Zn2+ cross-linked sodium alginate-g-allylamine-mannose polymeric carrier of rifampicin for macrophage targeting tuberculosis nanotherapy

Our aim was to evaluate the capacity of polymeric nanoparticles (PNPs) to selectively deliver an antituberculosis drug (rifampicin; RF) to alveolar macrophages. Anionic biodegradable copolymer sodium alginate-g-allylamine-mannose (SA-g-AA-M) was synthesized by atom transfer free radical polymerization and direct coupling of the respective conjugates. The fabrication of RF-loaded Zn2+ ion-cross-linked SA-g-AA-M PNPs was conducted by an O/W emulsion method followed by ionotropic gelation. The structural nature of the RF-loaded SA-g-AA-M PNPs was analyzed by Fourier transform infrared (FT-IR) spectroscopy. Meanwhile, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to illustrate the shape and morphology of the nanoparticles. The PNPs were observed as uniform spheres in the nanometer range (<300 nm), with a low polydispersity index, and excellent performance in terms of drug encapsulation and release ability. The PNPs also showed strong antimicrobial activities against Mycobacterium tuberculosis. Cytotoxicity evaluation in VERO cells by an MTT assay suggested that the PNPs have good biocompatibility. Alveolar macrophage targeting was evaluated via cellular uptake by A549 cells. The cellular uptake results revealed that the Zn2+ concentration of the PNPs increases the intracellular concentration of RF and enhances its antitubercular efficiency. Overall, the results suggest that PNPs could lead to the development of a possible mannose-containing carrier for a macrophage-targeting drug delivery system

Targeted delivery of rifampicin to tuberculosis-infected macrophages: design, in-vitro, and in-vivo performance of rifampicin-loaded poly(ester amide)s nanocarriers

We have developed a nano drug delivery system for the treatment of tuberculosis (TB) using rifampicin (RF) encapsulated in poly(ester amide)s nanoparticles (PEA-RF-NPs), which are biocompatible polymers. In this study, biodegradable amino acid based poly(ester amide)s (PEAs) were synthesized by the poly condensation reaction and RF-loaded NPs were fabricated by the dialysis method. The surface morphology and in-vitro drug release efficiency were examined. The effect of time and temperature on the cellular uptake of PEA-RF-NPs in NR8383 cells was evaluated. Fluorescence microscopic results of PEA-RF-NPs from NR8383 cell lines suggest its potential application in treating TB. The antibacterial activity of RF against Mycobacterium smegmatis was also evaluated. Based on these results, this approach provides a new means for controlled and efficient release of RF using the PEA-NPs delivery system and is promising for the treatment of TB.M. Rajan is grateful to the DST-SERB, Government of India, for financial support under the scheme of �EMEQ� (F.No.- SB/EMEQ-241-2014) and University Grants Commission UGC-MRP scheme Ref: No. F.43-187/2014 (SR), New Delhi. The authors would like to extend their sincere appreciation to the Deanship of Scientific Research at King Saud University for its funding of this research through Research Group project No. RG-1435-057. M. Rajan thanks the DST-FIST program for the purchase of an FTIR, SEM, and the UGC, for funds under UPE programs for the purchase of a TEM.Scopu

Surface functionalization of natural lignin isolated from: Aloe barbadensis Miller biomass by atom transfer radical polymerization for enhanced anticancer efficacy

Lignin (LIG), one of the major natural polymers in the biomass is widely used for various industrial and biomedical applications, mainly in its modified form of grafted lignin. The present study focuses on the isolation of lignin from Aloe barbadensis Miller by a microwave extraction technique and its applicability as a medicinal biomass. The isolated lignin was used for the synthesis of a drug carrier by grafting with methacrylate (MA). Lignin grafted methacrylate was synthesised (LIG-g-MA) via atom transfer radical polymerization (ATRP). 5-Fluorouracil (5-FU) was used as a model cancer drug and it was encapsulated on the hollow nanocarrier by the emulsion/solvent evaporation technique. While NMR spectroscopy elucidates the structure of the isolated lignin, FT-IR and XRD techniques address the binding nature and crystalline character of 5-FU loaded carrier. The surface morphology of the isolated lignin, grafted lignin and drug-loaded carrier was confirmed with SEM and TEM techniques. The encapsulation efficiency and in vitro drug release were studied to determine the efficiency of the carrier. The cell viability and cytotoxicity effect of 5-FU loaded on LIG-g-MA and unloaded LIG-g-MA were performed against MCF-7 and VERO cell lines. In short, the modified natural lignin based on LIG-g-MA hollow-nanofibrous material has been shown to be a potentially useful biocompatible nanocarrier in chemotherapy for cancer treatment. The Royal Society of Chemistry 2016.Scopu

A promising drug delivery candidate (CS-g-PMDA-CYS-fused gold nanoparticles) for inhibition of multidrug-resistant uropathogenic Serratia marcescens

Antibiotic resistance amongst microbial pathogens is a mounting serious issue in researchers and physicians. Various alternatives to overcome the multidrug-resistant bacterial infections are under search, and biofilm growth inhibition is one of them. In this investigation, a polymeric drug delivery system loaded with multi-serratial drugs to improve the delivery of drugs against urinary tract infection causative Serratia marcescens. The chitosan grafted pyromellitic dianhydride – cysteine (CS-g-PMDA-CYS) was conjugated with AuNPs by using the –SH group of CYS and RF (rifampicin) and INH (isoniazid) were loaded in AuNPs-fused CS-g-PMDA-CYS system. Several physicochemical techniques characterized this fabricated AuNPs/RF/INH/CS-g-PMDA-CYS system. The successful encapsulation of RF and INH in AuNPs-fused CS-g-PMDA-CYS polymer had confirmed, and it observed the loading capacity for RF and INH was 9.02% and 13.12%, respectively. The in vitro drug discharge pattern was perceived high in pH 5.5 compared with pH 7.4. The AuNPs/RF/INH/CS-g-PMDA-CYS escalates 74% of Caenorhabditis elegans survival during Serratia marcescens infection by aiming biofilm development and virulence in S. marcescens. Author postulate that the fabricated system is a promising drug carrier and delivery system for inhibition of multidrug-resistant bacterias like S. marcescens

Tuning the Potency of Farnesol-Modified Polyethylenimine with Polyanionic Trans-Booster to Enhance DNA Delivery

Low molecular weight polyethylenimine (PEI) based lipopolymers become an attractive strategy to construct nonviral therapeutic carriers with promising transfection efficiency and minimal toxicity. Herein, this paper presents the design and synthesis of novel farnesol (Far) conjugated PEI, namely PEI1.2k-SA-Far7. The polymers had quick DNA complexation, effective DNA unpacking (dissociation), and cellular uptake abilities when complexed with plasmid DNA. However, they were unable to provide robust transfection in culture, indicating inability of Far grafting to improve the transfection efficacy significantly. To overcome this limitation, the commercially available polyanionic Trans-Booster additive, which is capable of displaying electrostatic interaction with PEI1.2k-SA-Far7, has been used to enhance the uptake of pDNA polyplexes and transgene expression. pDNA condensation was successfully achieved in the presence of the Trans-Booster with more stable polyplexes, and in vitro transfection efficacy of the polyplexes was improved to be comparable to that obtained with an established reference reagent. The PEI1.2k-SA-Far7/pDNA/Trans-Booster ternary complex exhibited good compatibility with cells and minimal hemolysis activity. This work demonstrates the exemplary potency of using additives in polyplexes and the potential of resultant ternary complexes for effective pDNA delivery