Implantable Materials and Surgical Technologies > Nanomaterials and Implants Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology., (© 2017 Wiley Periodicals, Inc.)

With the wide application of nanotechnology to drug delivery systems, a simple, dynamic and visual in vivo model for high-throughput screening of novel formulations with fluorescence markers across biological barriers is desperately needed. In vitro cell culture models have been widely used, although they are far from a complimentary in vivo system. Mammalian animal models are common predictive models to study transport, but they are costly and time consuming. Zebrafish (Danio rerio), a small vertebrate model, have the potential to be developed as an "intermediate" model for quick evaluations. Based on our previously established coumarin 6 nanocrystals (C6-NCs), which have two different sizes, the present study investigates the transportation of C6-NCs across four biological barriers, including the chorion, blood brain barrier (BBB), blood retinal barrier (BRB) and gastrointestinal (GI) barrier, using zebrafish embryos and larvae as in vivo models. The biodistribution and elimination of C6 from different organs were quantified in adult zebrafish. The results showed that compared to 200nm C6-NCs, 70nm C6-NCs showed better permeability across these biological barriers. A FRET study suggested that intact C6-NCs together with the free dissolved form of C6 were absorbed into the larval zebrafish. More C6 was accumulated in different organs after incubation with small sized NCs via lipid raft-mediated endocytosis in adult zebrafish, which is consistent with the findings from in vitro cell monolayers and the zebrafish larvae model. C6-NCs could be gradually eliminated in each organ over time. This study demonstrated the successful application of zebrafish as a simple and dynamic model to simultaneously assess the transport of nanosized drug delivery systems across several biological barriers and biodistribution in different organs, especially in the brain, which could be used for central nervous system (CNS) drug and delivery system screening., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Nanocrystals (NCs) were utilized as oral formulations in commercial products to deliver lipophilic drug, but their transport mechanisms are not fully understood. This study aimed to explore the transport mechanism of NCs using in vitro Madin-Darby canine kidney II (MDCK II) cells and in vivo larval zebrafish models. Coumarin 6 (C6) was formulated into NCs with particle size of 67.5 ± 5.2 and 190 ± 9.2 nm. In vitro studies showed that 70 nm NCs accumulated in lysosome and endoplasmic reticulum (ER) as destinations. Lipid raft pathways mediated the endocytosis, while lipid raft, ER/Golgi, and Golgi/plasma membrane pathways were involved in exocytosis and transcytosis process. However, 200 nm NCs accumulated more in a lysosome, where lipid raft pathways were also involved in the endocytosis process. In vivo studies in larval zebrafish model further confirmed that the above network plays an important role in the absorption and distribution of C6-NCs.

The aim of this study was to fabricate 20(S)-protopanaxadiol (PPD) nanocrystals to improve PPD's oral bioavailability and brain delivery. PPD nanocrystals were fabricated using an anti-solvent precipitation approach where d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) was optimized as the stabilizer. The fabricated nanocrystals were nearly spherical with a particle size and drug loading of 90.44 ± 1.45 nm and 76.92%, respectively. They are in the crystalline state and stable at 4°C for at least 1 month. More than 90% of the PPD could be rapidly released from the nanocrystals, which was much faster than the physical mixture and PPD powder. PPD nanocrystals demonstrated comparable permeability to solution at 2.52 ± 0.44×10(-5)cm/s on MDCK monolayers. After oral administration of PPD nanocrystals to rats, PPD was absorbed quickly into the plasma and brain with significantly higher Cmax and AUC0-t compared to those of the physical mixture. However, no brain targeting was observed, as the ratios of the plasma AUC0-t to brain AUC0-t for the two groups were similar. In summary, PPD nanocrystals are a potential oral delivery system to improve PPD's poor bioavailability and its delivery into the brain for neurodegenerative disease and intracranial tumor therapies in the future., (Copyright © 2015 Elsevier B.V. All rights reserved.)

A surprisingly large proportion of new chemical entities (NCE) is emerging from the drug discovery pipeline, and many active components extracted from herbal medicines are water insoluble, which represents a great challenge for their development. Nanosuspensions, which are submicron colloidal dispersions of pure drug particles that are stabilised by a small percentage of the excipients, could dramatically enhance the saturated solubility, dissolution rate and adhesion of drug particles to cell membranes. Nanosuspensions are the most suitable for drugs that require high dosing or have limited administrative volume. After 20 years of development, several oral products and one injectable product are commercially available. The aim of this review is to fill the gap between rational formulation designs and the in vivo performance of poorly water-soluble drug nanosuspensions. Specifically, this review will correlate characteristics of nanosuspension formulations, including drug property, particle size, crystallinity, stabiliser and surface property, with their transport, pharmacokinetics, bioactivity and toxicity after delivery by different administration routes. The elucidation of the mechanisms of targeted drug delivery, cellular transport and internalisation of nanosuspensions are also reviewed to interpret the in vivo performance of these nanosuspensions. Moreover, the recent application of nanosuspensions for poorly water-soluble herbal medicines is highlighted.

Epimedium-derived flavonoid glycosides are widely used for the prevention of osteoporosis, but these compounds generally exhibit poor membrane permeability and oral absorption. To address these limitations, the bioactive lipophilic aglycone icaritin (ICT) was selected and successfully developed into nanocrystals (ICTN) through the antisolvent-precipitation method. After the parameters in the preparation of ICTN were optimized, the morphology, crystallinity, adsorption of the stabilizers on the ICT surface, and the dissolution of the resulting nanocrystals were characterized. The pharmacokinetics in rat and the in vitro antiosteoporosis activity of serum withdrawn after the oral administration of ICTN to rats on mouse osteoblastic cells were evaluated. Consistent with its good performance in stabilizing the ICT nanosuspension, atomic force microscopy showed that hydroxypropyl methylcellulose (HPMC) exhibits better adsorption on the ICT surface compared with other stabilizers. Needle-shaped crystals (∼ 220 nm in diameter) with a high drug loading (∼ 90%) were generated when 0.16 mL of the ICT acetone solution (10 mg/mL) was injected quickly into 2 mL of the HPMC solution (0.02%, w/w) under ultrasonication for 10 s at room temperature. The thermal analysis demonstrated that the majority of the particles are in their crystalline forms, similarly to the unformulated ICT. After oral administration, ICTN exhibited a faster dissolution rate and significantly faster absorption, as supported by the increased AUC0-36h and Cmax and the reduced Tmax of these nanocrystals compared with the raw suspension (p < 0.05). Compared with blank serum, enhanced proliferation and differentiation activities were observed when serum withdrawn after the oral administration of ICTN in rat was incubated with osteoblast MC3T3-E1 cells. The present delivery system could provide a new promising strategy for BCS IV glycoside of flavonoids or other natural products by formulation of their bioactive lipophilic aglycone forms to enhance oral absorption and in vivo bioactivity.

Purpose: The aim of this study was to develop cilostazol (CLT) nanocrystals intended to improve its dissolution rate and enhance its bioavailability., Methods: In this study, CLT nanosuspension was prepared by the anti-solvent and high-pressure homogenization method. The effects of the production parameters, such as the stabilizer concentration, pressure and number of cycles, were investigated. Characterization of the product was performed by scanning electron microscopy (SEM), Nitrogen adsorption, differential scanning calorimetry (DSC), X-ray powder diffraction analysis (XRPD), X-ray Photoelectron Spectroscopy (XPS), particle size analysis and dissolution testing. Additionally, the comparison studies of oral bioavailability in beagle dogs of three type tables were performed., Results: The images of SEM showed a spherical smooth CLT powder, and Nitrogen adsorption test revealed spray dried powder were porous with high BET surface area compared with that of raw CLT. DSC and XRPD results demonstrated that the combination of preferred polymorph B and C of CLT were prepared successfully, the saturation solubility of the nanosized crystalline powder is about 5 fold greater than that of raw CLT, and the dissolution rate was enhanced 4 fold than that of raw CLT. The Cmax and AUC0-48h of CLT nanosized crystalline tablets were 2.1 fold and 1.9 fold, and 3.0 fold and 2.3 fold compared with those of the nanosized tablets and commercial tablets, respectively., Conclusion: The anti-solvent-high-pressure homogenization technique was employed successfully to produce cilostazol nanosuspensions. The bioavailability of CLT tablets prepared using spray dried nanosized crystalline powder after oral administration to dogs was markedly increased compared with that produced by nanosized tablets and commercial tablets, because of its greater dissolution rate owing to its transition of the crystalline state to form C and form B, reduced particle size and porous structure with increased surface area.