Development of nanomedicines for the treatment of Alzheimer's disease: Raison d'être, strategies, challenges and regulatory aspects.

Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by progressive loss of memory. Presently, AD is challenging to treat with current drug therapy as their delivery to the brain is restricted by the presence of the blood-brain barrier. Nanomedicines, due to their size, high surface volume ratio, and ease of tailoring drug release characteristics, showed their potential to treat AD. The nanotechnology-based formulations for brain targeting are expected to enter the market in the near future. So, regulatory frameworks are required to ensure the quality, safety, and effectiveness of the nanomedicines to treat AD. In this review, we discuss different strategies, in-vitro blood-brain permeation models, in-vivo permeation assessment, and regulatory aspects for the development of nanomedicine to treat AD.

Bioinspired theranostic quantum dots: Paving the road to a new paradigm for cancer diagnosis and therapeutics.

Despite extensive research, a complete cure remains lacking for most types of cancer. Nanotechnology-based carriers, such as liposomes, nanoparticles (NPs), dendrimers, nanoemulsions, and other nanocarriers, can target cancer cells, but their in vivo fate is unpredictable. Bioinspired quantum dots (BQDs) offer enhanced aqueous solubility, exceptionally low toxicity, biocompatibility, easy biofunctionalization, and selective cancer targeting. Due to their photoluminescence, high longitudinal relaxation value, photothermal effect upon laser irradiation, generation of singlet oxygen, and production of H2S for gas therapy, BQDs are excellent cancer theranostic agents. In this review, we highlight the theranostic application of, and existing challenges relating to BQDs.

Recent advances on biodegradable polymeric carrier-based mucosal immunization: an overview.

Mucosal administration of vaccine is most prevalent way to induce desired immunity against various types of antigen and microbial in central and in addition, the peripheral blood in most external mucosal surface. Mucosal delivery of vaccine provides both humoral and cellular responses against mucosal infection. Mucosa, which are exposed to heavy loads of commensal and pathogenic microorganism, are one of the main region where infections are built up, also, thus have frontline status in immunity, making mucosa perfect site for vaccines application. The nasal route is favoured over parenteral route due to ease of administration, protection of antigen from degradation and induces sIgA which is not produced by systemic immunity. Natural and synthetic polymers are utilized to get nanoparticles carrier systems for development of nasal mucosal antibodies. The present review summarized the recent development in the field of vaccine delivery by means of mucoadhesive polymeric carriers. This review also describes the recent patent conceded for mucosal immunization utilizing these polymeric carriers.

Preparation and characterization of HA-PEG-PCL intelligent core-corona nanoparticles for delivery of doxorubicin.

The objective of the present study was to synthesize core-corona nanoparticles of doxorubicin (DOX) using hyaluronic acid-polyethyleneglycol-polycaprolactone (HA-PEG-PCL) copolymer for tumor targeting. Targeting efficiency of HA-PEG-PCL nanoparticles was compared with non-HA-containing nanoparticles (methoxy poly ethylene glycol (MPEG)-PCL). The copolymers were chemically synthesized and characterized by IR and NMR spectroscopies. The nanoparticles were characterized for shape and morphology by transmission electron microscopy, particle size, percentage of drug entrapment, and in vitro drug release profile. Differential scanning calorimetry and X-ray diffraction studies were also performed to appraise the crystalline or amorphous nature of DOX inside the polymer matrix. Formulations were prepared using different DOX:polymer ratios (1:1-1:3 w/w) and the optimum formulation with the drug:polymer ratio of 1:1 showed the mean particle size of 95 +/- 5 nm and entrapment efficiency of 95.56% in the case of HA-PEG-PCL nanoparticles, while the values were 115 nm and 95.50%, respectively, in the case of MPEG-PCL nanoparticles. The HA-PEG-PCL nanoparticles could release DOX for up to 17 days, whereas the MPEG-PCL nanoparticles could release it for up to 14 days. The hemolytic toxicity and hematological studies confirmed that both DOX-loaded HA-PEG-PCL and MPEG-PCL nanoparticles were safe and suitable for sustained and targeted drug delivery. The tissue distribution study and tumor growth inhibition were performed after intravenous injection of nanoparticles in Ehrlich ascites tumor (EAT)-bearing mice. The nanoparticles of HA-PEG-PCL copolymer accomplishes efficient delivery of DOX in EAT tumor when compared with the MPEG-PCL nanoparticles by the process of receptor-mediated endocytosis, as well as enhanced permeability and retention effect.

Development and characterization of hyaluronic acid-anchored PLGA nanoparticulate carriers of doxorubicin.

A novel hyaluronic acid-poly(ethylene glycol)-poly(lactide-co-glycolide) (HA-PEG-PLGA) copolymer was synthesized and characterized by infrared and nuclear magnetic resonance spectroscopy. The nanoparticles of doxorubicin (DOX)-loaded HA-PEG-PLGA were prepared and compared with monomethoxy(polyethylene glycol) (MPEG)-PLGA nanoparticles. Nanoparticles were prepared using drug-to-polymer ratios of 1:1 to 1:3. Drug-to-polymer ratio of 1:1 is considered the optimum formulation on the basis of low particle size and high entrapment efficiency. The optimized nanoparticles were characterized for morphology, particle size measurements, differential scanning calorimetry, x-ray diffractometer measurement, drug content, hemolytic toxicity, subacute toxicity, and in vitro DOX release. The in vitro DOX release study was performed at pH 7.4 using a dialysis membrane. HA-PEG-PLGA nanoparticles were able to sustain the release for up to 15 days. The tissue distribution studies were performed with DOX-loaded HA-PEG-PLGA and MPEG-PLGA nanoparticles after intravenous (IV) injection in Ehrlich ascites tumor-bearing mice. The tissue distribution studies showed a higher concentration of DOX in the tumor as compared with MPEG-PLGA nanoparticles. The in vivo tumor inhibition study was also performed after IV injection of DOX-loaded HA-PEG-PLGA nanoparticles up to 15 days. DOX-loaded HA-PEG-PLGA nanoparticles were able to deliver a higher amount of DOX as compared with MPEG-PLGA nanoparticles. The DOX-loaded HA-PEG-PLGA nanoparticles reduced tumor volume significantly as compared with MPEG-PLGA nanoparticles.