Design and in vitro assessment of chitosan nanocapsules for the pulmonary delivery of rifabutin.

Tuberculosis (TB) is a life-threatening disease and a main cause of death worldwide. It mainly affects the lungs, and it is attributed to the infection with Mycobacterium tuberculosis (MTB). Current treatments consist of the oral administration of combinations of antibiotics including rifabutin, in high doses and for long periods of time.

Microencapsulated Isoniazid-Loaded Metal-Organic Frameworks for Pulmonary Administration of Antituberculosis Drugs.

Tuberculosis (TB) is an infectious disease that causes a great number of deaths in the world (1.5 million people per year). This disease is currently treated by administering high doses of various oral anti-TB drugs for prolonged periods (up to 2 years).

Microencapsulated Chitosan-Based Nanocapsules: A New Platform for Pulmonary Gene Delivery.

In this work, we propose chitosan (CS)-based nanocapsules (NCs) for pulmonary gene delivery. Hyaluronic acid (HA) was incorporated in the NCs composition (HA/CS NCs) aiming to promote gene transfection in the lung epithelium. NCs were loaded with a model plasmid (pCMV-βGal) to easily evaluate their transfection capacity.

A Traffic Light System to Maximize Carbohydrate Cryoprotectants' Effectivity in Nanostructured Lipid Carriers' Lyophilization.

Lyophilization is often employed to transform nanoparticle suspensions to stable solid forms. This work proposed Neurofuzzy Logic (NFL) to better understand the lyophilization process of Nanostructured Lipid Carriers' (NLCs) dispersions and the carbohydrate cryoprotectants' (CPs) performance in these processes. NLCs were produced by hot homogenization, frozen at different speeds, and lyophilized using several CPs at variable concentrations.

Rifabutin-Loaded Nanostructured Lipid Carriers as a Tool in Oral Anti-Mycobacterial Treatment of Crohn's Disease.

Oral anti-mycobacterial treatment of Crohn's disease (CD) is limited by the low aqueous solubility of drugs, along with the altered gut conditions of patients, making uncommon their clinical use. Hence, the aim of the present work is focused on the in vitro evaluation of rifabutin (RFB)-loaded Nanostructured lipid carriers (NLC), in order to solve limitations associated to this therapeutic approach. RFB-loaded NLC were prepared by hot homogenization and characterized in terms of size, polydispersity, surface charge, morphology, thermal stability, and drug payload and release.

Covalently and ionically, dually crosslinked chitosan nanoparticles block quorum sensing and affect bacterial cell growth on a cell-density dependent manner.

In our efforts to improve the quality and stability of chitosan nanoparticles (NPs), we describe here a new type of chitosan NPs dually crosslinked with genipin and sodium tripolyphosphate (TPP) that display quorum quenching activity. These NPs were created using a simplified and robust procedure that resulted in improved physicochemical properties and enhanced stability. This procedure involves the covalent crosslinking of chitosan with genipin, followed by the formation of chitosan NPs by ionic gelation with TPP.

Metal-Organic Framework Microsphere Formulation for Pulmonary Administration.

Although nanoscaled metal-organic frameworks (nanoMOFs) are promising drug carriers, their appropriate formulation remains almost unexplored and basically restricted to intravenous routes. Lungs, beneficiating from a large absorption surface and low enzymatic presence, are a very attractive target for both local and systemic delivery. However, pulmonary nanoMOF formulation is a pending and defying task.

Effect of the ultrastructure of chitosan nanoparticles in colloidal stability, quorum quenching and antibacterial activities.

We have fabricated two types of crosslinked chitosan-based nanoparticles (NPs), namely (1) ionically crosslinked with tripolyphosphate (TPP), designated as IC-NPs and (2) dually co-crosslinked (ionically and covalently with TPP and genipin, respectively) termed CC-NPs. The two types of NPs were physichochemically characterized by means of DLS-NIBS, synchrotron SAXS and M3-PALS (zeta potential). First, we found that covalent co-crosslinking of ionically pre-crosslinked nanoparticles yielded monodisperse CC-NPs in the size range of ∼200 nm, whereas the parental IC-NPs remained highly polydisperse.

Transfection of pulmonary cells by stable pDNA-polycationic hybrid nanostructured particles.

Aim: Cationically modified solid lipid nanoparticles (SLN) were investigated as plasmid DNA (pDNA) carriers and transfection agents for the pulmonary route.

Materials & Methods: pDNA-loaded SLN were produced using glyceryl dibehenate or tristearate as matrix lipids and chitosan as surface charge modifier, and encapsulated by spray-drying in mannitol and trehalose microspheres.

Results: Nanoparticles of 200 nm, and zeta potential around +15 mV were produced.

Delimiting the knowledge space and the design space of nanostructured lipid carriers through Artificial Intelligence tools.

Nanostructured lipid carriers (NLC) are biocompatible and biodegradable nanoscale systems with extensive application for controlled drug release. However, the development of optimal nanosystems along with a reproducible manufacturing process is still challenging. In this study, a two-step experimental design was performed and databases were successfully modelled using Artificial Intelligence techniques as an innovative method to get optimal, reproducible and stable NLC.

Micro/nanostructured inhalable formulation based on polysaccharides: Effect of a thermoprotectant on powder properties and protein integrity.

Combined micro- and nanosystems are appealing for pulmonary protein delivery, fulfilling the specific physiological requirements for efficient outcomes in-vivo. However, fabrication of protein formulations may impose stresses perturbing protein conformational stability and, hence, biological activity. Herein, a protein, insulin (INS), was nanoencapsulated inside chitosan nanoparticles (CS NPs) by ionic gelation.

Microencapsulated Solid Lipid Nanoparticles as a Hybrid Platform for Pulmonary Antibiotic Delivery.

Solid lipid nanoparticles (SLN) containing rifabutin (RFB), with pulmonary administration purposes, were developed through a technique that avoids the use of organic solvents or sonication. To facilitate their pulmonary delivery, the RFB-loaded SLN were included in microspheres of appropriate size using suitable excipients (mannitol and trehalose) through a spray-drying technique. Confocal analysis microscopy showed that microspheres are spherical and that SLN are efficiently microencapsulated and homogeneously distributed throughout the microsphere matrices.

Freeze-dried cylinders carrying chitosan nanoparticles for vaginal peptide delivery.

Recently nanoparticle-based vaginal drug delivery formulations have been acquiring great attention for the administration of peptide based-vaccines or microbicides to prevent or treat sexually transmitted diseases. In this work, a straightforward and efficient strategy for the vaginal application and release of peptide-loaded mucoadhesive nanoparticles was developed. This essentially consists of chitosan nanoparticles encapsulated in suitable hydrophilic freeze-dried cylinders.

Microencapsulated SLN: An innovative strategy for pulmonary protein delivery.

Associating protein with nanoparticles is an interesting strategy to improve their bioavailability and biological activity. Solid lipid nanoparticles (SLN) have been sought as carriers for therapeutic proteins transport to the lung epithelium. Nevertheless, because of their low inertia, nanoparticles intended for pulmonary application usually escape from lung deposition.

Physical Properties and Stability of Soft Gelled Chitosan-Based Nanoparticles.

We addressed the role of the degree of acetylation (DA) and of M of chitosan (CS) on the physical characteristics and stability of soft nanoparticles obtained through either ionic cross-linking with sodium tripolyphosphate (TPP), or reverse emulsion/gelation. Each of these methods affords nanoparticles (NPs) or nanogels (NGs), respectively. The size of CS-TPP NPs comprising CS of high M (≈123-266 kDa) increases with DA (≈1.

The role of hyaluronic acid inclusion on the energetics of encapsulation and release of a protein molecule from chitosan-based nanoparticles.

The synergistic effects of the polysaccharides chitosan (CS) and hyaluronic acid (HA) formulated into hybrid nanoparticles are promising for drug delivery. In the present work, we performed a detailed analysis of the molecular interactions involved in the TPP-assisted ionotropic gelation of CS hybrid nanoparticles with the objective of investigating the impact of HA inclusion on the particle formulation and on the in vitro release of insulin (INS) as a protein cargo. To do that, an in-depth thermodynamic study was carried out by isothermal titration calorimetry (ITC), nuclear magnetic resonance (NMR) and differential scanning calorimetry (DSC) techniques.

Rifabutin-loaded solid lipid nanoparticles for inhaled antitubercular therapy: Physicochemical and in vitro studies.

Systemic administration of antitubercular drugs can be complicated by off-target toxicity to cells and tissues that are not infected by Mycobacterium tuberculosis . Delivery of antitubercular drugs via nanoparticles directly to the infected cells has the potential to maximize efficacy and minimize toxicity. The present work demonstrates the potential of solid lipid nanoparticles (SLN) as a delivery platform for rifabutin (RFB).

Hybrid nanosystems based on natural polymers as protein carriers for respiratory delivery: Stability and toxicological evaluation.

Chitosan/carrageenan/tripolyphosphate nanoparticles were previously presented as holding potential for an application in transmucosal delivery of macromolecules, with tripolyphosphate demonstrating to contribute for both size reduction and stabilisation of the nanoparticles. This work was aimed at evaluating the capacity of the nanoparticles as protein carriers for pulmonary and nasal transmucosal delivery, further assessing their biocompatibility pattern regarding that application. Nanoparticles demonstrated stability in presence of lysozyme, while freeze-drying was shown to preserve their characteristics when glucose or sucrose were used as cryoprotectants.

Development of PLGA-mannosamine nanoparticles as oral protein carriers.

Here we report the development of polymeric nanoparticles, made of poly(lactide-co-glycolide) (PLGA) chemically modified with mannosamine (MN), intended to specifically interact with the intestinal mucosa and facilitate the intestinal transport of proteins. PLGA-MN nanoparticles displayed nanometric size and a negative zeta potential, which was lower than that of the PLGA nanoparticles. This correlate well with the preferential location of the MN group on the nanoparticles surface obtained by X-ray photoelectron spectroscope (XPS).

Pullulan-based nanoparticles as carriers for transmucosal protein delivery.

Polymeric nanoparticles have revealed very effective in transmucosal delivery of proteins. Polysaccharides are among the most used materials for the production of these carriers, owing to their structural flexibility and propensity to evidence biocompatibility and biodegradability. In parallel, there is a preference for the use of mild methods for their production, in order to prevent protein degradation, ensure lower costs and easier procedures that enable scaling up.

Chitosan-hyaluronic acid nanoparticles for gene silencing: the role of hyaluronic acid on the nanoparticles' formation and activity.

Hyaluronic acid (HA) has been described as a biocompatibility enhancer for gene delivery systems; however, the mechanistic implications of its inclusion on the formation and activity of such systems and subsequent gene release are poorly understood. To better understand these issues, we describe herein the preparation and characterization of chitosan and chitosan-hyaluronic acid nanoparticles (CS and CS:HA NPs) for gene silencing. Different formulations were prepared by ionotropic gelation and evaluated for their physicochemical properties and biological activities in A549-Luc cells.

Microencapsulated chitosan nanoparticles for pulmonary protein delivery: in vivo evaluation of insulin-loaded formulations.

This work presents a new dry powder system consisting of microencapsulated protein-loaded chitosan nanoparticles (CS NPs). The developed system was evaluated in vivo in rats in order to investigate its potential to transport insulin (INS), a model protein, to the deep lung, where it is absorbed into systemic circulation. The INS-loaded CS NPs were prepared by ionotropic gelation and characterized for morphology, size, zeta potential, association efficiency and loading capacity.

Mucosal delivery of liposome-chitosan nanoparticle complexes.

Designing adequate drug carriers has long been a major challenge for those working in drug delivery. Since drug delivery strategies have evolved for mucosal delivery as the outstanding alternative to parenteral administration, many new drug delivery systems have been developed which evidence promising properties to address specific issues. Colloidal carriers, such as nanoparticles and liposomes, have been referred to as the most valuable approaches, but still have some limitations that can become more inconvenient as a function of the specific characteristics of administration routes.

Chitosan-alginate blended nanoparticles as carriers for the transmucosal delivery of macromolecules.

Nanoparticles intended for use in the transmucosal delivery of macromolecules were prepared by the ionic gelation of chitosan (CS) hydrochloride with pentasodium tripolyphosphate (TPP) and concomitant complexation with sodium alginate (ALG). The incorporation of a small proportion of ALG of increasing molecular weight (M(w); from 4 to 74 kDa) into the nanoparticles led to a monotonic increase in colloidal size from ∼260 to ∼525 nm. This increase in size was regarded as a consequence of the formation of gradually more expanded structures.

New generation of hybrid poly/oligosaccharide nanoparticles as carriers for the nasal delivery of macromolecules.

We have recently reported a new generation of polysaccharide nanoparticles consisting of chitosan (CS) and cyclodextrin (CD) derivatives, which exhibit a number of advantages when compared to the classical CS nanoparticles. In the present work our goal was to explore the potential of these hybrid CS/CD nanoparticles as carriers for the nasal delivery of macromolecules. First, we evaluated the effect of the amount and type of CD (sulfobutylether-beta-CD or carboximethyl-beta-CD) on the physicochemical properties of the nanocarriers.