Novel Nanoparticles Based on N,O-Carboxymethyl Chitosan-Dopamine Amide Conjugate for Nose-to-Brain Delivery

A widely investigated approach to bypass the blood brain barrier is represented by the intranasal delivery of therapeutic agents exploiting the olfactory or trigeminal connections nose-brain. As for Parkinson’s disease (PD), characterized by dopaminergic midbrain neurons degeneration, currently there is no disease modifying therapy. Although several bio-nanomaterials have been evaluated for encapsulation of neurotransmitter dopamine (DA) or dopaminergic drugs in order to restore the DA content in parkinsonian patients, the premature leakage of the therapeutic agent limits this approach. To tackle this drawback, we undertook a study where the active was linked to the polymeric backbone by a covalent bond. Thus, novel nanoparticles (NPs) based on N,O-Carboxymethylchitosan-DA amide conjugate (N,O-CMCS-DA) were prepared by the nanoprecipitation method and characterized from a technological view point, cytotoxicity and uptake by Olfactory Ensheating Cells (OECs). Thermogravimetric analysis showed high chemical stability of N,O-CMCS-DA NPs and X-ray photoelectron spectroscopy evidenced the presence of amide linkages on the NPs surface. MTT test indicated their cytocompatibility with OECs, while cytofluorimetry and fluorescent microscopy revealed the internalization of labelled N,O-CMCS-DA NPs by OECs, that was increased by the presence of mucin. Altogether, these findings seem promising for further development of N,O-CMCS-DA NPs for nose-to-brain delivery application in PD.

Overcoming MDR by Associating Doxorubicin and pH-Sensitive PLGA Nanoparticles Containing a Novel Organoselenium Compound—An In Vitro Study

In this study, we developed PLGA nanoparticles (NPs) as an effective carrier for 5′-Se-(phenyl)-3-(amino)-thymidine (ACAT-Se), an organoselenium compound, nucleoside analogue that showed promising antitumor activity in vitro. The PLGA NPs were prepared by the nanoprecipitation method and modified with a pH-responsive lysine-based surfactant (77KL). The ACAT-Se-PLGA-77KL-NPs presented nanometric size (around 120 nm), polydispersity index values <0.20 and negative zeta potential values. The nanoencapsulation of ACAT-Se increased its antioxidant (DPPH and ABTS assays) and antitumor activity in MCF-7 tumor cells. Hemolysis study indicated that ACAT-Se-PLGA-77KL-NPs are hemocompatible and that 77KL provided a pH-sensitive membranolytic behavior to the NPs. The NPs did not induce cytotoxic effects on the nontumor cell line 3T3, suggesting its selectivity for the tumor cells. Moreover, the in vitro antiproliferative activity of NPs was evaluated in association with the antitumor drug doxorubicin. This combination result in synergistic effect in sensitive (MCF-7) and resistant (NCI/ADR-RES) tumor cells, being especially able to successfully sensitize the MDR cells. The obtained results suggested that the proposed ACAT-Se-loaded NPs are a promising delivery system for cancer therapy, especially associated with doxorubicin.

Oromucosal Alginate Films with Zein Nanoparticles as a Novel Delivery System for Digoxin

Digoxin is a hydrophobic drug used for the treatment of heart failure that possesses a narrow therapeutic index, which raises safety concerns for toxicity. This is of utmost relevance in specific populations, such as the elderly. This study aimed to demonstrate the potential of the sodium alginate films as buccal drug delivery system containing zein nanoparticles incorporated with digoxin to reduce the number of doses, facilitating the administration with a quick onset of action. The film was prepared using the solvent casting method, whereas nanoparticles by the nanoprecipitation method. The nanoparticles incorporated with digoxin (0.25 mg/mL) exhibited a mean size of 87.20 ± 0.88 nm, a polydispersity index of 0.23 ± 0.00, and a zeta potential of 21.23 ± 0.07 mV. Digoxin was successfully encapsulated into zein nanoparticles with an encapsulation efficiency of 91% (±0.00). Films with/without glycerol and with different concentrations of ethanol were produced. The sodium alginate (SA) films with 10% ethanol demonstrated good performance for swelling (maximum of 1474%) and mechanical properties, with a mean tensile strength of 0.40 ± 0.04 MPa and an elongation at break of 27.85% (±0.58), compatible with drug delivery application into the buccal mucosa. The current study suggests that SA films with digoxin-loaded zein nanoparticles can be an effective alternative to the dosage forms available on the market for digoxin administration.

Irinotecan Loaded Lipomers: Development, And Characterization For Proof of Concept To Combat Colon Cancer

PLGA Poly (lactide-co-Glycolide) is a biocompatible and biodegradable copolymer gained popularity for tissue engineering, drug delivery, biosensing, and biomedical applications. In the present study PLGA of (Mw =13,900) has synthesized by ring opening polymerization with zinc proline initiator. Irinotecan (Ir) loaded Lipomers (LPs) formulated with PLGA, DSPE-PEG (2000) (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino (polyethylene glycol)-2000) and soya lecithin excipients by nanoprecipitation method. These formulated LPs further validated by physicochemical and biological potential for colon delivery applications. The potential of LPs for delivery of Irinotecan (Ir), a poorly water-soluble chemotherapeutic drug used for the treatment of colon cancer was studied. LPs of controlled size (80-120 nm), surface charge (~ -35 mV), sustained release potential and significant cytotoxicity against CT-26 (colon) cancer cells, were successfully prepared. In-vivo biodistribution and tumor site retention in CT-26 xenografts tumor bearing Balb/C mice showed promising result for tumor uptake and retention for prolong time period. Unlike P-DSPE-Ir, PEG coated P-DSPE-PEG-Ir LPs exhibit significant tumor growth delay compared to untreated and blank formulation treated groups in the CT-26 subcutaneous tumor model, after 4 treatments of 10 mg Ir/kg dose. The biocompatibility, safety of LPs confirmed by acute toxicity study of optimized formulation. Overall, this proof-of-concept study demonstrates that the LPs improved efficacy, bioavailability and decreases neutropenia of Ir to combat colon cancer.

Studies on the Preparation of Nanoparticles from Betulin-Based Polyanhydrides

Nanoparticles were obtained by nanoprecipitation and by emulsion solvent evaporation (ESE) method. In the ESE method, the size of the particles depended on the type and concentration of surfactant (in the water phase) and the polymer concentration (in the organic phase). The best results were obtained with ionic surfactants, however, the use of such compounds may accelerate the degradation process of polymers. In the nanoprecipitation method, the ratio of solvent (methylene chloride) to non-solvent (hexane) has a significant influence on the particle size. The smallest particles were obtained with a solvent to non-solvent ratio of 1:150.

Effect of Cisplatin/Curcumin-Loaded Polycaprolactone Nanoparticles on Oral Carcinoma Cells

This work aimed to investigate the effect of cisplatin (CDDP)/curcumin (Cur)-loaded polycaprolactone nanoparticles (PCL-NPs) on an oral epidermal carcinoma cell line. PCL-NPs were fabricated using nanoprecipitation method employing poly(vinyl alcohol) and polysorbate 80 as stabilizers. Two anticancer compounds, CDDP and Cur, were incorporated into the PCL-NPs by entrapment technique. The physical characteristics of the NPs were evaluated. The presence of the drugs on the NPs was ascertained using Attenuated total reflection Fourier-transformed infrared (ATR-FTIR) spectroscopy, and the drug content was quantified by indirect method using ultraviolet spectroscopy and inductive coupled plasma-mass spectroscopy. The cytotoxic effect was demonstrated using MTT assay and the synergistic effect of both drugs was calculated by the combination index method using CompuSyn® software. The findings revealed that the PCL-NPs were less than 300 nm with narrow size distribution. The appropriate drug concentration for drug loading was 0.12 mg/mL of Cur and 0.02 mg/mL of CDDP, providing approximately 70% and 80% loading efficacy, respectively. The improved anticancer effect was observed in the cells treated with mixture of the drugs and the NPs loaded with dual drugs. Above all, CDDP/Cur-loaded PCL-NPs were successfully prepared. The delivery system exhibited good anticancer effect against oral cancer cells which may be attributed to the synergism effect of CDDP and Cur loaded on the NPs.

Microfluidic Technology for the Production of Hybrid Nanomedicines

Microfluidic technologies have recently been applied as innovative methods for the production of a variety of nanomedicines (NMeds), demonstrating their potential on a global scale. The capacity to precisely control variables, such as the flow rate ratio, temperature, total flow rate, etc., allows for greater tunability of the NMed systems that are more standardized and automated than the ones obtained by well-known benchtop protocols. However, it is a crucial aspect to be able to obtain NMeds with the same characteristics of the previously optimized ones. In this study, we focused on the transfer of a production protocol for hybrid NMeds (H-NMeds) consisting of PLGA, Cholesterol, and Pluronic® F68 from a benchtop nanoprecipitation method to a microfluidic device. For this aim, we modified parameters such as the flow rate ratio, the concentration of core materials in the organic phase, and the ratio between PLGA and Cholesterol in the feeding organic phase. Outputs analysed were the chemico–physical properties, such as size, PDI, and surface charge, the composition in terms of %Cholesterol and residual %Pluronic® F68, their stability to lyophilization, and the morphology via atomic force and electron microscopy. On the basis of the results, even if microfluidic technology is one of the unique procedures to obtain industrial production of NMeds, we demonstrated that the translation from a benchtop method to a microfluidic one is not a simple transfer of already established parameters, with several variables to be taken into account and to be optimized.

High Solubilization and Controlled Release of Paclitaxel Using Thermosponge Nanoparticles for Effective Cancer Therapy

Cancer, which is a leading cause of death, contributes significantly to reducing life expectancy worldwide. Even though paclitaxel (PTX) is known as one of the main anticancer drugs, it has several limitations, including low solubility in aqueous solutions, a limited dosage range, an insufficient release amount, and patient resistance. To overcome these limitations, we suggest the development of PTX-loaded thermosponge nanoparticles (PTX@TNP), which result in improved anticancer effects, via a simple nanoprecipitation method, which allows the preparation of PTX@TNPs with hydrophobic interactions without any chemical conjugation. Further, to improve the drug content and yield of the prepared complex, the co-organic solvent ratio was optimized. Thus, it was observed that the drug release rate increased as the drug capacity of PTX@TNPs increased. Furthermore, increasing PTX loading led to considerable anticancer activity against multidrug resistance (MDR)-related colorectal cancer cells (HCT 15), implying a synergistic anticancer effect. These results suggest that the solubilization of high drug amounts and the controlled release of poorly water-soluble PTX using TNPs could significantly improve its anticancer therapy, particularly in the treatment of MDR-p-glycoprotein-overexpressing cancers.

mPEG-PCL Nanoparticles as New Carriers for Delivery of a Prostae Cancer Drug Fluamide

The present work was aimed to prepare and evaluate Flutamide loaded methoxy poly (ethylene glycol) poly caprolactone (mPEG–PCL) nanoparticles for targeted delivery to the prostate cancer. The nanoparticles (NPs) were prepared by 23 factorial design and nanoprecipitation method. Various trials were evaluated for surface morphology, particle size and zeta potential. The influences of three formulation excipients such as polymer, stabilizer and organic phase volume on the characterization of NPs were investigated. The results of fourier transform infrared (FTIR) studies were indicated no interaction between the drug and polymer. The particle size varied from 79.2 to 89.1 nm and zeta potential value was found to be - 41.5 mv. The surface morphology of NPs was observed using scanning electron microscopy (SEM) and understands the arrangement and orientation of NPs to determine its behavior and stability. Flutamide loaded mPEG–PCL nanoparticle is a potential new carrier system for treatment of prostate cancer, which may overcome the problems associated with conventional formulations such as tablets.