Chitosan non-particulate vaccine delivery systems.

Chitosan is an extensively used polymer for drug delivery applications in particulate and non-particulate carriers. Chitosan-based particulate, nano-, and microparticle, carriers have been the most extensively studied for the delivery of therapeutics and vaccines. However, chitosan has also been used in vaccine applications for its adjuvant properties in various hydrogels or as a carrier coating material.

Solid Lipid Nanoparticles for Pulmonary Delivery of Biopharmaceuticals: A Review of Opportunities, Challenges, and Delivery Applications.

Biopharmaceuticals such as nucleic acids, proteins, and peptides constitute a new array of treatment modalities for chronic ailments. Invasive routes remain the mainstay of administering biopharmaceuticals due to their labile nature in the biological environment. However, it is not preferred for long-term therapy due to the lack of patient adherence and clinical suitability.

Review of Novel Oral Amphotericin B Formulations for the Treatment of Parasitic Infections.

Amphotericin B (AmpB) is a polyene macrolide antibiotic used in the treatment of blood-borne parasitic and fungal infections. However, its use, particularly in the developing world, has been limited by dose-dependent kidney toxicity, other systemic-related toxicity issues following injection, the inconvenience of parenteral administration, and accessibility. Oral formulation approaches have focused on the dual problem of solubility and permeability of AmpB, which is poorly water soluble, amphoteric and has extremely low oral bioavailability.

Assessing the Effectiveness of Cationic Lipid Nanoparticles with a Triple Adjuvant for Intranasal Vaccination against the Respiratory Pathogen .

Continuous outbreaks of pertussis around the world suggest inadequate immune protection in infants and weakened immune responses induced over time by the acellular pertussis vaccine. Vaccine adjuvants provide a means to improve vaccine immunogenicity and support long-term adaptive immunity against pertussis. An acellular pertussis vaccine was prepared with pertactin, pertussis toxin, and fimbriae 2/3 antigens combined with a triple-adjuvant system consisting of innate defense regulator peptide IDR 1002, a Toll-like receptor-3 agonist poly(I:C), and a polyphosphazene in a fixed combination.

Chitosan Nanoparticles at the Biological Interface: Implications for Drug Delivery.

The unique properties of chitosan make it a useful choice for various nanoparticulate drug delivery applications. Although chitosan is biocompatible and enables cellular uptake, its interactions at cellular and systemic levels need to be studied in more depth. This review focuses on the various physical and chemical properties of chitosan that affect its performance in biological systems.

Evaluation of La(XT), a novel lanthanide compound, in an OVX rat model of osteoporosis.

Purpose: The purpose of this study was to evaluate the efficacy and toxicity of a novel lanthanum compound, La(XT), in an ovariectomized (OVX) rat model of osteoporosis.

Methods: Twenty-four ovariectomized female Sprague Dawley rats were divided into 3 groups receiving a research diet with/without treatment compounds (alendronate: 3 mg/kg; La(XT) 100 mg/kg) for three months. At the time of sacrifice, the kidney, liver, brain, lung and spleen were collected for histological examination.

Assessing the Safety, Tolerability, Pharmacokinetics, and Biodistribution of Novel Oral Formulations of Amphotericin B following Single- and Multiple-Dose Administration to Beagle Dogs.

The purpose of this study was to assess the safety, tolerability, pharmacokinetics (PK), and biodistribution of novel oral amphotericin B (AmpB) formulations following single- and multiple-oral-dose administration to healthy beagle dogs. The liquid formulation of AmpB was administered to three male dogs, and the capsule formulations of AmpB were administered to each of two groups of six male dogs. Blood was collected for pharmacokinetic evaluation on days 1, 2, and 3 (up to 72 h postdosing).

Safety, Tolerability, and Pharmacokinetics of a Novel Oral Amphotericin B Formulation (iCo-019) following Single-Dose Administration to Healthy Human Subjects: an Alternative Approach to Parenteral Amphotericin B Administration.

This study evaluated the safety, tolerability, and pharmacokinetics of a novel oral amphotericin B (AmB) formulation (iCo-019) following single doses to healthy humans. The data from this study suggest that iCo-019 has a long circulation time and systemic exposure without the associated gastrointestinal, liver, and kidney toxicity associated with AmB. This novel oral AmB formulation can serve as a new treatment strategy to overcome the limitations of the use of parenterally administered AmB products.

Development of a UV-Stabilized Topical Formulation of Nifedipine for the Treatment of Raynaud Phenomenon and Chilblains.

Raynaud's Phenomenon is a vascular affliction resulting in pain and blanching of the skin caused by excessive and prolonged constriction of arterioles, usually due to cold exposure. Nifedipine is a vasodilatory calcium channel antagonist, which is used orally as the first-line pharmacological treatment to reduce the incidence and severity of attacks when other interventions fail to alleviate the condition and there is danger of tissue injury. Oral administration of nifedipine, however, is associated with systemic adverse effects, and thus topical administration with nifedipine locally to the extremities would be advantageous.

Investigation into spinal anesthetic failure with hyperbaric bupivacaine: the role of cold exposure on bupivacaine degradation.

Purpose: Hyperbaric bupivacaine (0.75% in dextrose) is used for spinal obstetric anesthesia. Occasional clusters of anesthetic failures occur in this setting, not readily attributable to clinical factors.

The Development of Oral Amphotericin B to Treat Systemic Fungal and Parasitic Infections: Has the Myth Been Finally Realized?

Parenteral amphotericin B has been considered as first-line therapy in the treatment of systemic fungal and parasitic infections, however its use has been associated with a number of limitations including affordability, accessibility, and an array of systemic toxicities. Until very recently, it has been very challenging to develop a bioavailable formulation of amphotericin B due to its physical chemical properties, limited water and lipid solubility, and poor absorption. This perspective reviews several novel oral Amphotericin B formulations under development that are attempting to overcome these limitations.

A lipidic delivery system of a triple vaccine adjuvant enhances mucosal immunity following nasal administration in mice.

We previously developed an highly efficacious combination adjuvant comprised of innate defense regulator (IDR)-1002 peptide, poly(I:C) and polyphosphazene (TriAdj). Here we aimed to design and test the in vivo efficacy of a mucoadhesive nasal formulation of this adjuvant. To determine the physical properties of the formulation, the effect of addition of each individual component was characterised by gel electrophoresis and fluorescence quenching using rhodamine-poly(I:C).

Development and in vitro characterization of chitosan-coated polymeric nanoparticles for oral delivery and sustained release of the immunosuppressant drug mycophenolate mofetil.

Objective: To develop an oral sustained release formulation of mycophenolate mofetil (MMF) for once-daily dosing, using chitosan-coated polylactic acid (PLA) or poly(lactic-co-glycolic) acid (PLGA) nanoparticles. The role of polymer molecular weight (MW) and drug to polymer ratio in encapsulation efficiency (EE) and release from the nanoparticles was explored in vitro.

Methods: Nanoparticles were prepared by a single emulsion solvent evaporation method where MMF was encapsulated with PLGA or PLA at various polymer MW and drug: polymer ratios.

Scavenger receptor class BI (SR-BI) mediates uptake of CPX-351 into K562 leukemia cells.

Purpose: CPX-351 is a liposomal formulation of cytarabine and daunorubicin encapsulated at a 5:1 molar ratio, for the treatment of acute myeloid leukemia. The Scavenger Receptor class B type I (SR-BI) plays an important role in mediating the uptake of high-density lipoproteins. The purpose of this study is to assess the role of the cell surface lipoprotein receptor SR-BI in the uptake of CPX-351 liposomes (Jazz Pharmaceuticals) into K562 leukemia cells.

An Overview of Chitosan Nanoparticles and Its Application in Non-Parenteral Drug Delivery.

The focus of this review is to provide an overview of the chitosan based nanoparticles for various non-parenteral applications and also to put a spotlight on current research including sustained release and mucoadhesive chitosan dosage forms. Chitosan is a biodegradable, biocompatible polymer regarded as safe for human dietary use and approved for wound dressing applications. Chitosan has been used as a carrier in polymeric nanoparticles for drug delivery through various routes of administration.

Review and analysis of FDA approved drugs using lipid-based formulations.

Lipid-based drug delivery systems (LBDDS) are one of the most studied bioavailability enhancement technologies and are utilized in a number of U.S. Food and Drug Administration (FDA) approved drugs.

Bone-seeking agents for the treatment of bone disorders.

The targeting and delivery of therapeutic and diagnostic agents to bone tissue presents both a challenge and opportunity. Osteoporosis, Paget's disease, cancer, and bone metastases are all skeletal diseases whose treatment would benefit from new targeted therapeutic strategies. Osteoporosis, in particular, is a very prevalent disease, affecting over one in three women and one in five men in Canada alone with the cost to the healthcare system estimated at over $2.

La(iii) biodistribution profiles from intravenous and oral dosing of two lanthanum complexes, La(dpp) and La(XT), and evaluation as treatments for bone resorption disorders.

Trivalent lanthanum (La) has the potential to treat bone resorption disorders (such as osteoporosis) by eliciting a bone-building response in the cells which control skeletal remodelling. Because La suffers from extremely poor intestinal absorption, specifically designed chelators are required in order that a biologically active form of lanthanum can be administered orally. Two such chelators, 1,2-dimethyl-3-hydroxy-4-pyridinone (Hdpp) and bis-{[bis(carboxymethyl)amino]methy}phosphinic acid (HXT), have previously been the subjects of extensive physical, in vitro, and in vivo testing as the tris- and mono-lanthanum(iii) complexes La(dpp) and La(XT), respectively.

Lipid-lowering Activity of Natural and Semi-Synthetic Sterols and Stanols.

Consumption of plant sterols/ stanols has long been demonstrated to reduce plasma cholesterol levels. The objective of this review is to demonstrate the lipid-lowering activity and anti-atherogenic effects of natural and semi-synthetic plant sterols/ stanols based on evidence from cell-culture studies, animal studies and clinical trials. Additionally, this review highlights certain molecular mechanisms by which plant sterols/ stanols lower plasma cholesterol levels with a special emphasis on factors that affect the cholesterol-lowering activity of plant sterols/stanols.

Novel oral amphotericin B formulation (iCo-010) remains highly effective against murine systemic candidiasis following exposure to tropical temperature.

Purpose: To evaluate the antifungal activity of amphotericin B (AmB) in a mouse model of systemic candidiasis following administration of a novel oral AmB formulation (iCo-010) that has been pre-exposed to tropical temperatures.

Methods: Amphotericin B (AmB) was prepared as a 5 mg/mL dispersion in a mixture of Peceol, Gelucire 44/14 and VitE-TPGS 2,3 (iCo-010). The formulation was protected from light and incubated in a sealed container at 43 °C for 60 days.

Efficacy of an oral and tropically stable lipid-based formulation of Amphotericin B (iCo-010) in an experimental mouse model of systemic candidiasis.

Objective: An oral lipid based formulation that exhibits tropical stability (iCo-010) was developed to enhance the absorption of orally administered amphotericin B (AmB). iCo-010 has previously shown high efficacy in an acute model of systemic candidiasis in rats, directing the focus of this study to be its efficacy in a chronic model of systemic candidiasis in mice.

Methods: Mice were infected with 0.

Pharmacokinetics and tissue distribution of amphotericin B following oral administration of three lipid-based formulations to rats.

The objective of this study was to assess the pharmacokinetics and tissue distribution of amphotericin B (AmB) in rats following oral administration of three lipid-based formulations (iCo-009, iCo-010 and iCo-011). The lipid-based formulations were administered to rats at a dose of 10 mg/kg and blood samples were withdrawn at predose, 1, 2, 4, 6, 8, 10, 12, 24, 48 and 72 h, after which the animals were sacrificed and the body organs were collected for AmB quantification using a validated HPLC method. Plasma pharmacokinetics parameters were determined using non-compartmental analysis.

Efficacy and toxicity of a tropically stable lipid-based formulation of amphotericin B (iCo-010) in a rat model of invasive candidiasis.

The objective of this work was to assess the antifungal activity of a tropically stable formulation of amphotericin B (AmB) (iCo-010) over short period of treatment in a rat model of invasive candidiasis. The rats were infected with Candida albicans (ATCC 18804); 48 h later, the animals were assigned either to a control group, AmBisome(®) group (5 mg/kg QD), or iCo-010 groups (0.5, 1, 2.

Assessment of novel oral lipid-based formulations of amphotericin B using an in vitro lipolysis model.

The purpose of this study was to investigate the intraluminal processing of novel oral lipid-based formulations of amphotericin B using an in vitro lipolysis model. Amphotericin B (AmB) was formulated in three lipid-based formulations consisting of different lipid components: iCo-009, iCo-010 and iCo-011. Various lipid loads (0.

In vitro cytotoxicity of two novel oral formulations of Amphotericin B (iCo-009 and iCo-010) against Candida albicans, human monocytic and kidney cell lines.

Background: Invasive fungal infections such as candidiasis constitute an increasingly important medical problem. Drugs currently used for the treatment of candidiasis include polyenes (such as Amphotericin B) and azoles. Amphotericin B (AmpB) presents several limitations such as its nephrotoxicity and limited solubility.