Lipid nanoparticles for enhancing oral bioavailability.

In recent studies, lipid nanoparticles have attracted attention as drug delivery systems owing to their preeminent potential in achieving the desired bioavailability of biopharmaceutics (BCS) class II and class IV drugs. The current debate concerns the bioavailability of these poorly absorbed drugs with their simultaneous oral degradation. Lipid nanoparticles, including solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), are lipid-based carrier systems that can effectively encapsulate both lipophilic and hydrophilic drugs, offering versatile drug delivery systems.

Role of rheology in formulation and process design of hot melt extruded amorphous solid dispersions.

Hot melt extrusion (HME) has been widely used as a continuous and highly flexible pharmaceutical manufacturing process for the production of a variety of dosage forms. In particular, HME enables preparation of amorphous solid dispersions (ASDs) which can improve bioavailability of poorly water-soluble drugs. The rheological properties of drug-polymer mixtures can significantly influence the processability of drug formulations via HME and eventually the end-use product properties such as physical stability and drug release.

The Effect of Process Parameters on the Microstructure, Stability, and Sensorial Properties of an Emulsion Cream Formulation.

A classical emulsion formulation based on petrolatum and mineral oil as the internal phase with emulsifier wax as a typical topical emulsion cream was investigated for the effect of process parameters on drug product quality and performance attributes. The Initial Design of Experiment (DoE) suggested that an oil phase above 15%, coupled with less than 10% emulsifying wax, resulted in less stable emulsions. Different processing parameters such as homogenization speed, duration, cooling rate, and final temperature showed minimal influence on properties and failed to improve stability.

Topical drug delivery by Sepineo P600 emulgel: Relationship between rheology, physical stability, and formulation performance.

The objective of this present work was to develop and optimize oil-in-water (O/W) emulsion-based gels, namely emulgels that allow maximum topical drug delivery while having desired microstructure and acceptable physical stability. Emulgels containing 2.0 wt% lidocaine were prepared using various concentrations (0.

Sustainable Alternatives to Petroleum-Derived Excipients in Pharmaceutical Oil-in-Water Creams.

Recently, vast efforts towards sustainability have been made in the pharmaceutical industry. In conventional oil-in-water (O/W) cream formulations, various petroleum-based excipients, namely mineral oil and petrolatum, are commonly used. Natural or synthetic excipients, derived from vegetable sources, were explored as alternatives to petroleum-based excipients in prototype topical creams, with 1% (w/w) lidocaine.

Influence of Manufacturing Process on the Microstructure, Stability, and Sensorial Properties of a Topical Ointment Formulation.

The manufacturing process for ointments typically involves a series of heating, cooling, and mixing steps. Precise control of the level of mixing through homogenization and the cooling rate, as well as temperature at different stages, is important in delivering ointments with the desired quality attributes, stability, and performance. In this work, we investigated the influence of typical plant processing conditions on the microstructure, stability, and sensorial properties of a model ointment system through a Design of Experiments (DoE) approach.

Topical Administration of an Apoptosis Inducer Mitigates Bleomycin-Induced Skin Fibrosis.

Pathological fibrosis is distinguished from physiological wound healing by persistent myofibroblast activation, suggesting that therapies that induce myofibroblast apoptosis selectively could prevent progression and potentially reverse the established fibrosis, such as for scleroderma (a heterogeneous autoimmune disease characterized by multiorgan fibrosis). Navitoclax (NAVI) is a BCL-2/BCL-xL inhibitor with antifibrotic properties and has been investigated as a potential therapeutic for fibrosis. NAVI makes myofibroblasts particularly vulnerable to apoptosis.

Assessing and Predicting Physical Stability of Emulsion-Based Topical Semisolid Products: A Review.

The emulsion-based topical semisolid dosage forms present a high degree of complexity due to their microstructures which is apparent from their compositions comprising at least two immiscible liquid phases, often times of high viscosity. These complex microstructures are thermodynamically unstable, and the physical stability of such preparations is governed by formulation parameters such as phase volume ratio, type of emulsifiers and their concentration, HLB value of the emulsifier, as well as by process parameters such as homogenizer speed, time, temperature etc. Therefore, a detailed understanding of the microstructure in the DP and critical factors that influence the stability of emulsions is essential to ensure the quality and shelf-life of emulsion-based topical semisolid products.

API-polymer interactions in Sepineo P600 based topical gel formulation- impact on rheology.

In the present study, topical gel and emulsion gel were formulated using Acrylamide/ Sodium Acryloyldimethyl taurate copolymer (Sepineo P600) as a gelling agent, and their rheological attributes and physical stability were evaluated upon incorporation of API. Lidocaine, a free base drug (pK 7.92) was used as a model drug in all formulations.

Nano-Vesicle Based Anti-Fungal Formulation Shows Higher Stability, Skin Diffusion, Biosafety and Anti-Fungal Efficacy In Vitro.

Opportunistic fungal infections are responsible for over 1.5 million deaths per year. This has created a need for highly effective antifungal medication to be as potent as possible.

Polymers for Extrusion-Based 3D Printing of Pharmaceuticals: A Holistic Materials-Process Perspective.

Three dimensional (3D) printing as an advanced manufacturing technology is progressing to be established in the pharmaceutical industry to overcome the traditional manufacturing regime of 'one size fits for all'. Using 3D printing, it is possible to design and develop complex dosage forms that can be suitable for tuning drug release. Polymers are the key materials that are necessary for 3D printing.

Engineered Nanodelivery Systems to Improve DNA Vaccine Technologies.

DNA vaccines offer a flexible and versatile platform to treat innumerable diseases due to the ease of manipulating vaccine targets simply by altering the gene sequences encoded in the plasmid DNA delivered. The DNA vaccines elicit potent humoral and cell-mediated responses and provide a promising method for treating rapidly mutating and evasive diseases such as cancer and human immunodeficiency viruses. Although this vaccine technology has been available for decades, there is no DNA vaccine that has been used in bed-side application to date.

Thermoresponsive nanoemulsion-based gel synthesized through a low-energy process.

Thermoresponsive nanoemulsions find utility in applications ranging from food to pharmaceuticals to consumer products. Prior systems have found limited translation to applications due to cytotoxicity of the compositions and/or difficulties in scaling-up the process. Here, we report a route to thermally gel an oil-in-water nanoemulsion using a small amount of FDA-approved amphiphilic triblock Pluronic copolymers which act as gelling agents.

M cell targeting engineered biomaterials for effective vaccination.

Vaccines are one of the greatest medical interventions of all time and have been successful in controlling and eliminating a myriad of diseases over the past two centuries. Among several vaccination strategies, mucosal vaccines have wide clinical applications and attract considerable interest in research, showing potential as innovative and novel therapeutics. In mucosal vaccination, targeting (microfold) M cells is a frontline prerequisite for inducing effective antigen-specific immunostimulatory effects.

A General Route for Nanoemulsion Synthesis Using Low-Energy Methods at Constant Temperature.

The central dogma of nanoemulsion formation using low-energy methods at constant temperature-popularly known as the emulsion inversion point (EIP) method-is that to create O/W nanoemulsions, water should be added to a mixture of an oil and surfactant. Here, we demonstrate that the above order of mixing is not universal and a reverse order of mixing could be superior, depending on the choice of surfactant and liquid phases. We propose a more general methodology to make O/W as well as W/O nanoemulsions by studying the variation of droplet size with the surfactant hydrophilic-lypophilic balance for several model systems.

3D printing of self-assembling thermoresponsive nanoemulsions into hierarchical mesostructured hydrogels.

Spinodal decomposition and phase transitions have emerged as viable methods to generate a variety of bicontinuous materials. Here, we show that when arrested phase separation is coupled to the time scales involved in three-dimensional (3D) printing processes, hydrogels with multiple length scales spanning nanometers to millimeters can be printed with high fidelity. We use an oil-in-water nanoemulsion-based ink with rheological and photoreactive properties that satisfy the requirements of stereolithographic 3D printing.

Core-Shell Composite Hydrogels for Controlled Nanocrystal Formation and Release of Hydrophobic Active Pharmaceutical Ingredients.

Although roughly 40% of pharmaceuticals being developed are poorly water soluble, this class of drugs lacks a formulation strategy capable of producing high loads, fast dissolution kinetics, and low energy input. In this work, a novel bottom-up approach is developed for producing and formulating nanocrystals of poorly water-soluble active pharmaceutical ingredients (APIs) using core-shell composite hydrogel beads. Organic phase nanoemulsion droplets stabilized by polyvinyl alcohol (PVA) and containing a model hydrophobic API (fenofibrate) are embedded in the alginate hydrogel matrix and subsequently act as crystallization reactors.

β-Cyclodextrin conjugated magnetic, fluorescent silica core-shell nanoparticles for biomedical applications.

We present synthesis of highly uniform magnetic nanocomposite material possessing an assortment of important functionalities: magnetism, luminescence, cell-targeting, and hydrophobic drug delivery. Magnetic particle Fe3O4 is encapsulated within a shell of SiO2 that ensures biocompatibility of the nanocomposite as well as act as a host for fluorescent dye (FITC), cancer-targeting ligand (folic acid), and a hydrophobic drug storage-delivering vehicle (β-cyclodextrin). Our preliminary results suggest that such core-shell nanocomposite can be a smart theranostic candidate for simultaneous fluorescence imaging, magnetic manipulation, cancer cell-targeting and hydrophobic drug delivery.