APPLICATION OF POLYMERIC NANOPARTICLES IN IMMUNOTHERAPY

Purpose of review The purpose of the present review is to underline the importance of nanoparticulate carriers, such as polymeric nanoparticles, in the future development of safe and effective formulation in the field of immunotherapy against infectious diseases and cancer. Recent findings Polymeric nanoparticles can modulate the immune response, that is, by targeting antigens to dendritic cells that possess a crucial role in initiating immune responses, and might be potentially useful in immunotherapy. Summary In the last decades, significant progress in research and clinics has been made to offer possible innovative therapeutics for the management of infectious diseases and cancer. Polymeric nanoparticles are particularly adept at facilitating immunotherapeutic approaches because they can be engineered to have different physical properties, encapsulated agents, and surface ligands. Moreover, these systems are administrable for all routes, are capable of being actively taken up by dendritic cells and have shown promising potential in systemic and mucosal immunotherapy. Here, some recent findings on these systems, in their potential applications for infectious and cancer immunotherapy, are reported

THERAPEUTIC-LOADED LIPID NANOSTRUCTURES AND BRAIN DISEASES.

Central Nervous System (CNS) diseases represent the largest and fastest growing area of unmet medical need since an alarming increase in brain disease incidence is going on. Despite major advances in neuroscience, many potential therapeutic agents are denied access to the CNS because of the existence of a physiological low permeable barrier, the Blood-Brain Barrier (BBB). To obtain an improvement of drug CNS performance, sophisticated approaches such as nanoparticulate systems are rapidly developing. In particular, in this chapter, the most recent data demonstrating the potential of lipid nanostructures, such as Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC), to transport drugs successfully into the brainfor the treatment of CNS diseases including Alzheimer’s and Parkinson’s diseases, cancer, mood disorder, AIDS, and bacterial infections, are summarised. Their use as drug delivery systems is associated with many advantages that include an excellent storage stability, a relatively easy production without the use of any organic solvent, the possibility of steam sterilization and lyophilization, and large scale production. Moreover, SLN and NLC are obtained by using physiologically well-tolerated ingredients already approved for pharmaceutical applications in humans and show low toxicity when administered. Because of their small size, these systems may be injected intravenously and avoid the uptake of macrophages of mononuclear phagocyte system (MPS). Moreover, their lipophilic features lead them to CNS by an endocytotic mechanism, overcoming the BBB

LIPID NANOPARTICLES FOR DRUG TARGETING TO THE BRAIN

In this chapter, the main production methods of lipid nanostructures such as solid lipid nanoparticles and nanostructured lipid carriers, and their application are described. In particular, we describe the strategies commonly used to obtain lipid nanoparticles to overcome the blood–brain barrier (BBB) for the treatment of several brain diseases. The use of these carriers as targeted drug delivery systems is associated with many advantages that include excellent storage stability, easy production without the use of any organic solvent, the possibility of steam sterilization and lyophilization, and large scale production. They exhibit good stability during long-term storage, consist of physiologically well-tolerated ingredients often already approved for pharmaceutical applications in humans, and are generally recognized as safe. Under optimized conditions, they can be produced to incorporate several drugs and therapeutic proteins. Formulation in solid lipidnanostructures confers improved drug loading and protein stability, targeting, and sustained release of the incorporated molecules. Moreover, their lipophilic features lead them to the central nervous system by an endocytotic mechanism, overcoming the BBB. Many drugs have been incorporated into solid lipid nanosystems and several therapeutic applications may be foreseen, such as targeting with molecules useful for treatment of brain diseases

BRAIN-TARGETED SOLID LIPID NANOPARTICLES CONTAINING RILUZOLE: PREPARATION, CHARACTERIZATION AND BIODISTRIBUTION

Aim: Developments within nanomedicine have revealed a great potential for drug delivery to the brain. In this study nanoparticulate systems as drug carriers for riluzole, with sufficiently high loading capacity and small particle size, were prepared to a reach therapeutic drug level in the brain. Materials & method: Solid lipid nanoparticles containing riluzole have great potential as drug-delivery systems for myotrophic lateral sclerosis and were produced by using the warm oil-in-water microemulsion technique. The resulting systems obtained were approximately 88 nm in size and negatively charged. Drug-release profiles demonstrated that a drug release was dependent on medium pH. Biodistribution of riluzole blended into solid lipid nanoparticles was carried out after administration to rats and the results were compared with those obtained by riluzole aqueous dispersion administration. Rats were sacrificed at time intervals of 8, 16 and 30 h, and the riluzole concentration in the blood and organs such as the brain, liver, spleen, heart and kidney was determined. Results: It was demonstrated that these solid lipid nanoparticles were able to successfully carry riluzole into the CNS. Moreover, a low drug biodistribution in organs such as the liver, spleen, heart, kidneys and lung was found when riluzole was administered as drug-loaded solid lipid nanoparticles. Conclusion: Riluzole-loaded solid lipid nanoparticles showed colloidal size and high drug loading, a greater efficacy than free riluzole in rats, a higher capability to carry the drug into the brain and a lower indiscriminate biodistribution

NANOPARTICULATE SYSTEMS FOR DRUG DELIVERY AND TARGETING TO THE CENTRAL NERVOUS SYSTEM

Brain delivery is one of the major challenges for the neuropharmaceutical industry since an alarming increase in brain disease incidence is going on. Despite major advances in neuroscience, many potential therapeutic agents are denied access to the central nervous system (CNS) because of the existence of a physiological low permeable barrier, the blood–brain barrier (BBB). To obtain an improvement of drug CNS performance, sophisticated approaches such as nanoparticulate systems are rapidly developing. Many recent data demonstrate that drugs could be transported successfully into the brain using colloidal systems after i.v. injection by several mechanisms such as endocytosis or P-glycoprotein inhibition. This review summarizes the main brain targeted nanoparticulate carriers such as liposomes, lipid nanoparticles, polymeric nanoparticles, and micelles with great potential in drug delivery into the CNS

Entrapment of an EGFR inhibitor into nanostructured lipid carriers (NLC) improves its antitumor activity against human hepatocarcinoma cells

Background: In hepatocellular carcinoma (HCC), different signaling pathways are de-regulated, and among them, the expression of the epidermal growth factor receptor (EGFR). Tyrphostin AG-1478 is a lipophilic low molecular weight inhibitor of EGFR, preferentially acting on liver tumor cells. In order to overcome its poor drug solubility and thus improving its anticancer activity, it was entrapped into nanostructured lipid carriers (NLC) by using safe ingredients for parenteral delivery. Results: Nanostructured lipid carriers (NLC) carrying tyrphostin AG-1478 were prepared by using the nanoprecipitation method and different matrix compositions. The best system in terms of mean size, PDI, zeta potential, drug loading and release profile was chosen to evaluate the anti-proliferative effect of drug-loaded NLC versus free drug on human hepatocellular carcinoma HA22T/VGH cells. Conclusions: Thanks to the entrapment into NLC systems, tyrphostin AG-1478 shows an enhanced in vitro anti-tumor activity compared to free drug. These finding raises hope of future drug delivery strategy of tyrphostin AG-1478 -loaded NLC targeted to the liver for the HCC treatment