Preparation of 20 (S)-protopanaxadiol PLGA Nanoparticles

[Objectives]To prepare 20(S)-protopanaxadiol PLGA nanoparticles(20(S)-PPD-PLGA-NPs).[Methods]20(S)-PPD-PLGA-NPs were prepared by emulsion solvent evaporation method,and the optimal formulation was screened by Box-Behnken experiment with particle size and drug loading as the indicators through single factor experiment,and the drug release in vitro was carried out.[Results]The average diameter of the nanoparticles was(119.60±2.29)nm and the polydispersity index was(0.12±0.02),the size was uniform.The encapsulation efficiency and drug loading of protopanaxadiol were(87.99±1.29)%and(14.86±0.25)%,respectively.[Conclusions]The 20(S)-PPD-PLGA-NPs were successfully prepared by emulsion solvent evaporation method,and the 20(S)-PPD-PLGA-NPs had good stability,to lay a foundation for the study of 20(S)-PPD-PLGA-NPs in vitro and in vivo.

TPGS/hyaluronic acid dual-functionalized PLGA nanoparticles delivered through dissolving microneedles for markedly improved chemo-photothermal combined therapy of superficial tumor

Nanoparticles(NPs)have shown potential in cancer therapy,while a single administration conferring a satisfactory outcome is still unavailable.To address this issue,the dissolving microneedles(DMNs)were developed to locally deliver functionalized NPs with combined chemotherapy and photothermal therapy(PTT).α-Tocopheryl polyethylene glycol succinate(TPGS)/hyaluronic acid(HA)dualfunctionalized PLGA NPs(HD10 NPs)were fabricated to co-load paclitaxel and indocyanine green.HD10 NPs significantly enhanced the cytotoxicity of low-dose paclitaxel because of active and mitochondrial targeting by HA and TPGS,respectively.PTT could further sensitize tumor cells toward chemotherapy by promoting apoptosis into the advanced period,highly activating caspase 3 enzyme,and significantly reducing the expression of survivin and MMP-9 proteins.Further,the anti-tumor effects of HD10 NPs delivered through different administration routes were conducted on the 4 T1 tumorbearing mice.After a single administration,HD10 NPs delivered with DMNs showed the best antitumor effect when giving chemotherapy alone.As expected,the anti-tumor effect was profoundly enhanced after combined therapy,and complete tumor ablation was achieved in the mice treated with DMNs and intra-tumor injection.Moreover,DMNs showed better safety due to moderate hyperthermia.Therefore,the DMNs along with combined chemo-photothermal therapy provide a viable treatment option for superficial tumors.

Uptake and traffcking of different sized PLGA nanoparticles by dendritic cells in imiquimod-induced psoriasis-like mice model

Psoriasis is an autoimmune infammatory disease,where dendritic cells(DCs)play an important role in its pathogenesis.In our previous work,we have demonstrated that topical delivery of curcumin-loaded poly(lactic-co-glycolic acid)(PLGA)nanoparticles(NPs)could treat Imiquimod(IMQ)-induced psoriasis-like mice.The objective of this study is to further elucidate biofate of PLGA NPs after intradermal delivery including DCs uptake,and their further traffcking in psoriasis-like mice model by using fuorescence probes.Two-sized DiO/DiI-loaded PLGA NPs of 50±4.9 nm(S-NPs)and 226±7.8 nm(L-NPs)were fabricated,respectively.In vitro cellular uptake results showed that NPs could be internalized into DCs with intact form,and DCs preferred to uptake larger NPs.Consistently,in vivo study showed that L-NPs were more captured by DCs and NPs were frstly transported to skindraining lymph nodes(SDLN),then to spleens after 8 h injection,whereas more S-NPs were transported into SDLN and spleens.Moreover,FRET imaging showed more structurally intact L-NPs distributed in skins and lymph nodes.In conclusion,particle size can affect the uptake and traffcking of NPs by DCs in skin and lymphoid system,which needs to be considered in NPs tailing to treat infammatory skin disease like psoriasis.

PLGA nanoparticle encapsulated paclitaxol for sustained release and its anticancer effect for HeLa cells in vitro

Poly (D,L-lactide-co-glycolide) (PLGA) is a biodegradable and biocompatible polymer material for drug deliver system. The aim of this study is to synthesize drug-loaded

Oral nano-formulation improves pancreatic islets dysfunction via lymphatic transport for antidiabetic treatment

Type 2 diabetes mellitus(T2DM)therapy is facing the challenges of long-term medication and gradual destruction of pancreatic isletβ-cells.Therefore,it is timely to develop oral prolonged action formulations to improve compliance,while restoringβ-cells survival and function.Herein,we designed a simple nanoparticle with enhanced oral absorption and pancreas accumulation property,which combined apical sodiumdependent bile acid transporter-mediated intestinal uptake and lymphatic transportation.In this system,taurocholic acid(TCA)modified poly(lactic-co-glycolic acid)(PLGA)was employed to achieve pancreas location,hydroxychloroquine(HCQ)was loaded to execute therapeutic efficacy,and 1,2-dilauroyl-sn-glycero-3-phosphocholine(DLPC)was introduced as stabilizer together with synergist(PLGA-TCA/DLPC/HCQ).In vitro and in vivo results have proven that PLGA-TCA/DLPC/HCQ reversed the pancreatic islets damage and dysfunction,thus impeding hyperglycemia progression and restoring systemic glucose homeostasis via only once administration every day.In terms of mechanism PLGA-TCA/DLPC/HCQ ameliorated oxidative stress,remodeled the inflammatory pancreas microenvironment,and activated PI3K/AKT signaling pathway without obvious toxicity.This strategy not only provides an oral delivery platform for increasing absorption and pancreas targetability but also opens a new avenue for thorough T2DM treatment.

Sustained release of methyl viologen from a novel nanoparticle delivery system with double shells of silica and PLGA

The use of nanotechnology in drug delivery is a rapidly expanding field. Biodegradable or nontoxic nanomaterials have the most promising application potentials in nanomedicine.