Remote loading in liposome: a review of current strategies and recent developments.

Liposomes have gained prominence as nanocarriers in drug delivery, and the number of products in the market is increasing steadily, particularly in cancer therapeutics. Remote loading of drugs in liposomes is a significant step in the translation and commercialization of the first liposomal product. Low drug loading and drug leakage from liposomes is a translational hurdle that was effectively circumvented by the remote loading process.

Unmet technological demands in orodispersible films for age-appropriate paediatric drug delivery.

Age-appropriateness of a formulation is the ability to deliver variable but accurate doses to the paediatric population in a safe and acceptable manner to improve medical adherence and reduce medication errors. Paediatric drug delivery is a challenging area of formulation research due to the existing gap in knowledge. This includes the unknown safety of excipients in the paediatric population, the need for an age-appropriate formulation, the lack of an effective taste-masking method and the lack of paediatric pharmacokinetic data and patient acceptability.

Role of Permeability on the Biopredictive Dissolution of Amorphous Solid Dispersions.

An ideal dissolution test for amorphous solid dispersions (ASDs) should reflect physicochemical, physiological, and hydrodynamic conditions which accurately represent in vivo dissolution. However, this is confounded by the evolution of different molecular and colloidal species during dissolution, generating a supersaturated state of the drug. The supersaturated state of a drug is thermodynamically unstable which drives the process of precipitation resulting in a loss of solubility advantage.

Fourier Transform Infrared (FTIR) Spectroscopy, Ultraviolet Resonance Raman (UVRR) Spectroscopy, and Atomic Force Microscopy (AFM) for Study of the Kinetics of Formation and Structural Characterization of Tau Fibrils.

Kinetic studies of tau fibril formation in vitro most commonly employ spectroscopic probes such as thioflavinT fluorescence and laser light scattering or negative stain transmission electron microscopy. Here, I describe the use of Fourier transform infrared (FTIR) spectroscopy, ultraviolet resonance Raman (UVRR) spectroscopy, and atomic force microscopy (AFM) as complementary probes for studies of tau aggregation. The sensitivity of vibrational spectroscopic techniques (FTIR and UVRR) to secondary structure content allows for measurement of conformational changes that occur when the intrinsically disordered protein tau transforms into cross-β-core containing fibrils.

Resonance Raman spectroscopic measurements delineate the structural changes that occur during tau fibril formation.

The aggregation of the microtubule-associated protein, tau, into amyloid fibrils is a hallmark of neurodegenerative diseases such as the tauopathies and Alzheimer's disease. Since monomeric tau is an intrinsically disordered protein and the polymeric fibrils possess an ordered cross-β core, the aggregation process is known to involve substantial conformational conversion besides growth. The aggregation mechanism of tau in the presence of inducers such as heparin, deciphered using probes such as thioflavin T/S fluorescence, light scattering, and electron microscopy assays, has been shown to conform to ligand-induced nucleation-dependent polymerization.

Difference in fibril core stability between two tau four-repeat domain proteins: a hydrogen-deuterium exchange coupled to mass spectrometry study.

One of the signatures of Alzheimer's disease and tauopathies is fibrillization of the microtubule-associated protein tau. The purpose of this study was to compare the high-resolution structure of fibrils formed by two different tau four-repeat domain constructs, tau4RD and tauK18, using hydrogen-deuterium exchange coupled to mass spectrometry as a tool. While the two fibrils are found to be constructed on similar structural principles, the tauK18 fibril has a slightly more stable core.

Mechanistic studies unravel the complexity inherent in tau aggregation leading to Alzheimer's disease and the tauopathies.

The aggregation of the protein tau into amyloid fibrils is known to be involved in the causation of the neurodegenerative tauopathies and the progression of cognitive decline in Alzheimer's disease. This review surveys the mechanism of tau aggregation with special emphasis on the information obtained from biochemical and biophysical studies. First, tau is described from a structure-function perspective.

Evidence for the existence of a secondary pathway for fibril growth during the aggregation of tau.

The mechanism of amyloid fibril formation by proteins has been classically described by the nucleation-dependent polymerization (NDP) model, which makes certain predictions regarding the kinetics of fibrillation. All proteins whose aggregation conforms to the NDP model display a t(2) time dependence for their initial reaction profile. However, there are proteins whose aggregation reactions have kinetic signatures of a flat lag phase followed by an exponential rise in fibril mass, which does not conform to the NDP model.

Understanding the kinetic roles of the inducer heparin and of rod-like protofibrils during amyloid fibril formation by Tau protein.

The aggregation of the natively disordered protein, Tau, to form lesions called neurofibrillary tangles is a characteristic feature of several neurodegenerative tauopathies. The polyanion, heparin, is commonly used as an inducer in studies of Tau aggregation in vitro, but there is surprisingly no comprehensive model describing, quantitatively, all aspects of the heparin-induced aggregation reaction. In this study, rate constants and extents of fibril formation by the four repeat domain of Tau (Tau4RD) have been reproducibly determined over a full range of heparin and protein concentrations.

Effects of diallyl disulfide (DADS) on expression of apoptosis associated proteins in androgen independent human prostate cancer cells (PC-3).

Prostate cancer is a leading cause of death among the aging men. Surgical or radiotherapy is effective when the cancer is confined to the prostate gland but once the cancer spreads beyond the pelvis even chemotherapy and hormonal ablation therapy fails in curing this disease. Our previous studies have shown that diallyl disulfide (DADS) induces cell cycle arrest and also induces apoptosis in PC-3 cells.