Chitosan: Structural modification, biological activity and application.

Microneedles for painless transdermal immunotherapeutic applications

Chitosan: A review of molecular structure, bioactivities and interactions with the human body and micro-organisms.

Advanced engineered nanoparticulate platforms to address key biological barriers for delivering chemotherapeutic agents to target sites.

Carrier-free nanodrugs with efficient drug delivery and release for cancer therapy: From intrinsic physicochemical properties to external modification.

Microneedle (MN) arrays offer an alternative approach to hypodermic injection via syringe needles. In this work, polyvinylpyrrolidone (PVP)-based fast dissolving MN arrays were developed in which the needle tips were loaded with chitosan nanoparticles (NPs) for coencapsulation of a model antigen, ovalbumin (OVA), and an adjuvant, CpG oligodeoxynucleotides (CpG). After insertion into the skin, these MN arrays fully dissolved within 3 min to release antigen and adjuvant co-loaded NPs rapidly in the epidermal layer. Positively charged chitosan was proven to be an excellent carrier for negatively charged OVA and CpG, which formed nanocomplexes via simple electrostatic interactions and greatly enhanced the uptake efficiency of OVA in DC2.4 dendritic cells. Vaccination studies in mice further demonstrated that chitosan NPs effectively accumulated in peripheral lymph nodes, thus inducing greatly enhanced immune responses compared to those of free OVA. The antibody dose–response curve further demonstrated that MN immunization achieved comparable levels of immune responses as compared to conventional subcutaneous injections in a more convenient and less invasive way. Overall, a PVP-based fast dissolving MN array with chitosan NPs represents a promising and robust platform system for efficient transcutaneous vaccine delivery.

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A fast-dissolving microneedle array loaded with chitosan nanoparticles to evoke systemic immune responses in mice

An all in one nano-system with active-targeting, enzyme-triggered deshielding and positive-charge characteristics was fabricated for chemo/photo-combination therapy to allow efficient tumor targeting, cellular internalization and lysosomal escape The deshielding of NPs was induced by enzyme triggered degradation of the NP shell, and consequently exposure of the positively charged core accelerates escape of NPs from the lysosome to exert anticancer effects with high efficiency

Enzyme-triggered deshielding of nanoparticles and positive-charge mediated lysosomal escape for chemo/photo-combination therapy.

A bilayer microneedle for therapeutic peptide delivery towards the treatment of diabetes in db/db mice

OBJECTIVE To develop poly(d,l-lactide-co-glycolide) (PLGA) microspheres to achieve controlled and sustained release of brexpiprazole in vivo. METHODS Brexpiprazole microspheres were prepared by oil-in-water emulsion-solvent evaporation method and evaluated for morphology, particle size, encapsulation efficiency, drug loading, conformation and compatibility of drug and polymer, in vitro release, and in vivo pharmacokinetics. By establishing the relationship between in vitro and in vivo release, it helps identify the appropriate in vitro release conditions to explore release profiles of brexpiprazole microspheres. RESULTS Porous PLGA microspheres with near spherical morphology were obtained displaying an average diameter of 20.43 ± 0.06 μm, a drug loading capacity of 27.24 ± 0.33% and an encapsulation efficiency of 81.87 ± 1.07%. Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC) analysis showed that some drugs encapsulated in the microspheres remained in the amorphous state and some were in the crystalline state. Different release setups resulted in different release kinetics. The dialysis release setup displayed a cumulative release of about 65% within 60 days, while the sample-and-separate setup showed a cumulative release of about 77% within 35 days. Per pharmacokinetic studies in rats, a burst phase in the plasma concentration-time curve was observed after intramuscular injection in the first 2 h followed by a clear zero-order release phase. Overall, brexpiprazole achieved in vivo sustained release from PLGA microspheres for up to 40 days. CONCLUSION A PLGA microsphere loaded with brexpiprazole was successfully developed and demonstrated potential for extended-release of therapeutics for schizophrenia treatment.

Yingju He

Papers

A fast-dissolving microneedle array loaded with chitosan nanoparticles to evoke systemic immune responses in mice

Enzyme-triggered deshielding of nanoparticles and positive-charge mediated lysosomal escape for chemo/photo-combination therapy.

A bilayer microneedle for therapeutic peptide delivery towards the treatment of diabetes in db/db mice

Engineered PLGA microspheres for extended release of brexpiprazole: in vitro and in vivo studies.