Chondroitin sulfate conjugation facilitates tumor cell internalization of albumin nanoparticles for brain-targeted delivery of temozolomide via CD44 receptor-mediated targeting.

In the present investigation, temozolomide (TMZ) loaded chondroitin sulfate conjugated albumin nanoparticles (CS-TNPs) were fabricated by desolvation method were chondroitin sulfate (CS) was used as the surface exposed ligand to achieve CD44 receptor mediated targeting of brain tumor. The developed CS-TNPs were characterized for particle size, zeta potential, entrapment efficiency and drug loading and evaluated by FTIR, DSC, XRD and TEM analysis. BBB (blood brain barrier) passage study using in vitro BBB model indicated that CS-TNPs were able to efficiently cross the BBB. Cell viability assay data demonstrated higher cytotoxicity of CS-TNPs as compared with pure TMZ. The CD44 receptor blocking assay and receptor poisoning assay in U87 MG cells confirmed the CD44 receptor and endocytosis-mediated (caveolae pathway) uptake of CS-TNPs. CS-TNPs were able to generate ROS in U87 MG cells. In vivo pharmacokinetic and biodistribution studies were performed in Wistar rats. In vivo results revealed significant enhancement in pharmacokinetic profile of CS-TNPs as compared with TMZ alone. Biodistribution results demonstrated higher accumulation of TMZ in the brain by CS-TNPs as compared with the pure drug that confirmed the brain targeting ability of nanoparticles. From all obtained results, it may be concluded that CS-TNPs are promising carrier to deliver TMZ to the brain for targeted therapy of brain tumor. Graphical abstract.

Intranasal Delivery of Nanotherapeutics/ Nanobiotherapeutics for the Treatment of Alzheimer's Disease: A Proficient Approach.

Therapeutics and biotherapeutics-based fabrication of nanoparticles has fascinated scientists since the past two decades and exciting challenges have been surmounted. Particular interest has been paid to the exploitation of functionalized nanocarriers in the treatment of Alzheimer's disease (AD) using nasal route. Development of various material-based nanocarriers is a common approach to obtain advanced drug delivery systems possessing the ability to follow intranasal (IN) route for brain targeting, which would ultimately ameliorate the effect of AD. This review highlights the various pathological theories for AD along with their controversies. This work intends to provide a thorough, up-to-date, and holistic discussion on various pathways for nose-to-brain delivery and different formulation factors impacting on nasal absorption. The various material properties and their engineered nanocarriers as a smart delivery system, including synergistic effect of therapeutic/biotherapeutic agent in IN delivery as well as in AD therapy have been discussed. This review also emphasizes toxicity, especially neurotoxicity concerns pertaining to drug delivery systems.

Polymeric Immunonanoparticles Mediated Cancer Therapy: Versatile Nanocarriers for Cell-Specific Cargo Delivery.

The major drawback with conventional therapeutic approaches for cancer therapy is decreased efficacy and redundant therapy associated toxicity and side effects causing increased patient discomfort. With the aim of minimizing these limitations, a vast amount of attention has been given to targeted nanocarrier-based drug delivery systems that possess a several-fold advantage over conventional therapy. Increased research in targeted nanoparticulate systems has led to the development of immunonanoparticles with enhanced efficacy and targeting efficiency along with decreased drug-resistant cancer- and dose-related toxicity. These immunonanoparticle- based therapies, which can be extended to immunotherapy, have gained wide attention, but few formulations will be approved by regulatory agencies in the near future. This review details the various immunonanoparticle systems explored in cancer therapy, with particular emphasis on polymeric nanoparticles. This review describes the mechanisms of immunotherapy and the pathways for targeting dendritic cells for immunotherapy. It also focuses on present status of clinical trials of immunonanoparticles and related patents, as well as various FDA-approved monoclonal antibodies (mAbs) for immunotherapy. Toxicity issues related to immunonanoparticles along with regulatory guidelines for these therapeutic nanoparticles are also discussed.

Albumin based versatile multifunctional nanocarriers for cancer therapy: Fabrication, surface modification, multimodal therapeutics and imaging approaches.

Albumin is a versatile protein used as a carrier system for cancer therapeutics. As a carrier it can provide tumor specificity, reduce drug related toxicity, maintain therapeutic concentration of the active moiety like drug, gene, peptide, protein etc. for long period of time and also reduce drug related toxicities. Apart from cancer therapy, it is also utilized in the imaging and multimodal therapy of cancer. This review highlights the important properties, structure and types of albumin based nanocarriers with regards to their use for cancer targeting. It also provides brief discussion on methods of preparation of these nanocarriers and their surface modification. Applications of albumin nanocarriers for cancer therapy, gene delivery, imaging, phototherapy and multimodal therapy have also been discussed. This review also provides brief discussion about albumin based marketed nano formulations and those under clinical trials.