Preparation and characterization of bupivacaine multivesicular liposome: A QbD study about the effects of formulation and process on critical quality attributes.

This study extends QbD principles to liposomal products containing a hydrophilic active pharmaceutical ingredient (API). The feasibility and advantages of the QbD concept for multivesicular liposome-based systems were demonstrated. We selected the local anesthetic drug bupivacaine as a model compound.

Micelles with ultralow critical micelle concentration as carriers for drug delivery.

Conventional micellar carriers disassemble into free surfactants when diluted at concentrations below the critical micelle concentration (CMC). This limits the bioavailability in vivo of injected hydrophobic drugs encapsulated in micellar systems. Here, we show that a micelle comprising a superhydrophilic zwitterionic polymer domain and a superhydrophobic lipid domain has an undetectable CMC below 10 mM-a value that is orders of magnitude lower than the CMCs (>10 mM) of typical micellar systems.

Current Strategy for Cisplatin Delivery.

Cisplatin is one of the leading chemotherapy drugs currently used in clinical settings. However, its serious side effects and its resistance developed by tumor cells hinder its usage. To decrease its side effects and maintain anti-cancer efficiency, various cisplatin based formulations were developed.

Programmed co-delivery of paclitaxel and doxorubicin boosted by camouflaging with erythrocyte membrane.

Combination chemotherapy has been proven promising for cancer treatment, but unsatisfactory therapeutic data and increased side effects slow down the development in the clinic. In this study, we develop an effective approach to co-encapsulate a hydrophilic-hydrophobic chemotherapeutic drug pair (paclitaxel and doxorubicin) into magnetic O-carboxymethyl-chitosan nanoparticles. To endow them with the ability of programmed delivery, these carriers are further camouflaged with an Arg-Gly-Asp anchored erythrocyte membrane.

Ultrastable core-shell structured nanoparticles directly made from zwitterionic polymers.

A novel strategy was achieved to make ultra-stable core-shell nanoparticles directly from nonfouling zwitterionic polymers through a one-step microwave method. The resulting nanoparticles showed superior colloid stability in bio-relevant media and even under freeze-drying conditions.

Novel vaccine delivery system induces robust humoral and cellular immune responses based on multiple mechanisms.

Aiming to enhance the immunogenicity of H5N1 split vaccine, the development of a novel antigen delivery system based on quaternized chitosan hydrogel microparticles (Gel MPs) with multiple mechanisms of immunity enhancement is attempted. Gel MPs based on ionic cross-linking are prepared in a simple and mild way. Gel MPs are superior as a vaccine delivery system due to their ability to: 1) enhance cellular uptake and endosomal escape of antigens in dendritic cells (DCs); 2) significantly activate DCs; 3) form an antigen depot and recruit immunity cells to improve antigen capture.

Nanoparticles-based multi-adjuvant whole cell tumor vaccine for cancer immunotherapy.

Whole cell tumor vaccine (WCTV), as a potential treatment modality, elicits limited immune responses because of the poor immunogenicity. To address this issue, researchers have attempted to transduce a cytokine adjuvant into tumor cells, but these single-adjuvant WCTVs curtail the high expectations. In present study, we constructed a multi-adjuvant WCTV based on the nanoparticles modified with cell penetrating peptide, which could facilitate the transportation of granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin 2 (IL-2) into tumor cells.

Molecular structure matters: PEG-b-PLA nanoparticles with hydrophilicity and deformability demonstrate their advantages for high-performance delivery of anti-cancer drugs.

Various carriers are being advanced for anti-cancer therapy, which can protect drugs and ferry them to the target site. However, little understanding exists regarding the effect of molecular structure on anti-cancer drug delivery efficiency. To fill this knowledge gap, we take poly(lactic acid) (PLA), poly(lactide-co-glycolide) (PLGA), and poly-ethylene glycol-co-poly-lactide (PEG-b-PLA) polymers as prototype materials and comparatively explore the inherent relationship between the molecular structure and the delivery ability.

Inducible graphene oxide probe for high-specific tumor diagnosis.

A revolutionary probe was constructed by conjugating Cy5 on a graphene oxide sheet. The fluorescence was quenched owing to its proximity to graphene oxide in normal circumstances, but lit on arriving at the tumor site. Both in vitro and in vivo studies demonstrated that the probe exhibits great potential for tumor diagnosis.

Codelivery of mTERT siRNA and paclitaxel by chitosan-based nanoparticles promoted synergistic tumor suppression.

Clinical applications of siRNA are being hindered by poor intracellular uptake and enzymatic degradation. To address these problems, we devised an oral delivery system for telomerase reverse transcriptase siRNA using N-((2-hydroxy-3-trimethylammonium) propyl) chitosan chloride (HTCC) nanoparticles (HNP). Both the porous structure and the positive charge of HNP facilitated siRNA encapsulation.

The role of the lateral dimension of graphene oxide in the regulation of cellular responses.

The nanomaterial graphene oxide (GO) has attracted explosive interests in various areas. However, its performance in biological environments is still largely unknown, particularly with regard to cellular response to GO. Here we separated the GO sheets in different size and systematically investigated size effect of the GO in response to different types of cells.

The orchestration of cellular and humoral responses is facilitated by divergent intracellular antigen trafficking in nanoparticle-based therapeutic vaccine.

Therapeutic vaccination for the treatment of chronic hepatitis B is promising but has so far shown limited clinical efficacy. Herein, we employ polylactide nanoparticles (NPs) as the vaccine adjuvant and systematically explore their effect on activation of specific immunity and the underlying theoretical mechanisms. In vitro studies show that hepatitis B surface antigen (HBsAg) accumulates in antigen-presenting cells (APCs) to a larger content (270%) with the assistant of NP in comparison with the pure-antigen group.

Surface charge affects cellular uptake and intracellular trafficking of chitosan-based nanoparticles.

Chitosan-based nanoparticles (NPs) are widely used in drug delivery, device-based therapy, tissue engineering, and medical imaging. In this aspect, a clear understanding of how physicochemical properties of these NPs affect the cytological response is in high demand. The objective of this study is to evaluate the effect of surface charge on cellular uptake profiles (rate and amount) and intracellular trafficking.

Particle size affects the cellular response in macrophages.

A deeper understanding of how the physical properties of particles regulate specific biological responses is becoming a crucial requirement for their successful biomedical application. To provide insights on their design and application, J774A.1 cells are exposed to particles with different diameters (430 nm, 1.

Galactosylated nanocrystallites of insoluble anticancer drug for liver-targeting therapy: an in vitro evaluation.

Aim: Low solubility in water has become an intrinsic property of many anticancer drugs, which poses a hurdle in the translation from the bench to the clinic. In this study, we developed a facile method to prepare 10-hydroxycamptothecin (HCPT) nanocrystallites and testified their feasibility for liver-targeting therapy.

Materials & Methods: HCPT nanocrystallites were prepared under the soft template effect of galactosylated chitosan.