Preparation of Hollow Porous HAP Microspheres as Drug Delivery Vehicles

Hollow HAP microspheres in sub-millimeter size were prepared and investigated as a drug delivery vehicle. The LCB （lithium-calcium borate） glass microspheres, which were made through flame spray process, were chosen as precursor for hollow HAP microspheres. The LCB glass microspheres reacted with phosphate buffer （K2HPO4） solution for 5 days at 37 ℃. During the reaction the Ca-P-OH compound precipitated on the surface of LCB glass microspheres and formed porous shells. Then the microspheres turned to be hollow ones with the same diameter as the glass microspheres after LCB glass run out in the chemical reaction. After heat-treated at 600 ℃ for 4 h, the Ca-P-OH compound became HAP, thus the hollow HAP microspheres were produced. The mechanism of forming hollow HAP microspheres through the chemical reaction between phosphate buffer and LCB glass was confirmed by the XRD analysis. The microstructure characteristics of the hollow, porous microspheres were observed by SEM.

Nanomaterial-based delivery vehicles for therapeutic cancer vaccine development

Nanomaterial-based delivery vehicles such as lipid-based,polymer-based,inorganics-based,and bio-inspired vehicles often carry distinct and attractive advantages in the development of therapeutic cancer vaccines.Based on various delivery vehicles,specifically designed nanomaterials-based vaccines are highly advantageous in boosting therapeutic and prophylactic antitumor immunities.Specifically,therapeutic vaccines featuring unique properties have made major contributions to the enhancement of antigen immunogenicity,encapsulation efficiency,biocompatibility,and stability,as well as promoting antigen cross-presentation and specific CD8^(+)T cell responses.However,for clinical applications,tumor-associated antigen-derived vaccines could be an obstacle,involving immune tolerance and deficiency of tumor specificities,in achieving maximum therapeutic indices.However,when using bioinformatics predictions with emerging innovations of in silico tools,neoantigen-based therapeutic vaccines might become potent personalized vaccines for tumor treatments.In this review,we summarize the development of preclinical therapeutic cancer vaccines and the advancements of nanomaterial-based delivery vehicles for cancer immunotherapies,which provide the basis for a personalized vaccine delivery platform.Moreover,we review the existing challenges and future perspectives of nanomaterial-based personalized vaccines for novel tumor immunotherapies.

Food-derived exosomes as the future of drug delivery

Exosomes are a kind of nanoscale membrane vesicles that can be secreted by many types of cells in both normal and pathological states and play a very important role in intercellular information exchange and transmission by transporting proteins, nucleic acids, lipids, and other biologically active substances to act on the receptor cells. Recent studies have shown that exosomes from some plants, animals, microorganisms, and other food sources can also be extracted like the structure of exosomes secreted by mammalian cells, which are named food-derived exosomes (FDEs) and can be absorbed by intestinal cells and further transported to other organs through blood circulation. With the advantages of high biocompatibility, low immunogenicity, low toxicity, high cargo capacity, and the ability to cross biological barriers, FDEs can be involved in a variety of applications such as immune response, cell migration, and tumor invasion, and have attracted a lot of attention as biotherapeutic agents and drug delivery carriers in the treatment of human diseases. This article reviews the classification, preparation characterization, physiological processes in the human body, biological functions, and application prospects of FDEs. It aims to provide a reference for the research and application of FDEs in disease treatment.

Rational design of oral drugs targeting mucosa delivery with gut organoid platforms

Effective oral drugs and vaccines require high delivery efficiency across the gastrointestinal epithelia and protection of medically effective payloads(i.e.,immunogens)against gastric damage.In this study,hollowed nanocarriers(NCs:silica nanospheres and gold nanocages)with poly-l-lysine(PLL)coating and mammalian orthoreovirus cell attachment proteinσ1 functionalization(NC-PLL-σ1)were explored as functional oral drug delivery vehicles(ODDVs).The transport of these ODDVs to mucosal lymphoid tissues could be facilitated by microfold cells(M-cells)mediated transcytosis(viaσ1-α2–3-linked sialic acids adherence)across gastrointestinal epithelia.PLL coating provided protection and slow-release of rhodamine 6 G(R6G),a model payload.The transport effectiveness of these ODDVs was tested on intestinal organoid monolayers in vitro.When compared with other experimental groups,the fully functionalized ODDV system(with PLL-σ1)demonstrated two significant advantages:a significantly higher transport efficiency(198%over blank control at 48 h);and protection of payloads which led to both better transport efficiency and extended-release of payloads(61%over uncoated carriers at 48 h).In addition,it was shown that the M cell presence in intestinal organoid monolayers(modulated by Rank L stimulation)was a determining factor on the transport efficiency of the ODDVs:more M-cells(induced by higher Rank L)in the organoid monolayers led to higher transport efficiency for ODDV-delivered model payload(R6G).The fully functionalized ODDVs showed great potential as effective oral delivery vehicles for drugs and vaccines.

Short review on liquid membrane technology and their applications in biochemical engineering

As a branch of membrane separation technology,liquid membrane has attracted great attention and expanded investigations in biological chemical engineering,with life and health concern in ecosystems.Composed of membrane solvent and mobile carrier,liquid membrane was acquired of function,performing the facilitated mass transfer across the diffusive solvent,so as for the separation and delivery achievement with efficacy.In this review,two types of liquid membrane are mainly focused,respectively on supported liquid membrane(SLM)of membrane solvent supporter in necessity,and on emulsion liquid membrane(ELM)of the required interfacial stabilizers and homogenization.Accordingly,the transfer mechanism,compositions,structure and features of SLM and ELM are introduced respectively.Moreover,the current investigations of liquid membrane have been discussed,focusing on the improvements of efficacy and stability in separation&detection,encapsulation and delivery,so as to scale up the favorable and efficient application with bio-life concern.Prospectively,this review could provide comprehensive insight into the bio-applications of liquid membrane,and guidelines for the further investigations on the efficacy and long-term applicable stability,in order to realize the industrialization.

Integrated multi-item packaging and vehicle routing with split delivery problem for fresh agri-product emergency supply at large-scale epidemic disease context

Fresh agri-product emergency supply is crucial to secure the basic livelihood of residents at large-scale epidemic disease context. Considering the massive demand and limited transportation resources, this study integrates multi-item packaging and vehicle routing with split delivery to improve the emergency supply capacity. Firstly, three specific objectives of fresh agri-product emergency supply at large-scale epidemic disease context are formulated, i.e., average response time, infectious risk possibility and transportation resource utilization. Then, a multi-item packaging strategy is proposed to consolidate different categories of fresh agri-products according to the food cold chain temperatures.An optimization model integrating multi-item packaging and vehicle routing with split delivery is developed to jointly decide the optimal packaging scheduling, vehicle assignment and delivery routing. Next, an improved genetic algorithm based on solution features (IGA-SF) is designed to solve the integrated model with multiple decision variables. Finally,a case on fresh agri-product emergency supply of Huangpi District, Wuhan in the context of the Corona Virus Disease 2019(COVID-19) is carried out to illustrate the efficiency and feasibility of the proposed model. The numerical results of medium-to-largescale cases demonstrate that the proposed IGA-SF could save 23.91% CPU time and 37.80% iteration number on average than genetic algorithm. This study could satisfy different emergency scenario requirements flexibly, and provide scientific decision support for provincial and national governments on fresh agri-product emergency supply.

A two-stage heuristic method for vehicle routing problem with split deliveries and pickups

The vehicle routing problem(VRP) is a well-known combinatorial optimization issue in transportation and logistics network systems. There exist several limitations associated with the traditional VRP. Releasing the restricted conditions of traditional VRP has become a research focus in the past few decades. The vehicle routing problem with split deliveries and pickups(VRPSPDP) is particularly proposed to release the constraints on the visiting times per customer and vehicle capacity, that is, to allow the deliveries and pickups for each customer to be simultaneously split more than once. Few studies have focused on the VRPSPDP problem. In this paper we propose a two-stage heuristic method integrating the initial heuristic algorithm and hybrid heuristic algorithm to study the VRPSPDP problem. To validate the proposed algorithm, Solomon benchmark datasets and extended Solomon benchmark datasets were modified to compare with three other popular algorithms. A total of 18 datasets were used to evaluate the effectiveness of the proposed method. The computational results indicated that the proposed algorithm is superior to these three algorithms for VRPSPDP in terms of total travel cost and average loading rate.