Due to its safety, convenience, low cost and good compliance, oral administration attracts lots of attention. However, the efficacy of many oral drugs is limited to their unsatisfactory bioavailability in the gastrointestinal tract. One of the critical and most overlooked factors is the symbiotic gut microbiota that can modulate the bioavailability of oral drugs by participating in the biotransformation of oral drugs, influencing the drug transport process and altering some gastrointestinal properties. In this review, we summarized the existing research investigating the possible relationship between the gut microbiota and the bioavailability of oral drugs, which may provide great ideas and useful instructions for the design of novel drug delivery systems or the achievement of personalized medicine.

The efficacy of chemotherapeutic drug in cancer treatment is often hampered by drug resistance of tumor cells, which is usually caused by abnormal gene expression. RNA interference mediated by siRNA and miRNA can selectively knock down the carcinogenic genes by targeting specific mRNAs. Therefore, combining chemotherapeutic drugs with gene agents could be a promising strategy for cancer therapy. Due to poor stability and solubility associated with gene agents and drugs, suitable protective carriers are needed and have been widely researched for the co-delivery. In this review, we summarize the most commonly used nanocarriers for co-delivery of chemotherapeutic drugs and gene agents, as well as the advances in co-delivery systems.

In last few years, therapeutic peptides/proteins are rapidly growing in drug market considering their higher efficiency and lower toxicity than chemical drugs. However, the administration of therapeutic peptides/proteins is mainly limited in parenteral approach. Oral therapy which was hampered by harsh gastrointestinal environment and poorly penetrating epithelial barriers often results in low bioavailability (less than 1%-2%). Therefore, delivery systems that are rationally designed to overcome these challenges in gastrointestinal tract and ameliorate the oral bioavailability of therapeutic peptides/proteins are seriously promising. In this review, we summarized various multifunctional delivery systems, including lipid-based particles, polysaccharide-based particles, inorganic particles, and synthetic multifunctional particles that achieved effective oral delivery of therapeutic peptides/proteins.

Modulating the inflammatory microenvironment can inhibit the process of inflammatory diseases (IDs). A tri‐cross‐linked inflammatory microenvironment‐responsive hydrogel with ideal mechanical properties achieves triggerable and sustained drug delivery and regulates the inflammatory microenvironment. Here, this study develops an inflammatory microenvironment‐responsive hydrogel (OD‐PP@SeNPs) composed of phenylboronic acid grafted polylysine (PP), oxidized dextran (OD), and selenium nanoparticles (SeNPs). The introduction of SeNPs as initiators and nano‐fillers into the hydrogel results in extra cross‐linking of the polymer network through hydrogen bonding. Based on Schiff base bonds, Phenylboronate ester bonds, and hydrogen bonds, a reactive oxygen species (ROS)/pH dual responsive hydrogel with a triple‐network is achieved. The hydrogel has injectable, self‐healing, adhesion, outstanding flexibility, suitable swelling capacity, optimal biodegradability, excellent stimuli‐responsive active substance release performance, and prominent biocompatibility. Most importantly, the hydrogel with ROS scavenging and pH‐regulating ability protects cells from oxidative stress and induces macrophages into M2 polarization to reduce inflammatory cytokines through PI3K/AKT/NF‐κB and MAPK pathways, exerting anti‐inflammatory effects and reshaping the inflammatory microenvironment, thereby effectively treating typical IDs, including S. aureus infected wound and rheumatoid arthritis in rats. In conclusion, this dynamically responsive injectable hydrogel with a triple‐network structure provides an effective strategy to treat IDs, holding great promise in clinical application.

Background: The co-delivery of chemotherapeutic agents and small interfering RNA (siRNA) within one cargo can enhance the anticancer outcomes through its synergistic therapeutic effects. Materials and methods: We prepared smart polymeric nanoparticles (NPs) with pH-responsive and poly(ethylene glycol) (PEG)-detachable properties to systemically co-deliver paclitaxel (PTX) and siRNA against survivin gene for lung cancer therapy. The cationic polyethyleneimine-block-polylactic acid (PEI-PLA) was first synthesized and characterized, with good biocompatibility. PTX was encapsulated into the hydrophobic core of the PEI-PLA polymers by dialysis, and then the survivin siRNA was loaded onto the PTX-loaded NPs (PEI-PLA/PTX) through electrostatic interaction between siRNA and PEI block. Finally, the negatively charged poly(ethylene glycol)-block-poly(l-aspartic acid sodium salt) (PEG-PAsp) was coated onto the surface of NPs by electrostatic interaction to form final smart polymeric NPs with mean particle size of 82.4 nm and zeta potential of 4.1 mV. After uptake of NPs by tumor cells, the PEG-PAsp segments became electrically neutral owing to the lower endosome pH and consequently detached from the smart NPs. This process allowed endosomal escape of the NPs through the proton-sponge effect of the exposed PEI moiety. Results: The resulting NPs achieved drug loading of 6.04 wt% and exhibited good dispersibility within 24 h in 10% fetal bovine serum (FBS). At pH 5.5, the NPs presented better drug release and cellular uptake than at pH 7.4. The NPs with survivin siRNA effectively knocked down the expression of survivin mRNA and protein owing to enhanced cell uptake of NPs. Cell counting kit-8 (CCK-8) assay showed that the NPs presented low systemic toxicity and improved antiproliferation effect of PTX on A549 cells. Moreover, in vivo studies demonstrated that accumulated NPs in the tumor site were capable of inhibiting the tumor growth and extending the survival rate of the mice by silencing the survivin gene and delivering PTX into tumor cells simultaneously. Conclusion: These results indicate that the prepared nano-vectors could be a promising co-delivery system for novel chemo/gene combination therapy.