Inkjet printing of a thermolabile model drug onto FDM-printed substrates: formulation and evaluation.

Objective: The inkjet printing (IP) and fused deposition modeling (FDM) technologies have emerged in the pharmaceutical field as novel and personalized formulation approaches. Specific manufacturing factors must be considered in each adopted methodology, i.e.

Polymer-Lipid Microparticles for Pulmonary Delivery.

Toward engineering approaches that are designed to optimize the particle size, morphology, and mucoadhesion behavior of the particulate component of inhaler formulations, this paper presents the preparation, physicochemical characterization, and preliminary in vitro evaluation of multicomponent polymer-lipid systems that are based on "spray-drying engineered" α-lactose monohydrate microparticles. The formulations combine an active (budesonide) with a lung surfactant (dipalmitoylphosphatidylcholine) and with materials that are known for their desirable effects on morphology (polyvinyl alcohol), aerosolization (l-leucine), and mucoadhesion (chitosan). The effect of the composition of formulations on the morphology, distribution, and in vitro mucoadhesion profiles is presented along with "Calu-3 cell monolayers" data that indicate good cytocompatibility and also with simulated-lung-fluid data that are consistent with the therapeutically useful release of budesonide.

Towards carborane-functionalised structures for the treatment of brain cancer.

Boron neutron capture therapy (BNCT) is a promising targeted chemoradiotherapeutic technique for the management of invasive brain tumors, such as glioblastoma multiforme (GBM). A prerequisite for effective BNCT is the selective targeting of tumour cells with B-rich therapeutic moieties. To this end, polyhedral boranes, especially carboranes, have received considerable attention because they combine a high boron content with relative low toxicity and metabolic inertness.

Correction: Boron-containing delocalised lipophilic cations for the selective targeting of cancer cells.

[This corrects the article DOI: 10.1039/C6MD00383D.].

Nano carriers for drug transport across the blood-brain barrier.

Effective therapy lies in achieving a therapeutic amount of drug to the proper site in the body and then maintaining the desired drug concentration for a sufficient time interval to be clinically effective for treatment. The blood-brain barrier (BBB) hinders most drugs from entering the central nervous system (CNS) from the blood stream, leading to the difficulty of delivering drugs to the brain via the circulatory system for the treatment, diagnosis and prevention of brain diseases. Several brain drug delivery approaches have been developed, such as intracerebral and intracerebroventricular administration, intranasal delivery and blood-to-brain delivery, as a result of transient BBB disruption induced by biological, chemical or physical stimuli such as zonula occludens toxin, mannitol, magnetic heating and ultrasound, but these approaches showed disadvantages of being dangerous, high cost and unsuitability for most brain diseases and drugs.

Pharmacological Development of Target-Specific Delocalized Lipophilic Cation-Functionalized Carboranes for Cancer Therapy.

Purpose: Tumor cell heterogeneity and microenvironment represent major hindering factors in the clinical setting toward achieving the desired selectivity and specificity to malignant tissues for molecularly targeted cancer therapeutics. In this study, the cellular and molecular evaluation of several delocalized lipophilic cation (DLC)-functionalized carborane compounds as innovative anticancer agents is presented.

Methods: The anticancer potential assessment of the DLC-carboranes was performed in established normal (MRC-5, Vero), cancer (U-87 MG, HSC-3) and primary glioblastoma cancer stem (EGFR(pos), EGFR(neg)) cultures.

An evaluation of the adhesion of solid oral dosage form coatings to the oesophagus.

There is a requirement for the development of oral dosage forms that are adhesive and allow extended oesophageal residence time for localised therapies, or are non-adhesive for ease of swallowing. This study provides an initial assessment of the in vitro oesophageal retention characteristics of several widely utilised pharmaceutical coating materials. To this end, a previously described apparatus has been used to measure the force required to pull a coated disc-shaped model tablet across a section of excised oesophageal tissue.

Nanoparticles of alkylglyceryl-dextran-graft-poly(lactic acid) for drug delivery to the brain: Preparation and in vitro investigation.

Poly(lactic acid), which has an inherent tendency to form colloidal systems of low polydispersity, and alkylglyceryl-modified dextran - a material designed to combine the non-immunogenic and stabilising properties of dextran with the demonstrated permeation enhancing ability of alkylglycerols - have been combined for the development of nanoparticulate, blood-brain barrier-permeating, non-viral vectors. To this end, dextran, that had been functionalised via treatment with epoxide precursors of alkylglycerol, was covalently linked to poly(lactic acid) using a carbodiimide cross-linker to form alkylglyceryl-modified dextran-graft-poly(lactic acid). Solvent displacement and electrospray methods allowed the formulation of these materials into nanoparticles having a unimodal size distribution profile of about 100-200nm and good stability at physiologically relevant pH (7.

Multifunctional star-shaped polylactic acid implants for use in angioplasty.

Towards the development of new biomaterials for use in angioplasty, star-shaped polylactic acids have been synthesised and shown to adhere well to living cells, by in vitro and in vivo experiments, and to hydrolyse over time in a physiologically relevant environment into biocompatible and bioabsorbable entities that are capable of bestowing properties of anticoagulation and angiogenesis to their living host.

Towards boron neutron capture therapy: the formulation and preliminary in vitro evaluation of liposomal vehicles for the therapeutic delivery of the dequalinium salt of bis-nido-carborane.

Liposomes of phosphatidylcholine or of dimyristoylphosphatidylcholine that incorporate bis-nido-carborane dequalinium salt are stable in physiologically relevant media and have in vitro toxicity profiles that appear to be compatible with potential therapeutic applications. These features render the structures suitable candidate boron-delivery vehicles for evaluation in the boron neutron capture therapy of cancer.

Toward mucoadhesive hydrogel formulations for the management of xerostomia: the physicochemical, biological, and pharmacological considerations.

Although hydrogel formulations that may be applied to many mucosal surfaces are now readily accessible, little research effort has been concentrated on the development of systems that may be usefully employed for the prolonged hydration of the oral cavity. To this end, and set within the context of oral care in general, this review considers the requirements for the design of hydrogel formulations with an affinity for buccal cells and details methods for evaluating the performance of these formulations as treatments for the management of xerostomia.

An in vitro model for the evaluation of the adhesion of solid oral dosage forms to the oesophagus.

Adhesion of solid oral dosage forms to the oesophagus can be a disadvantage when delivering drugs that may cause oesophageal damage, or can be an advantage when developing localised therapies for this region. In this study, apparatus to investigate coatings that may influence oesophageal retention was developed and evaluated. The apparatus incorporated a section of porcine oesophageal mucosa held flat by the application of a gentle vacuum and kept moist by the application of a simulated saliva solution.

A once-a-day dosage form for the delivery of insulin through the nasal route: in vitro assessment and in vivo evaluation.

An in situ thermogelling, mucoadhesive formulation based on N-trimethyl chitosan chloride has been evaluated for its potential to affect the transmucosal delivery of insulin via the nasal route. In vitro studies at a physiologically relevant temperature (ca. 35 °C) have shown that the formulation releases most of its insulin load (ca.

Hydrogels in mucosal delivery.

The concept of mucoadhesion and the molecular design requirements for the synthesis of mucoadhesive agents are both well understood and, as a result, hydrogel formulations that may be applied to mucosal surfaces are readily accessible. Nanosized hydrogel systems that make use of biological recognition or targeting motifs, by reacting to disease-specific environmental triggers and/or chemical signals to affect drug release, are now emerging as components of a new generation of therapeutics that promise improved residence time, faster response to stimuli and triggered release.

Intestine-Specific, Oral Delivery of Captopril/Montmorillonite: Formulation and Release Kinetics.

The intercalation of captopril (CP) into the interlayers of montmorillonite (MMT) affords an intestine-selective drug delivery system that has a captopril-loading capacity of up to ca. 14 %w/w and which exhibits near-zero-order release kinetics.

In vitro effect on cancer cells: synthesis and preparation of polyurethane membranes for controlled delivery of curcumin.

Urethane polymers (PU) have been prepared from low-molecular weight polylactic acid (PLA) and hexamethylene diisocyanate (HMDI) using polydimethylsiloxane (PDMS) as a chain extender. These formed the supporting polymeric matrix of curcumin-containing PU membranes which were prepared using a solvent evaporation technique. FTIR and XRD data indicated the molecular-level dispersion and random distribution of curcumin in the polymer matrix, and data were consistent with observations from tensile-strength measurements and from AFM imaging.

The formulation of polyhedral boranes for the boron neutron capture therapy of cancer.

The early promise of boron neutron capture therapy as a method for the treatment of cancer has been inhibited by the inherent toxicity associated with therapeutically useful doses of ¹⁰B-containing pharmacophores, the need for target-tissue specificity and the challenges imposed by biological barriers. Although developments in the synthetic chemistry of polyhedral boranes have addressed issues of toxicity to a considerable extent, the optimisation of the transport and the delivery of boronated agents to the site of action--the subject of this review--is a challenge that is addressed by the development of innovative formulation strategies.

Multifunctional poly(alkyl methacrylate) films for dental care.

Towards the evaluation of non-permanent dental coatings for their capacity to impart dental-care benefits, thin films of a homologous series of comb-like poly(alkyl methacrylate)s (ethyl to octadecyl) have been deposited, from aqueous latex formulations, onto dentally relevant substrates. AFM studies have shown that the thickness (40-300 nm) and surface roughness (8-12 nm) of coherent polymer films are influenced by the degree of polymerization and by the length of the pendant chain. Of the polymers under consideration, poly(butyl methacrylate) formed a close-packed film that conferred to dental substrates a high degree of inhibition to acid-mediated erosion (about 27%), as evaluated by released-phosphate determinations.

Thermosensitive hydrogels for nasal drug delivery: the formulation and characterisation of systems based on N-trimethyl chitosan chloride.

Towards the development of a thermosensitive drug-delivery vehicle for nasal delivery, a systematic series of N-trimethyl chitosan chloride polymers, synthesised from chitosans of three different average molecular weights, have been co-formulated into a hydrogel with poly(ethylene glycol) and glycerophosphate. Rheological evaluations have shown that hydrogels derived from N-trimethyl chitosan with a low degree of quaternisation and high or medium average molecular weight exhibit relatively short sol-gel transition times at physiologically relevant temperatures. Also, the same hydrogels display good water-holding capacity and strong mucoadhesive potential, and their mixtures with mucus exhibit rheological synergy.

Toward drug delivery into the brain: synthesis, characterization, and preliminary in vitro assessment of alkylglyceryl-functionalized chitosan nanoparticles.

A series of O-substituted alkylglyceryl chitosans with systematically varied degrees of grafting was prepared through synthetic steps that involved the protection of amino moieties via phthaloylation and employed for the formulation of aqueous nanoparticulate systems that may be capable of delivering drugs to the brain. Dynamic light scattering studies have shown that nanoparticles with physiologically relevant aqueous stabilities may be prepared following the partial quaternization of these alkylglyceryl-modified chitosans. Preliminary in vitro tests using a mouse-brain endothelial cell model have indicated the efficient cellular uptake of these nanoparticles and identified butylglyceryl chitosan and butylglyceryl N,N,N-trimethyl chitosan as promising materials for the formulation of colloidal systems that could act as drug carriers into the brain.

Physisorbed o-carborane onto lyso-phosphatidylcholine-functionalized, single-walled carbon nanotubes: a potential carrier system for the therapeutic delivery of boron.

A combination of data from ICP-MS, Raman spectroscopy, UV-vis spectrometry, atomic force microscopy, zeta-potential measurements and gel electorphoresis studies has shown that o-carborane may be immobilized on stable aqueous dispersions of lyso-phosphatidylcholine-functionalized single-walled carbon nanotubes, which in turn indicates the potential of such structures for deployment as carrier vehicles in boron neutron capture therapy.

The potential for nanoparticle-based drug delivery to the brain: overcoming the blood-brain barrier.

The development of blood-brain barrier (BBB)-targeting technologies is a very active field of research: targeting therapeutic actives to the central nervous system by means of systemic administration means crossing the BBB, and this is now one of the most challenging problems in drug development. The BBB is a unique regulatory system that protects the brain environment by separating it from direct contact with the circulating blood. In doing so, it impedes at the same time the access of a large number of diagnostic and therapeutic agents into the brain parenchyma.