Light-Responsive and Dual-Targeting Liposomes: From Mechanisms to Targeting Strategies.

In recent years, nanocarriers have played an ever-increasing role in clinical and biomedical applications owing to their unique physicochemical properties and surface functionalities. Lately, much effort has been directed towards the development of smart, stimuli-responsive nanocarriers that are capable of releasing their cargos in response to specific stimuli. These intelligent-responsive nanocarriers can be further surface-functionalized so as to achieve active tumor targeting in a sequential manner, which can be simply modulated by the stimuli. By applying this methodological approach, these intelligent-responsive nanocarriers can be directed to different target-specific organs, tissues, or cells and exhibit on-demand controlled drug release that may enhance therapeutic effectiveness and reduce systemic toxicity. Light, an external stimulus, is one of the most promising triggers for use in nanomedicine to stimulate on-demand drug release from nanocarriers. Light-triggered drug release can be achieved through light irradiation at different wavelengths, either in the UV, visible, or even NIR region, depending on the photophysical properties of the photo-responsive molecule embedded in the nanocarrier system, the structural characteristics, and the material composition of the nanocarrier system. In this review, we highlighted the emerging functional role of light in nanocarriers, with an emphasis on light-responsive liposomes and dual-targeted stimuli-responsive liposomes. Moreover, we provided the most up-to-date photo-triggered targeting strategies and mechanisms of light-triggered drug release from liposomes and NIR-responsive nanocarriers. Lastly, we addressed the current challenges, advances, and future perspectives for the deployment of light-responsive liposomes in targeted drug delivery and therapy.

Liquisolid Technology: A State-of-the-Art Review on the Current State, Challenges, New and Emerging Technologies for Next Generation.

Nowadays, the focus has been shifted to new technologies for improving drug solubility, permeability, and bioavailability, amid unprecedentedly increasing the number of newly discovered Active Pharmaceutical Ingredients (APIs), which are mostly categorized under Biopharmaceutical Classification System (BCS) as class-II and class IV. Traditional technologies and classical formulation strategies often fail to address most of the formulation problems associated with new APIs, particularly solubility and bioavailability. Therefore, exploring new and innovative technologies on an industrial scale is a prerequisite and requires modernization of manufacturing processes, as well as more advanced research and development. Liquisolid technology is a new, innovative industrial technology, particularly designed for either improving the release rates of poorly absorbed drugs or controlling their release pattern by achieving sustained-release profiles with zero-order release kinetics. Besides, it is a promising photoprotective system for photosensitive drugs and can further be used for modulating the drug microenvironmental pH. The next generation of liquisolid systems stems from a set of emerging technologies, such as liqui-pellet technology, which originates from combining liquisolid technology with pelletization technique, particularly extrusion-spheronization technique. This review article highlights the current state of liquisolid technology, ongoing challenges, characterization and applications, possible future prospects, the advent of new and emerging technologies, and the revolution of the next generation of liquisolid technology.

Enhancing the Intestinal Permeation of the Chondroprotective Nutraceuticals Glucosamine Sulphate and Chondroitin Sulphate Using Conventional and Modified Liposomes.

BACKGROUND: Liposomes are promising systems for the delivery of macromolecules and poorly absorbed drugs, owing to their ability to compartmentalize drugs, their biodegradability and biocompatibility. OBJECTIVE: The aim of the present study was to formulate and evaluate conventional and modified glucosamine sulphate (GluS) and chondroitin sulphate (CS) liposomal formulations, to enhance their oral permeation for the treatment of osteoarthritis (OA). METHOD: Liposomal formulations were prepared by the thin-film hydration method using two types of phospholipids; Epikuron 200© and Epikuron 200© SH, and three permeation enhancers; poloxamer 407, cetylpyridinium chloride, and sodium deoxycholate. In-vitro characterization of liposomal formulations was conducted in terms of entrapment efficiency, particle size, zeta potential, viscosity, physical stability and mucoadhesive strength. Surface morphology and vesicle shape, ex-vivo intestinal permeation, and histopathological studies were further carried out on the selected formulation. RESULTS: Results showed that the liposomal formulation containing sodium deoxycholate was the most optimum formula, showing high entrapment efficiency (60.11% for GluS and 64.10% for CS) with a particle size of 4.40 µm, zeta potential of -17.2 mV and viscosity of 2.50 cP. CONCLUSION: The aforementioned formula displayed the highest cumulative % permeated of GluS and CS through rabbit intestinal mucosa compared to the solution of drugs and other liposomal formulations (64.20% for GluS and 78.21% for CS) after 2 hours. There were no histopathological alterations in the intestinal tissue, suggesting the safety of the utilized liposomal formulation. In light of the above, liposomes can be considered promising oral permeation-enhancer system for GluS and CS, which is worthy of future bioavailability experimentation.

Geriatric-Oriented High Dose Nutraceutical ODTs: Formulation and Physicomechanical Characterization.

CONTEXT: Oral disintegrating tablets (ODTs) represent a better option than conventional tablets for geriatric population, owing to their fast onset of action and their better patient compliance. OBJECTIVE: Two principal therapeutic high-dose nutraceuticals; chondroitin sulphate and glucosamine were formulated into an oral disintegration tablet (ODT) intended for sublingual administration, and optimized to improve compliance and achieve rapid onset of action in osteoarthritis treatment. MATERIALS AND METHODS: Different formulations were prepared either by melt granulation or direct compression techniques. Excipients at different ratios such as superdisintegrants, pharmaburst™ C1, spray-dried mannitol, and polyethylene glycols were used to enhance the disintegration time for the ODT systems. RESULTS: Although the ODT systems weighed around 1.3 gm with 60% drug load, some systems disintegrated within 2-3 min with 100% drug release. Pharmaburst™ C1 turned out to be the key excipient responsible for the superdisintegration properties of the ODTs. Dissolution enhancement of the two nutraceuticals could be achieved compared to the marketed conventional tablets. CONCLUSION: The improved disintegration and dissolution properties of our prepared ODTs are expected to enhance the bioavailability of the high dose glucosamine and chondroitin sulphate in comparison with conventional tablets, which delineates them as a promising dosage form for the aforementioned nutraceuticals.