Nano-Hydroxyapatite/PLGA Mixed Scaffolds as a Tool for Drug Development and to Study Metastatic Prostate Cancer in the Bone.

(1) Background: Three-dimensional (3D) in vitro, biorelevant culture models that recapitulate cancer progression can help elucidate physio-pathological disease cues and enhance the screening of more effective therapies. Insufficient research has been conducted to generate in vitro 3D models to replicate the spread of prostate cancer to the bone, a key metastatic site of the disease, and to understand the interplay between the key cell players. In this study, we aim to investigate PLGA and nano-hydroxyapatite (nHA)/PLGA mixed scaffolds as a predictive preclinical tool to study metastatic prostate cancer (mPC) in the bone and reduce the gap that exists with traditional 2D cultures. (2) Methods: nHA/PLGA mixed scaffolds were produced by electrospraying, compacting, and foaming PLGA polymer microparticles, +/- nano-hydroxyapatite (nHA), and a salt porogen to produce 3D, porous scaffolds. Physicochemical scaffold characterisation together with an evaluation of osteoblastic (hFOB 1.19) and mPC (PC-3) cell behaviour (RT-qPCR, viability, and differentiation) in mono- and co-culture, was undertaken. (3) Results: The results show that the addition of nHA, particularly at the higher-level impacted scaffolds in terms of mechanical and degradation behaviour. The nHA 4 mg resulted in weaker scaffolds, but cell viability increased. Qualitatively, fluorescent imaging of cultures showed an increase in PC-3 cells compared to osteoblasts despite lower initial PC-3 seeding densities. Osteoblast monocultures, in general, caused an upregulation (or at least equivalent to controls) in gene production, which was highest in plain scaffolds and decreased with increases in nHA. Additionally, the genes were downregulated in PC3 and co-cultures. Further, drug toxicity tests demonstrated a significant effect in 2D and 3D co-cultures. (4) Conclusions: The results demonstrate that culture conditions and environment (2D versus 3D, monoculture versus co-culture) and scaffold composition all impact cell behaviour and model development.

Modelling acute myeloid leukemia (AML): What's new? A transition from the classical to the modern.

Acute myeloid leukemia (AML) is a heterogeneous malignancy affecting myeloid cells in the bone marrow (BM) but can spread giving rise to impaired hematopoiesis. AML incidence increases with age and is associated with poor prognostic outcomes. There has been a disconnect between the success of novel drug compounds observed in preclinical studies of hematological malignancy and less than exceptional therapeutic responses in clinical trials. This review aims to provide a state-of-the-art overview on the different preclinical models of AML available to expand insights into disease pathology and as preclinical screening tools. Deciphering the complex physiological and pathological processes and developing predictive preclinical models are key to understanding disease progression and fundamental in the development and testing of new effective drug treatments. Standard scaffold-free suspension models fail to recapitulate the complex environment where AML occurs. To this end, we review advances in scaffold/matrix-based 3D models and outline the most recent advances in on-chip technology. We also provide an overview of clinically relevant animal models and review the expanding use of patient-derived samples, which offer the prospect to create more "patient specific" screening tools either in the guise of 3D matrix models, microphysiological "organ-on-chip" tools or xenograft models and discuss representative examples.

Incorporation in Lipid Microparticles of Acid Red 87, a Colorant Used in Tattoo Inks: Effect on Photodegradation Under Simulated Sunlight and Laser Radiation.

Tattoo colorants decompose under solar radiation and when exposed to laser light for their removal, leading to the accumulation in the dermis of toxic products. Aim of this study was to develop lipid microparticles (LMs) loaded with the colorant, Acid Red 87 (C.I. 45380) used in tattoo inks, and to investigate the effect of this system on the photostability of the colorant under simulated sunlight or laser irradiation. LMs loaded with C.I. 45380 were prepared by melt emulsification using tristearin and phosphatidylcholine as excipients. They were characterized by optical microscopy, laser diffraction, X-ray diffraction and release studies. Free C.I. 45380 and the colorant-loaded LMs were irradiated with a solar simulator or a Q-switched laser. Irradiation with a solar simulator demonstrated that photodecomposition of C.I. 45380 was markedly reduced by incorporation of the dye in the LMs, from 20.5 ± 4.6% to 1.3 ± 1.8%. Conversely, the laser-induced degradation of the colorant (30.1 ± 6.6%) was not significantly influenced by encapsulation in the LMs (the encapsulated C.I. 45380 loss was 27.4 ± 5.5%). Incorporation of C.I. 45380 in lipid microparticles enhances the photostability under sunlight of tattoo inks containing this colorant, without affecting its laser-induced degradation and hence laser removal efficiency.

Glyceryl Tristearate-Based Lipid Microparticles Loaded with the Tattoo Colorant, Acid Red 87: Colorant Retention Capacity in Excised Porcine Skin.

BACKGROUND: With the increasing diffusion of tattooing, the photolability of tattoo inks has become a critical issue, as available data indicated that several tattoo colorants are unstable under sunlight, generating potentially toxic photodegradation products. Therefore, it is desirable to enhance the photostability of coloring agents contained in tattoo inks. AIMS: Lipid microparticles (LMs) highly loaded with Acid Red 87 (C.I. 45380), a colorant used in tattoo inks, were evaluated for their effect on the colorant photoinstability. In addition, the capacity of the LMs to retain the incorporated C.I. 45380 colorant after their intradermal administration in excised porcine skin was investigated. METHODS: LMs loaded with C.I. 45380 were prepared using glyceryl tristearate as the lipidic material and phosphatidylcholine as the surfactant. Non-encapsulated C.I. 45380 or the colorant-loaded LMs were irradiated with a solar simulator for photodecomposition studies or introduced in the excised porcine skin mounted in Franz diffusion cells for stability evaluation in the dermal tissue. RESULTS AND CONCLUSION: The colorant content of the microparticles was 17.7%, and their size ranged from 25 to 170 µm. The light-induced degradation of C.I. 45380 was significantly decreased by its incorporation in the LMs from 20.2 ± 5.8% to 1.9 ± 2.1%. Moreover, after intradermal injection of free or microencapsulated C.I. 45380 in the excised pig skin, the LMs reduced by 93.7% (from 24.6 to 1.5%) the quantity of the colorant diffused and hence lost in the Franz cell receptor fluid. Hence, the LM carrier efficiently retained the entrapped C.I. 45380 following incubation in the dermal region of the isolated porcine skin, which is in favor of a long-lasting tattoo. Based on these data, the incorporation of C.I. 45380 in the LMs could represent a potentially useful strategy to reduce the photodecomposition of the tattoo colorant and its harmful interactions with the skin tissue.