At present, nonviral gene vectors develop rapidly, especially cationic polymers. A series of bioreducible poly(amide amine) (PAA) polymers containing guanidino groups have been synthesized by our research team. These novel polymer vectors demonstrated significantly higher transfection efficiency and lower cytotoxicity than polyethylenimine (PEI)-25kDa.
View Article and Find Full Text PDFAs a cationic non-viral gene delivery vector, poly(agmatine/ N, N'-cystamine-bis-acrylamide) (AGM-CBA) showed significantly higher plasmid DNA (pDNA) transfection ability than polyethylenimine (PEI) in NIH/3T3 cells. The transfection expression of AGM-CBA/pDNA polyplexes was found to have a non-linear relationship with AGM-CBA/pDNA weight ratios. To further investigate the mechanism involved in the transfection process of poly(AGM-CBA), we used pGL3-control luciferase reporter gene (pLUC) as a reporter pDNA in this study.
View Article and Find Full Text PDFExosomes have been extensively explored as delivery vehicles due to low immunogenicity, efficient cargo delivery, and possibly intrinsic homing capacity. However, therapeutic application of exosomes is hampered by structural complexity and lack of efficient techniques for isolation and drug loading. Liposomes represent one of the most successful therapeutic nanocarriers, but are frequently criticized by short blood circulation and inefficient intracellular drug delivery.
View Article and Find Full Text PDFThis paper aimed to develop a novel lipid microsphere delivering cabazitaxel (CTX) using phosphatidylcholine combined with DSPE-PEG2000 as emulsifier, and evaluate its stability, pharmacokinetics, antitumor efficacy, and toxicity. The pegylated cabazitaxel-loaded lipid microspheres (CTX-PLMs) were prepared by high-pressure homogenization methods; the biological samples were analyzed by the UPLC-MS/MS method. CTX-PLMs had a drug concentration of 1.
View Article and Find Full Text PDFGuanidinylated bioresponsive poly(amido amine)s polymers, CAR-CBA and CHL-CBA, were synthesized by Michael-type addition reaction between guanidine hydrochloride (CAR) or chlorhexidine (CHL) and N,N'-cystaminebisacrylamide (CBA). Previous studies have shown that both polymers had high transfection efficiencies as gene delivery carriers. In this study, we investigated the nucleolus localization abilities and cellular internalization pathways of these two polymers in gene delivery.
View Article and Find Full Text PDFExtracellular vesicles (EVs) are membrane enclosed vesicles that are shed by almost all cell types, and play a fundamental role in cell-to-cell communication. The discovery that EVs are capable of functionally transporting nucleic acid- and protein-based cargoes between cells, rapidly promotes the idea of employing them as drug delivery systems. These endogenous vesicles indeed hold tremendous promise for therapeutic delivery.
View Article and Find Full Text PDFUnlabelled: Cell-free (CF) protein synthesis has emerged as a powerful technique platform for efficient protein production in vitro. Liposomes have been widely studied as therapeutic carriers due to their biocompatibility, biodegradability, low toxicity, flexible surface manipulation, easy preparation, and higher cargo encapsulation capability. However, rapid immune clearance, insufficient targeting capacity, and poor cytoplasmic delivery efficiency substantially restrict their clinical application.
View Article and Find Full Text PDFThe aim of this work was to prepare ascending release compression-coated (CC) tablets with paliperidone (PAL) using a simple manufacturing technique and short manufacturing process. The release behavior and mechanisms of the final tablets was investigated and evaluated. The PAL CC tablets were comprised of a core layer of high viscosity hydroxypropyl cellulose (HPC-H) and a coating layer of high viscosity hydroxypropyl methylcellulose (HPMC-K100M).
View Article and Find Full Text PDFRNA interfering (RNAi), mediated by small interfering RNAs and microRNAs, is currently one of the most promising tools of gene therapy. Small RNAs are capable of inducing specific post-transcriptional gene silencing, providing a potentially effective platform for the treatment of a wide array of diseases. However, similar to other nucleic acid-based drugs, the major hurdle of RNAi therapy is lack of efficient and non-immunogenic delivery vehicles.
View Article and Find Full Text PDFPreviously, we synthesized a non-viral vector containing disulfide bond by polymerization of agamatine (AGM) and N,N'-cystaminebisacrylamide (CBA). In this study, we investigated the transfection efficiency of disulfide bond (SS) containing AGM-CBA polymer in gene delivery into NIH/3T3 cells, and examined the factors affecting its transfection efficiency by comparing with polyethylenimine (PEI). In addition, experiments were carried out to determine the mechanisms of cell entry pathways and intracellular behavior of AGM-CBA/pDNA polyplexes.
View Article and Find Full Text PDFUnlabelled: Polymers are widely studied as non-viral gene vectors because of their strong DNA binding ability, capacity to carry large payload, flexibility of chemical modifications, low immunogenicity, and facile processes for manufacturing. However, high cytotoxicity and low transfection efficiency substantially restrict their application in clinical trials. Incorporating functional peptides is a promising approach to address these issues.
View Article and Find Full Text PDFExtracellular vesicles (EVs) are intrinsic mediators of intercellular communication in our body, allowing functional transfer of biomolecules (lipids, proteins, and nucleic acid) between diverse locations. Such an instrumental role evokes a surge of interest within the drug delivery community in tailoring EVs for therapeutic delivery. These vesicles represent a novel generation of drug delivery systems, providing high delivery efficiency, intrinsic targeting properties, and low immunogenicity.
View Article and Find Full Text PDFAspirin is apt to hydrolyze. In order to improve its stability, a new method has been developed involving the application of hot-melt sub- and outercoating combined with enteric aqueous coating. The main aim was to investigate the influence of these factors on the stability of ASA and understand how they work.
View Article and Find Full Text PDFIn order to achieve high drug loading and high entrapment efficiency, a doxorubicin-cholesteryl hemisuccinate ion-pair complex (DCHIP) was formed, and the ion-pair complex liposomes (DCHIP-Lip) were prepared based on conventional thin-film dispersion method. Firstly, DCHIP was fabricated and confirmed with FTIR, H-NMR, DSC, and XRD techniques. Afterwards, DCHIP-Lip were prepared and evaluated in terms of particle size, zeta potential, entrapment efficiency, and drug loading content.
View Article and Find Full Text PDFTwo different disulfide (SS)-containing poly(amidoamine) (PAA) polymers were constructed using guanidino (Gua)-containing monomers (ie, arginine [Arg] and agmatine [Agm]) and ,'-cystamine bisacrylamide (CBA) by Michael-addition polymerization. In order to characterize these two Gua-SS-PAA polymers and investigate their potentials as short hairpin RNA (shRNA)-delivery carriers, pSilencer 4.1-CMV shRNA was chosen as a model plasmid DNA to form complexes with these two polymers.
View Article and Find Full Text PDFPolymers of guanidinylated disulfide containing poly(amido amine)s (Gua-SS-PAAs), have shown high transfection efficiency and low cytotoxicity. Previously, we synthesized two Gua-SS-PAA polymers, using guanidino containing monomers (i.e.
View Article and Find Full Text PDFPoly(amido amine)s' (PAAs) versatility are nearly unique among stepwise polymers. Different functional groups can be easily introduced into these polymers to add functionality such as cell internalization, charge-shift, bioreducibility, "stealth" properties, and targeting moieties, while maintaining the bulk structural integrity of these polymers. The poly(amido amine)s are used as a unique research platform to elucidate their complex structure-function relationship.
View Article and Find Full Text PDFGuanidinylated poly(amido amine)s with multiple disulfide linkages (Gua-SS-PAAs) were designed and constructed as nonviral gene carriers. The main chains of these novel carriers were synthesized based on monomers containing guanidino groups (guanidine hydrochloride and chlorhexidine), which could avoid complicated side-chain-modification reactions while introducing the guanidino groups. The synthesized Gua-SS-PAAs polymers were characterized by (1)H nuclear magnetic resonance, molecular weight, and polydispersity.
View Article and Find Full Text PDFColloids Surf B Biointerfaces
November 2016
Pluronic F127 and PEG as a multi-gel-core were used to prepare Exenatide-loaded microspheres and store the drug within the microspheres. Also, the sol-gel transition and novel functions of the Pluronic F127-PEG gel core were investigated.Microspheres with a multi-gel-core (GCMs) and without a multi-gel-core (Ms) were compared in terms of the rate of PLGA degradation, therelease kinetics in vitro and the efficacy in KKAy mice.
View Article and Find Full Text PDFObjective: The aim of this study was to improve the drug loading (DL) and stability of clarithromycin (CLA)-loaded liposomes, and reduce the irritation caused by intravenous administration of CLA.
Methods: A CLA-cholesteryl hemisuccinate (CHEMS) ion pair (CIP) was prepared by the solvent evaporation method and confirmed by fourier transform infrared spectroscopy, (1)H-nuclear magnetic resonance, differential scanning calorimetry and X-ray powder diffraction. Subsequently, CIP liposomes (CIP-Lip) were prepared by the thin-film dispersion method and evaluated in terms of their size, zeta-potential, in vitro release, stability, in vitro antimicrobial activity and irritation.
Triblock copolymers, Monomethoxy (Polyethylene glycol)-b-P(D,L-lactic-co-glycolic acid)-b-P(L-glutamic acid) (mPEG-PLGA-PGlu) with different molecular weights, were synthesized and mPEG(5k)-PLGA(20.5k)-PGlu(7.9k) were self-assembled into negatively charged nanoparticles with a hybrid core of PLGA and PGlu, and a stealth PEG shell.
View Article and Find Full Text PDFTo improve the oral absorption of insulin, a novel carrier of Vitamin B12 (VB12) gel core solid lipid nanopaticles (Gel-Core-SLN, GCSLN) was designed with a gel core, lipid matrix and VB12-coated surface. VB12-stearate was synthesized and characterized by infrared spectroscopy (IR), nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS). Sol-gel conversion following ultrasonic heating and double emulsion technology were combined to implant the insulin-containing gel into solid lipid nanoparticles (SLN).
View Article and Find Full Text PDFIn this study, to enhance the dissolution rate and oral bioavailability of bifendate, a silica-supported solid dispersion (SD) of bifendate was prepared using supercritical carbon dioxide (ScCO2) technology. The properties of bifendate-silica SD were characterized by differential scanning calorimetry (DSC), X-ray diffraction (X-RD) and scanning electron microscopy. The pharmacokinetic study was carried out in beagle dogs using commercial bifendate dropping pills as a reference which is a conventional SD formulation of bifendate and PEG6000.
View Article and Find Full Text PDFThe main purpose of this study was to investigate the feasibility of azithromycin (AZI)--Aerosil 200 solid dispersions specifically with high stability under accelerated condition (40 °C/75% RH). Ball milling (BM) and hot-melt extrusion (HME) were used to prepare AZI solid dispersions. The physical properties of solid dispersions were evaluated by differential scanning calorimetry (DSC), scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FT-IR) and thermogravimetric analysis (TGA).
View Article and Find Full Text PDFIn this study, monomethoxy (polyethylene glycol)-b-P (d,l-lactic-co-glycolic acid)-b-P (l-glutamic acid) (mPEG-PLGA-PGlu) nanoparticles with the ability to rapidly respond to the endolysosomal pH and hydrolase were prepared and the pH-sensitivity was tuned by adjusting the length of the PGlu segment. The mPEG5k-PLGA20k-PGlu (60) nanoparticles were specifically responsive to an endosomal pH of 5.0-6.
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