Evaluation of the Intestinal Colonizing Potential and Immunomodulating Capacity of Lactobacilli Microspheres.

Lactobacilli species get degraded by acidic conditions in the stomach. Thus, the objective of this study was to (1) formulate and characterize gastro-resistant Lactobacilli microspheres and (2) evaluate the ability of Lactobacilli microspheres to colonize the intestine and their capacity to have an immunomodulating effect in vivo. The product yield and the encapsulation efficiency were 45% and 100%, respectively. The average microsphere particle size was 5 µm. Lactobacilli microspheres were most stable at 4°C and showed a better suspendibility in distilled water. Without encapsulation, the viability of bacteria decreased within 30 min. In the case of Lactobacilli microspheres, no Lactobacilli were released in the first 3 h, and highest release was observed at 4 h, thus, suggesting the significance of encapsulation of Lactobacilli. Lactobacilli microspheres maintained intestinal colonization only during the dosing period, and the serum IgG, serum IgA, fecal, intestinal, nasal IgA, and the serum interleukin-1ß levels were higher in the Lactobacilli microsphere group compared with the blank microsphere and the lactobacilli solution group, suggesting that the Lactobacilli microspheres were more gastro-resistant and, hence, showed positive effects compared with the Lactobacilli solution. However, the Lactobacilli microspheres did not have a significant effect on the tumor necrosis factor-α levels.

Solid Matrix Based Lipidic Nanoparticles in Oral Cancer Chemotherapy: Applications and Pharmacokinetics.

Chemotherapeutic delivery by oral route in cancer patients has the potential to create "hospitalization free chemotherapy" which is a vision of oncologists, formulation scientists and patients. Such a therapeutic approach will improve patients' compliance, ease the burden of the patients' caregivers and significantly reduce the cost of treatment. In current clinical practice, chemotherapy carried out by intravenous injection or infusion leads to undesired side-effects such as plasma concentrations crossing the maximum safe concentration, rapid body clearance and lower bioavailability. Despite the presence of challenges such as poor aqueous solubility and stability of drugs and the presence of biological barriers like multidrug efflux transporter in the GI tract, oral cancer chemotherapy has the potential to surmount those obstacles. Lipid nanoparticles (LNPs) such as solid lipid nanoparticle, nanostructured lipid carriers, nano lipid-drug conjugates, mixed micelles, liposomes and nanoemulsions have shown some promising results for use in oral anticancer drug delivery through nanotechnological approach. LNPs demonstrate enhanced oral bioavailability owing to their ability to inhibit first pass metabolism via lymphatic absorption by chylomicron-linked and/or M-cell uptake. LNPs reduce the inter- and intrasubject pharmacokinetics variability of administrated drugs. Moreover, certain classes of phospholipids and surfactants used in the formulations of LNPs can suppress the P-glycoprotein efflux system. Here, we shall be discussing the biopharmaceutical challenges in oral cancer chemotherapy and how the LNPs may provide solutions to such challenges. The effect of GI tract environment on LNPs and pharmacokinetics shall also be discussed.

Emerging advances in cancer nanotheranostics with graphene nanocomposites: opportunities and challenges.

As an inorganic nanomaterial, graphene nanocomposites have gained much attention in cancer nanotechnology compared with the other inorganic nanomaterial in recent times. Although a relatively new drug carrier, it has been extensively explored as a potential chemotherapeutic carrier and theranostic because of its numerous physicochemical properties, including, capability of multiple pay load, functionalization for drug targeting and photothermal effect. Despite potential benefit, its translation from bench to bed-side in cancer therapy is challenged due to its toxicity concern. Here, we discussed the present progress and future possibilities of graphene nanocomposites as a cancer theranostic. Moreover, the paper also exemplifies the effects of graphene/graphene oxide on tissues and organ functions in order to understand the extent and mechanism of toxicity.

The effect of antisense to NF-κB in an albumin microsphere formulation on the progression of left-ventricular remodeling associated with chronic volume overload in rats.

BACKGROUND: Increased NF-κB levels play a crucial role in the pathophysiology of heart failure and are known to cause ventricular remodeling. Antisense therapy can be used for blocking the expression of NF-κB and subsequently avoiding heart failure. However, as with most biotechnology products, molecular instability and overall cost are often the major issues and concerns limiting the advancement of most antisense drugs to the market. Therefore, a cost-efficient biodegradable sustained release particle drug delivery system to transport and target NF-kB antisense to its intended site of action would be ideal. PURPOSE: To evaluate the in vivo performance of a sustained release spray-dried albumin microsphere formulation for effective delivery and treatment of left ventricular remodeling with antisense to NF-κB. METHODS: Albumin-based microspheres encapsulating antisense to NF-kB were prepared by spray drying and studied in a rat model to treat congestive heart failure. RESULTS: The NF-κB activation and TNF-α release seen in treated animals were significantly lower than control animals. Ventricular remodeling was controlled in animals with antisense-treated AV fistulas as ΔV0-25 and ΔV0 were significantly lower compared to animals with untreated AV fistulas. CONCLUSION: This treatment was successful in curbing ventricular remodeling by suppressing NF-κB activation.

In vitro and ex vivo characterization of lectin-labeled Mycobacterium tuberculosis antigen-containing microspheres for enhanced oral delivery.

PURPOSE: Oral immunization for mucosal protection against Mycobacterium tuberculosis would be the best option for effective tuberculosis (TB) control. However, this route of vaccine delivery is limited due to the short residence time of the delivery system at the site of absorption. Cytoadhension has made it possible to optimize the targeted delivery of oral vaccine to lymphoid tissues. The purpose of this project was to evaluate the ability of human M-cell specific lectin-labeled microparticles to target the human M-cells of the Peyer's patches. METHOD: Albumin microspheres containing Mycobacterium tuberculosis cell lysate antigens were coupled with Wheat germ agglutinin and Aleuria aurantia lectins and their ability to bind to M cell models as well as their preferential distribution in the Peyer's patches were investigated. RESULTS: The study demonstrated an enhanced delivery of targeted polystyrene and BSA/Lysate microspheres to M cells. It was demonstrated that alpha-l-fucose sugar residue might be the target of these lectins. CONCLUSION: It can be concluded from the study that the lectin-coupled microspheres had better affinity for M-cells and showed preferential binding to the Peyer's patches. This means that the coupling enhanced the targeted delivery of the antigens to the M cells.

Formulation, characterization and testing of tetracaine hydrochloride-loaded albumin-chitosan microparticles for ocular drug delivery.

Most ocular surgical procedures take approximately 60 min to complete, the anaesthetic property of the safest drug, tetracaine, is initiated in a few minutes and lasts approximately 10-15 min. The purpose of the present study was to develop an ocular tetracaine formulation which can produce an immediate onset of action and/or longer duration of action during the entire surgical procedure. Tetracaine-loaded microparticle formulation was prepared by the method of spray-drying and characterized in terms of size, zeta potential, morphology, thermal stability and release pattern. The study reports a microparticulate ocular formulation with minimum cytotoxicity and optimum cellular uptake. In addition, microencapsulated tetracaine was found to significantly increase the duration of action of the drug up to 4-fold. Taken together, the results presented in this work described albumin-chitosan microparticles to be an effective delivery platform for ocular anaesthetic agents and a potential treatment of various ocular diseases.