Microfluidic nanoparticle synthesis for oral solid dosage forms: A step toward clinical transition processes.

Nanomedicine provides various opportunities for addressing medical challenges associated with drug bioavailability, stability, and efficacy. In particular, oral nanoparticles (NPs) represent an alternative strategy to enhance the solubility and stability of active ingredients through the gastrointestinal tract. The nanocarriers could be used for both local and systemic targeting, enabling controlled release of encapsulated drugs. This approach allows more efficient therapies. In this work, we aim to develop reliable oral solid dosage forms incorporating NPs produced by either one pot synthesis or continuous production, following protocols that yield highly consistent outcomes, promoting their technology transfer and clinical use. Microfluidics technology was selected to allow an automated and highly productive synthetic approach suitable for the highly throughput production. In particular, innovative systems, which combine advantage of NPs and solid dosage formulation, were designed, developed, and characterized demonstrating the possibility to obtaining oral administration. The resulting NPs were thus carried on oral dosage forms, i.e., pellets and minitablets. NPs resulted stable after dosage forms manufacturing, leading to confidence also on protection of encapsulated drugs. Indomethacin was used as a tracer to test biopharmaceutical behaviour. Anti-inflammatories or cytotoxic chemotherapeutics could be vehiculated leading to a breakthrough in the treatment of severe diseases allowing the oral administration of these drugs. We believe that the advancement achieved with the results of our work paves the way for the progression of nanoproducts into clinical transition processes.

Co-processed materials testing as excipients to produce Orally Disintegrating Tablets (ODT) using binder jet 3D-printing technology.

The use of co-processed materials for Orally Disintegrating Tablets (ODT) preparation by direct compression is well consolidated. However, the evaluation of their potential for ODT preparation by 3D printing technology remains almost unexplored. The present study aimed to estimate the use of commercially available co-processed excipients, conventionally applied in compression protocols, for the preparation of ODTs with binder jetting-3D printing technology. The latter was selected among the 3D printing techniques because the deposition of multiple powder layers allows for obtaining highly porous and easily disintegrating dosage forms. The influence of some process parameters, including layer thickness, type of waveform and spread speed, on the physical and mechanical properties of the prototypes printed were evaluated. Our results suggested that binder jetting-3D printing technology could benefit from the co-processed excipients for the preparation of solid dosage forms. The process optimization conducted with the experiments reported in this work indicated that additional excipients were needed to improve the physical properties of the resulting ODTs.

Folic acid functionalization for targeting self-assembled paclitaxel-based nanoparticles.

Hetero-nanoparticles self-assembled from a conjugate bearing folic acid as the targeting agent, and another bearing paclitaxel as the active agent are reported. Hetero-nanoparticles containing varying percentages of folic acid conjugates are characterised, and their biological activity is determined.

Surfactant protein D (SP-D) as a biomarker of SARS-CoV-2 infection.

BACKGROUND: Surfactant protein-D (SP-D) is a lung-resident protein that has emerged as a potential biomarker for COVID-19. Previous investigations on acute respiratory distress syndrome patients demonstrated a significant increment of SP-D serum levels in pathological conditions. Since SP-D is not physiologically permeable to alveoli-capillary membrane and poorly expressed by other tissues, this enhancement is likely due to an impairment of the pulmonary barrier caused by prolonged inflammation. METHODS: A retrospective study on a relatively large cohort of patients of Hospital Pio XI of Desio was conducted to assess differences of the hematic SP-D concentrations among COVID-19 patients and healthy donors and if SP-D levels resulted a risk factor for disease severity and mortality. RESULTS: The first analysis, using an ANOVA-model, showed a significant difference in the mean of log SP-D levels between COVID-19 patients and healthy donors. Significant variations were also found between dead vs survived patients. Results confirm that SP-D concentrations were significantly higher for both hospitalized COVID-19 and dead patients, with threshold values of 150 and 250 ng/mL, respectively. Further analysis conducted with Logistic Mixed models, highlighted that higher SP-D levels at admission and increasing differences among follow-up and admission values resulted the strongest significant risk factors of mortality (model predictive accuracy, AUC = 0.844). CONCLUSIONS: The results indicate that SP-D can be a predictive marker of COVID-19 disease and its outcome. Considering its prognostic value in terms of mortality, the early detection of SP-D levels and its follow-up in hospitalized patients should be considered to direct the therapeutic intervention.

Conjugation of gold nanoparticles with multidentate surfactants for enhanced stability and biological properties.

This work originated from the need to functionalize surfactant-coated inorganic nanoparticles for biomedical applications, a process that is limited by excess unbound surfactant. These limitations are connected to the bioconjugation of targeting molecules that are often in equilibrium between the free aliquot in solution and that which binds the surface of the nanoparticles. The excess in solution can play a role in the biocompatability in vitro and in vivo of the final nanoparticles stock. For this purpose, we tested the ability of common surfactants - monothiolated polyethylene glycol and amphiphilic polymers - to colloidally stabilize nanoparticles as excess surfactant is removed and compared them to newly appearing multidentate surfactants endowed with high avidity for inorganic nanoparticles. Our results showed that monothiolated polyethylene glycol or amphiphilic polymers have an insufficient affinity to the nanoparticles and as the excess surfactant is removed the colloidal stability is lost, while multidentate high-avidity surfactants excel in the same regard, possibly allowing improvement in an array of nanoparticle applications, especially in those stated.

Specific immunosuppressive role of nanodrugs targeting calcineurin in innate myeloid cells.

Calcineurin (CN) inhibitors currently used to avoid transplant rejection block the activation of adaptive immune responses but also prevent the development of tolerance toward the graft, by directly inhibiting T cells. CN, through the transcription factors of the NFAT family, plays an important role also in the differentiation dendritic cells (DCs), the main cells responsible for the activation of T lymphocytes. Therefore, we hypothesized that the inhibition of CN only in DCs and not in T cells could be sufficient to prevent T cell responses, while allowing for the development of tolerance. Here, we show that inhibition of CN/NFAT pathway in innate myeloid cells, using a new nanoconjugate capable of selectively targeting phagocytes in vivo, protects against graft rejection and induces a longer graft acceptance compared to common CN inhibitors. We propose a new generation of nanoparticles-based selective immune suppressive agents for a better control of transplant acceptance.

Saporin Toxin Delivered by Engineered Colloidal Nanoparticles Is Strongly Effective against Cancer Cells.

Ribosome-inactivating proteins, including Saporin toxin, have found application in the search for innovative alternative cancer therapies to conventional chemo- and radiotherapy. Saporin's main mechanism of action involves the inhibition of cytoplasmic protein synthesis. Its strong theoretical efficacy is counterbalanced by negligible cell uptake and diffusion into the cytosol. In this work, we demonstrate that by immobilizing Saporin on iron oxide nanoparticles coated with an amphiphilic polymer, which promotes nanoconjugate endosomal escape, a strong cytotoxic effect mediated by ribosomal functional inactivation can be achieved. Cancer cell death was mediated by apoptosis dependent on nanoparticle concentration but independent of surface ligand density. The cytotoxic activity of Saporin-conjugated colloidal nanoparticles proved to be selective against three different cancer cell lines in comparison with healthy fibroblasts.

Development of an Effective Tumor-Targeted Contrast Agent for Magnetic Resonance Imaging Based on Mn/H-Ferritin Nanocomplexes.

Magnetic resonance imaging (MRI) is one of the most sophisticated diagnostic tools that is routinely used in clinical practice. Contrast agents (CAs) are commonly exploited to afford much clearer images of detectable organs and to reduce the risk of misdiagnosis caused by limited MRI sensitivity. Currently, only a few gadolinium-based CAs are approved for clinical use. Concerns about their toxicity remain, and their administration is approved only under strict controls. Here, we report the synthesis and validation of a manganese-based CA, namely, Mn@HFn-RT. Manganese is an endogenous paramagnetic metal able to produce a positive contrast like gadolinium, but it is thought to result in less toxicity for the human body. Mn ions were efficiently loaded inside the shell of a recombinant H-ferritin (HFn), which is selectively recognized by the majority of human cancer cells through their transferrin receptor 1. Mn@HFn-RT was characterized, showing excellent colloidal stability, superior relaxivity, and a good safety profile. In vitro experiments confirmed the ability of Mn@HFn-RT to efficiently and selectively target breast cancer cells. In vivo, Mn@HFn-RT allowed the direct detection of tumors by positive contrast enhancement in a breast cancer murine model, using very low metal dosages and exhibiting rapid clearance after diagnosis. Hence, Mn@HFn-RT is proposed as a promising CA candidate to be developed for MRI.

Full-Length Recombinant hSP-D Binds and Inhibits SARS-CoV-2.

SARS-CoV-2 infection of host cells is driven by binding of the SARS-CoV-2 spike-(S)-protein to lung type II pneumocytes, followed by virus replication. Surfactant protein SP-D, member of the front-line immune defense of the lungs, binds glycosylated structures on invading pathogens such as viruses to induce their clearance from the lungs. The objective of this study is to measure the pulmonary SP-D levels in COVID-19 patients and demonstrate the activity of SP-D against SARS-CoV-2, opening the possibility of using SP-D as potential therapy for COVID-19 patients. Pulmonary SP-D concentrations were measured in bronchoalveolar lavage samples from patients with corona virus disease 2019 (COVID-19) by anti-SP-D ELISA. Binding assays were performed by ELISAs. Protein bridge and aggregation assays were performed by gel electrophoresis followed by silver staining and band densitometry. Viral replication was evaluated in vitro using epithelial Caco-2 cells. Results indicate that COVID-19 patients (n = 12) show decreased pulmonary levels of SP-D (median = 68.9 ng/mL) when compared to levels reported for healthy controls in literature. Binding assays demonstrate that SP-D binds the SARS-CoV-2 glycosylated spike-(S)-protein of different emerging clinical variants. Binding induces the formation of protein bridges, the critical step of viral aggregation to facilitate its clearance. SP-D inhibits SARS-CoV-2 replication in Caco-2 cells (EC90 = 3.7 µg/mL). Therefore, SP-D recognizes and binds to the spike-(S)-protein of SARS-CoV-2 in vitro, initiates the aggregation, and inhibits viral replication in cells. Combined with the low levels of SP-D observed in COVID-19 patients, these results suggest that SP-D is important in the immune response to SARS-CoV-2 and that rhSP-D supplementation has the potential to be a novel class of anti-viral that will target SARS-CoV-2 infection.

Impact of Tuning the Surface Charge Distribution on Colloidal Iron Oxide Nanoparticle Toxicity Investigated in Caenorhabditis elegans.

Assessing the toxic effect in living organisms remains a major issue for the development of safe nanomedicines and exposure of researchers involved in the synthesis, handling and manipulation of nanoparticles. In this study, we demonstrate that Caenorhabditis elegans could represent an in vivo model alternative to superior mammalians for the collection of several physiological functionality parameters associated to both short-term and long-term effects of colloidally stable nanoparticles even in absence of microbial feeding, usually reported to be necessary to ensure appropriate intake. Contextually, we investigated the impact of surface charge on toxicity of superparamagnetic iron oxide coated with a wrapping polymeric envelop that confers them optimal colloidal stability. By finely tuning the functional group composition of this shallow polymer-obtaining totally anionic, partially pegylated, partially anionic and partially cationic, respectively-we showed that the ideal surface charge organization to optimize safety of colloidal nanoparticles is the one containing both cationic and anionic groups. Our results are in accordance with previous evidence that zwitterionic nanoparticles allow long circulation, favorable distribution in the tumor area and optimal tumor penetration and thus support the hypothesis that zwitterionic iron oxide nanoparticles could be an excellent solution for diagnostic imaging and therapeutic applications in nanooncology.

The emerging role of nanotechnology in skincare.

The role of cosmetic products is rapidly evolving in our society, with their use increasingly seen as an essential contribution to personal wellness. This suggests the necessity of a detailed elucidation of the use of nanoparticles (NPs) in cosmetics. The aim of the present work is to offer a critical and comprehensive review discussing the impact of exploiting nanomaterials in advanced cosmetic formulations, emphasizing the beneficial effects of their extensive use in next-generation products despite a persisting prejudice around the application of nanotechnology in cosmetics. The discussion here includes an interpretation of the data underlying generic information reported on the product labels of formulations already available in the marketplace, information that often lacks details identifying specific components of the product, especially when nanomaterials are employed. The emphasis of this review is mainly focused on skincare because it is believed to be the cosmetics market sector in which the impact of nanotechnology is being seen most significantly. To date, nanotechnology has been demonstrated to improve the performance of cosmetics in a number of different ways: 1) increasing both the entrapment efficiency and dermal penetration of the active ingredient, 2) controlling drug release, 3) enhancing physical stability, 4) improving moisturizing power, and 5) providing better UV protection. Specific attention is paid to the effect of nanoparticles contained in semisolid formulations on skin penetration issues. In light of the emerging concerns about nanoparticle toxicity, an entire section has been devoted to listing detailed examples of nanocosmetic products for which safety has been investigated.

The Role of Polymeric Coatings for a Safe-by-Design Development of Biomedical Gold Nanoparticles Assessed in Zebrafish Embryo.

In the biomedical field, gold nanoparticles (GNPs) have attracted the attention of the scientific community thanks to their high potential in both diagnostic and therapeutic applications. The extensive use of GNPs led researchers to investigate their toxicity, identifying stability, size, shape, and surface charge as key properties determining their impact on biological systems, with possible strategies defined to reduce it according to a Safe-by-Design (SbD) approach. The purpose of the present work was to analyze the toxicity of GNPs of various sizes and with different coating polymers on the developing vertebrate model, zebrafish. In particular, increasing concentrations (from 0.001 to 1 nM) of 6 or 15 nm poly-(isobutylene-alt-maleic anhydride)-graft-dodecyl polymer (PMA)- or polyethylene glycol (PEG)-coated GNPs were tested on zebrafish embryos using the fish embryo test (FET). While GNP@PMA did not exert significant toxicity on zebrafish embryos, GNP@PEG induced a significant inhibition of embryo viability, a delay of hatching (with the smaller size NPs), and a higher incidence of malformations, in terms of tail morphology and eye development. Transmission electron microscope analysis evidenced that the more negatively charged GNP@PMA was sequestered by the positive charges of chorion proteins, with a consequent reduction in the amount of NPs able to reach the developing embryo and exert toxicological activity. The mild toxic response observed on embryos directly exposed to GNP@PMA suggest that these NPs are promising in terms of SbD development of gold-based biomedical nanodevices. On the other hand, the almost neutral GNP@PEG, which did not interact with the chorion surface and was free to cross chorion pores, significantly impacted the developing zebrafish. The present study raises concerns about the safety of PEGylated gold nanoparticles and contributes to the debated issue of the free use of this nanotool in medicine and nano-biotechnologies.

99mTc-Radiolabeled Silica Nanocarriers for Targeted Detection and Treatment of HER2-Positive Breast Cancer.

INTRODUCTION: The overexpression of Human Epidermal Growth Factor Receptor 2 (HER2) is usually associated with aggressive and infiltrating breast cancer (BC) phenotype, and metastases. Functionalized silica-based nanocarriers (SiNPs) can be labeled for in vivo imaging applications and loaded with chemotherapy drugs, making possible the simultaneous noninvasive diagnosis and treatment (theranostic) for HER2-positive BC. METHODS: Firstly, FITC-filled SiNPs, were engineered with two different amounts of Hc-TZ (trastuzumab half-chain) per single nanoparticle (1:2 and 1:8, SiNPs to Hc-TZ ratio), which was 99mTc-radiolabeled at histidine residues for ex vivo and in vivo biodistribution evaluations. Secondly, nanoparticles were loaded with DOX and their in vitro and ex vivo/in vivo delivery was assessed, in comparison with liposomal Doxorubicin (Caelyx). Finally, the treatment efficacy of DOX-SiNPs-TZ (1:8 Hc-TZ) was evaluated in vivo by PET and supported by MS-based proteomics profiling of tumors. RESULTS: SiNPs-TZ (1:8 Hc-TZ) tumor uptake was significantly greater than that of SiNPs-TZ (1:2 Hc-TZ) at 6 hours post-injection (p.i.) in ex vivo biodistribution experiment. At 24 h p.i., radioactivity values remained steady. Fluorescence microscopy, confirmed the presence of radiolabeled SiNPs-TZ (1:8 Hc-TZ) within tumor even at later times. SiNPs-TZ (1:8 Hc-TZ) nanoparticles loaded with Doxorubicin (DOX-SiNPs-TZ) showed a similar DOX delivery capability than Caelyx (at 6 h p.i.), in in vitro and ex vivo assays. Nevertheless, at the end of treatment, tumor volume was significantly reduced by DOX-SiNPs-TZ (1:8 Hc-TZ), compared to Caelyx and DOX-SiNPs treatment. Proteomics study identified 88 high stringent differentially expressed proteins comparing the three treatment groups with controls. CONCLUSION: These findings demonstrated a promising detection specificity and treatment efficacy for our system (SiNPs-TZ, 1:8 Hc-TZ), encouraging its potential use as a new theranostic agent for HER2-positive BC lesions. In addition, proteomic profile confirmed that a set of proteins, related to tumor aggressiveness, were positively affected by targeted nanoparticles.

H-Ferritin nanoparticle-mediated delivery of antibodies across a BBB in vitro model for treatment of brain malignancies.

Brain cancers are a group of neoplasms that can be either primary, such as glioblastoma multiforme (GBM), or metastatic, such as the HER2+ breast cancer brain metastasis. The brain represents a sanctuary for cancer cells thanks to the presence of the blood brain barrier (BBB) that controls trafficking of molecules, protecting the brain from toxic substances including drugs. Considering that GBM and HER2+ breast cancer brain metastases are characterized by EGFR and HER2 over-expression respectively, CTX- and TZ-based treatment could be effective. Several studies show that these monoclonal antibodies (mAbs) exert both a cytostatic activity interfering with the transduction pathways of EGFR family and a cytotoxic activity mainly through the immune system activation via the antibody dependent cell-mediated cytotoxicity (ADCC). Since the major limitation to therapeutic mAbs application is the presence of the BBB, here we use a recombinant form of human apoferritin (HFn) as a nanovector to promote the delivery of mAbs to the brain for the activation of the ADCC response. Using a transwell model of the BBB we proved the crossing ability of HFn-mAb. Cellular uptake of HFn-mAb by human cerebral microvascular endothelial cells (hCMEC/D3) was demonstrated by confocal microscopy. Moreover, after crossing the endothelial monolayer, HFn-conjugated mAbs retain their biological activity against targets, as assessed by MTS and ADCC assays. Our data support the use of HFn as efficient carrier to enhance the BBB crossing of mAbs, without affecting their antitumoral activity.

The Vault Nanoparticle: A Gigantic Ribonucleoprotein Assembly Involved in Diverse Physiological and Pathological Phenomena and an Ideal Nanovector for Drug Delivery and Therapy.

The vault nanoparticle is a eukaryotic ribonucleoprotein complex consisting of 78 individual 97 kDa-"major vault protein" (MVP) molecules that form two symmetrical, cup-shaped, hollow halves. It has a huge size (72.5 × 41 × 41 nm) and an internal cavity, wherein the vault poly(ADP-ribose) polymerase (vPARP), telomerase-associated protein-1 (TEP1), and some small untranslated RNAs are accommodated. Plenty of literature reports on the biological role(s) of this nanocomplex, as well as its involvement in diseases, mostly oncological ones. Nevertheless, much has still to be understood as to how vault participates in normal and pathological mechanisms. In this comprehensive review, current understanding of its biological roles is discussed. By different mechanisms, vault's individual components are involved in major cellular phenomena, which result in protection against cellular stresses, such as DNA-damaging agents, irradiation, hypoxia, hyperosmotic, and oxidative conditions. These diverse cellular functions are accomplished by different mechanisms, mainly gene expression reprogramming, activation of proliferative/prosurvival signaling pathways, export from the nucleus of DNA-damaging drugs, and import of specific proteins. The cellular functions of this nanocomplex may also result in the onset of pathological conditions, mainly (but not exclusively) tumor proliferation and multidrug resistance. The current understanding of its biological roles in physiological and pathological processes should also provide new hints to extend the scope of its exploitation as a nanocarrier for drug delivery.

Modeling the interaction of amphiphilic polymer nanoparticles with biomembranes to Guide rational design of drug delivery systems.

Nanoparticle assisted drug delivery to the cytoplasm is limited by sequestration of nanoparticles in endosomes. Endosomal escape through polymer-induced membrane destabilization is one of a few well characterized mechanisms to overcome it. Aiming to utilize this method in vivo, it is necessary to understand how modulating the structural and chemical features of the polymer and the presence of proteins in biological fluids can affect this activity. Here, as a model for the endosomal membrane, we use the membrane of red blood cells to evaluate the membrane destabilization ability of a model amphiphilic polymer in the presence of blood plasma using a hemolysis assay. This allows determination of red blood cells membrane permeabilization through the quantification of hemoglobin leakage. Our results showed a strong inhibitory effect of plasma, and that hemolytic activity can be improved by chemical modification of the polymeric micelle, reducing its interaction with plasma proteins. Finally, a second mechanism of pH-induced direct diffusion is proposed and tested using an oil/water partitioning model. These results offer a body of knowledge to improve delivery of drugs across biological membranes using carefully designed polymeric nanocarriers.

Functionalization of colloidal nanoparticles with a discrete number of ligands based on a "HALO-bioclick" reaction.

A recombinant HALO-GFP fusion protein was designed and isolated to demonstrate the feasibility of controlling the number and orientation of protein ligands to be conjugated on colloidal gold nanoparticles. AuNPs functionalized with exactly one or exactly two GFP molecules exhibited fully preserved functionality of the protein. The method is very straightforward and generally provides highly bioactive nanoparticle-protein conjugates.

Engineered Ferritin Nanoparticles for the Bioluminescence Tracking of Nanodrug Delivery in Cancer.

The identification of a highly sensitive method to check the delivery of administered nanodrugs into the tumor cells is a crucial step of preclinical studies aimed to develop new nanoformulated cures, since it allows the real therapeutic potential of these devices to be forecast. In the present work, the ability of an H-ferritin (HFn) nanocage, already investigated as a powerful tool for cancer therapy thanks to its ability to actively interact with the transferrin receptor 1, to act as an efficient probe for the monitoring of nanodrug delivery to tumors is demonstrated. The final formulation is a bioluminescent nanoparticle, where the luciferin probe is conjugated on nanoparticle surface by means of a disulfide containing linker (Luc-linker@HFn) which is subjected to glutathione-induced cyclization in tumor cell cytoplasm. The prolonged imaging of luciferase+ tumor models, demonstrated by an in vitro and an in vivo approach, associated with the prolonged release of luciferin into cancer cells by disulfide bridge reduction, clearly indicates the high efficiency of Luc-linker@HFn for drug delivery to the tumor tissues.

Colloidal polymer-coated Zn-doped iron oxide nanoparticles with high relaxivity and specific absorption rate for efficient magnetic resonance imaging and magnetic hyperthermia.

Colloidally stable nanoparticles-based magnetic agents endowed with very high relaxivity and specific absorption rate are extremely desirable for efficient magnetic resonance imaging and magnetic hyperthermia, respectively. Here, we report a water dispersible magnetic agent consisting of zinc-doped superparamagnetic iron oxide nanoparticles (i.e., Zn-SPIONs) of 15 nm size with high saturation magnetization coated with an amphiphilic polymer for effective magnetic resonance imaging and magnetic hyperthermia of glioblastoma cells. These biocompatible polymer-coated Zn-SPIONs had 24 nm hydrodynamic diameter and exhibited high colloidal stability in various aqueous media, very high transverse relaxivity of 471 mM-1 s-1, and specific absorption rate up to 743.8 W g-1, which perform better than most iron oxide nanoparticles reported in the literature, including commercially available agents. Therefore, using these polymer-coated Zn-SPIONs even at low concentrations, T2-weighted magnetic resonance imaging and moderate magnetic hyperthermia of glioblastoma cells under clinically relevant magnetic field were successfully implemented. In addition, the results of this in vitro study suggest the superior potential of Zn-SPIONs as a theranostic nanosystem for brain cancer treatment, simultaneously acting as a contrast agent for magnetic resonance imaging and a heat mediator for localized magnetic hyperthermia.

Monitoring the Fate of Orally Administered PLGA Nanoformulation for Local Delivery of Therapeutic Drugs.

One of the goals of the pharmaceutical sciences is the amelioration of targeted drug delivery. In this context, nanocarrier-dependent transportation represents an ideal method for confronting a broad range of human disorders. In this study, we investigated the possibility of improving the selective release of the anti-cancer drug paclitaxel (PTX) in the gastro-intestinal tract by encapsulating it into the biodegradable nanoparticles made by FDA-approved poly(lactic-co-glycolic acid) (PLGA) and coated with polyethylene glycol to improve their stability (PLGA-PEG-NPs). Our study was performed by combining the synthesis and characterization of the nanodrug with in vivo studies of pharmacokinetics after oral administration in mice. Moreover, fluorescent PLGA-nanoparticles (NPs), were tested both in vitro and in vivo to observe their fate and biodistribution. Our study demonstrated that PLGA-NPs: (1) are stable in the gastric tract; (2) can easily penetrate inside carcinoma colon 2 (CaCo2) cells; (3) reduce the PTX absorption from the gastrointestinal tract, further limiting systemic exposure; (4) enable PTX local targeting. At present, the oral administration of biodegradable nanocarriers is limited because of stomach degradation and the sink effect played by the duodenum. Our findings, however, exhibit promising evidence towards our overcoming these limitations for a more specific and safer strategy against gastrointestinal disorders.