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Methicillin-resistant Staphylococcus aureus (MRSA) is an extensive origin of nosocomial infections that are very much challenging as well as complicated to eradicate mostly due to their strong resistance against all existing antibiotic therapies. Here the chitosan-grafted-polycaprolactone/maleic anhydride-pyrazinamide (CS-g-PCL/MA-PZA) polymeric drug carrier constructed via dialysis for anti-MRSA drugs like rifampicin (RF) and pyrazinamide (PZA) delivery. Nearly 200 nm size of the spherical particle with −20.04 mV of zeta potential observed. The cumulative PZA and RF releases from the carrier were observed 83.25% and 76.54% respectively in pH 5.5, and the in vitro drug release profile demonstrates that the fabricated micelle was pH-responsive. For the intestinal colonization, an in vivo assay performed using C. elegans, and the CS-g-PCL/MA-PZA/RF micelles treated worms generally belong to the weakly colonized category. Therefore, the study revealed that CS-g-PCL/MA-PZA/RF micelle could be a promising approach for therapeutic applications to achieve efficient anti-MRSA drug delivery.

Here, we focus on the fabrications of an osteosarcoma implant for bone repair via the development of a hydroxyapatite/κ-carrageenan-maleic anhydride/casein with doxorubicin (HAP/κ-CA-MA-CAS/DOX) composite-deposited titanium (Ti) plate. The HAP/κ-CA-MA-CAS/DOX material was coated on the Ti plate through the EPD method (electrophoretic deposition), applying direct current (DC) signals to deposit the composite on the surface of the Ti plate. The physicochemical and morphological possessions and biocompatibility in vitro of the prepared nanocomposite were examined to assess its prospective effectiveness for purposes of bone regeneration. Excellent biocompatibility and elevated osteoconductivity were confirmed using MG63 osteoblast-like cells. In vivo studies were performed at tibia sites in Wistar rats, and rapid bone regeneration was detected at four weeks in defective bone. Overall, the studies demonstrate that the HAP/κ-CA-MA-CAS/DOX composite enhances the biocompatible and cell-stimulating biointerface of Ti metallic implants. As such, HAP/κ-CA-MA-CAS/DOX implants are viable prospects for osteosarcoma-affected bone regeneration.

The potential of polymeric micelles constructed by coalescing natural and synthetic polymers for tuberculosis (TB) treatment was evaluated in this work. We designed a polymeric micelle to improve the delivery of anti-TB drugs (rifampicin [RF] and isoniazid [INH]). The polymeric core was synthesized in the following order: initially chitosan (CS) was grafted with polycaprolactone (PCL) to form CS-g-PCL followed by amide bond formation with maleic anhydride-isoniazid (MA-INH); finally, CS-g-PCL was conjugated with the MA-INH moiety to form the CS-g-PCL/MA-INH polymeric core. Another anti-TB drug, RF, was loaded onto CS-g-PCL/MA-INH through dialysis. The changes in the nature of functional groups and crystallinity were investigated by Fourier transform infrared spectroscopy and X-ray diffraction analysis, respectively. The shape and size of CS-g-PCL/MA-INH and RF-CS-g-PCL/MA-INH were analyzed by dynamic light scattering, scanning electron microscopy, and transmission electron microscopy. The cumulative drug release profiles were measured by UV-visible spectrophotometry and HPLC analysis. The antimicrobial activity of the loaded micelles was evaluated by finding the minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and bacterial cell rupture analyses. The nontoxic nature of the micelles was assessed by ex vivo studies on U937 and L929 cell lines and erythrocytes by performing an MTT assay, apoptosis assay, and hemolysis assay. Ex vivo cellular uptake and in vivo internalization of the INH- and RF-containing micelles were tested on U937 cells and zebrafish using fluorescence microscopy analysis. All of the observations indicate that the multi-TB drug-loaded polymeric micelle is a safe and effective system for the delivery of anti-TB drugs without affecting the mycobactericidal activity.

Polysaccharides are increasingly used as biodegradable nanocarrier to selectively deliver therapeutic agents to specific cells. In this study, maleate gellan gum (MA-GG) formed by addition of free radical polymerizable groups, which can be polymerized presence of acetone to design biodegradable three-dimensional networks, were synthesized by esterification. Natural silk sericin was grafted over the maleate gellan gum surface. Maleate Gellan Gum- Silk Sericin-Chitosan (MA-GG-SS-CS) nanocomposites loaded with rifampicin (RF) and pyrazinamide (PZA) to overcome the problems associated with Tuberculosis (TB) therapy. The pH responsive behavior of gellan gum nanocomposites was reposed by silk sericin and exhibited sustained release of 79% RF and 82% PZA for 120 h at pH 4.0. The designed formulations shows higher antimycobacterial activity and rapid delivery of drugs at TB infected macrophage. Nanomaterial effectively aggregated and internalized into the bacterial cells and MH-S cells. Dual drug release inside the cells makes damage in the cell membrane. Green nanocomposites studies pave the way for important use of macromolecules in pulmonary delivery TB drugs. (C) 2018 Elsevier B.V. All rights reserved.

Natural polymer guar gum has one of the highest viscosities in water solution and hence, these are significantly used in pharmaceutical applications. Guar gum inter-connected micelles as a new carrier has been developed for poor water soluble rifampicin drug. The hydrogel inter-connected micelle core was formulated as a hydrophilic inner and hydrophobic outer core by using guar gum/chitosan/polycaprolactone and the carrier interaction with rifampicin was confirmed by FT-IR. The morphological observations were carried out through TEM, SEM and AFM analysis. The encapsulation efficiency and in-vitro drug release behavior of prepared hydrogel based micelle system was analyzed by UV–vis spectrometry. The anti-bacterial activity against K. pneumoniae and S. aureus was studied by observing their ruptured surface by SEM. The cytotoxicity study reveals that the pure polymeric system has no toxic effect whereas drug loaded ones showed superior activity against THP-1 cells. From the cell apoptosis analyses, the apoptosis was carried out in a time dependent manner. The cell uptake behavior was also observed in THP-1 cells which indicate that the hydrogel based micelle system is an excellent material for the mucoadhesive on intracellular alveolar macrophage treatment.

To improve the performance of drug delivery systems in macrophages, targeted ligand-conjugated polymeric carriers have been realized to be vital for targeted, sustainable and controlled drug release with remarkable biocompatibility and bioavailability. The primary goal of the present study was to fabricate a multi-layered polymeric nanocarrier system with a targeting moiety for the release of multiple drugs (rifampicin and isoniazid) for pulmonary tuberculosis. In this regard, sodium alginate-grafted allylamine-rifampicin and chitosan-grafted allylamine-mannose were obtained as nano-sized materials by a simple and facile method. A series of physiochemical characterizations via FTIR, XRD, SEM, TEM, and AFM were performed to characterize and confirm the structure and shape of the nanocarriers. Via in vitro drug release studies, the patterns of release of rifampicin and isoniazid in response to a lysozyme environment were observed. Biological evaluations of the prepared nanopolymeric systems have been investigated by cell cytotoxicity, cellular uptake, and intracellular protein leakage and confirmed that future clinical applications of these materials in the field of tuberculosis are feasible.

This study demonstrates the development of pH and thermosresponsive nanoparticles (NPs) composed via cholic acid, PCPP-PLA hybrid polymer integrated with indocyanine green (ICG) for site specific delivery hydrophobic drug (paclitaxel). Drug and ICG were physically encapsulated by poly (bis(carboxyphenoxy)phosphazene) (PCPP)-poly lactic acid hybrid polymer. The hybrid polymer solution showed reversible gelation behaviour at the temperature between 37 °C and 20 °C and also it showed pH dependent drug release capability at acidic pH due to the pH responsive quenching effects of PCPP-PLA. The size (150–200 nm) and morphology of drug-loaded polymeric NPs were characterized using SEM and HR-TEM. Further, the release of loaded paclitaxel (PTX) from polymer was significantly sustained over 12 days. Drug release from the nanoparticles was effectively controlled by the mechanical strength of the polymer. All of these results demonstrate that pH triggered hybrid polymeric NPs are potential carriers for tumor-targeted drug delivery and also it exhibits great strength at 37 °C.

The delivery of drugs in nanosized carriers arises as a very attractive solution. This study reports the in vitro cytotoxic effect of palbociclib loaded chitosan cross-linked polypropylene glycol nanocarriers. The nanocarriers were prepared by ion gelation using calcium chloride, calcium oxalate, and sodium tripolyphosphate as cross-linking agents. The influence of the cross-linking agent on the size and morphology of the chitosan- polypropylene glycol nanocarriers was studied by Dynamic Light Scattering (DLS), Scanning Electron Microscope (SEM), and Atomic Fluorescence Microscope (AFM). Tripolyphosphate assisted carriers was found higher amount palbociclib encapsulation capacity compared with other two carriers. The drug releasing behavior was studied at pH 6.8 which was based on the bulk erosion principal of the carriers. Palbociclib loaded chitosan-polypropylene glycol carriers were found to show excellent drug releasing kinetics and biocompatibility in in-vitro analysis. The unloaded chitosan-polypropylene glycol carrier was identified to have less inherent cytotoxicity, whereas the loaded carriers are as active as equal to pure palbociclib against the MCF-7 cancer cell line. The palbociclib loaded nanocarriers were studied to determine their potential anticancer activity against the MCF-7 cell line. The IC50 values of three carriers chitosan-polypropylene glycol -I, chitosan-polypropylene glycol -II and chitosan-polypropylene glycol -III was observed 55.4, 51.0 and 38.7 mg/μL respectively. The effect of palbociclib uptake was evaluated by confocal microscopy using acridine orange/ethidium bromide and 4, 6-diamidino-2-phenylindole staining. Palbociclib loaded chitosan-polypropylene glycol nanocarriers show promise as potential candidates for cancer therapeutic applications.

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 (

Biocompatible polymers and ceramic materials have been identified as vital components to fabricate drug delivery and tissue engineering applications because of their high drug loading capability, sustained release and higher mechanical strength with remarkable in-vivo bioavailability. In the present work, initially we designed κ-carrageenan grafted with maleic anhydride and then reacted it with isoniazid drug (κ-Car-MA-INH). The polymeric system was cross linked with nanohydroxyapatite (NHAP) via electrostatic interaction followed by the addition of rifampicin (RF) and loaded to fabricate κ -Car-MA-INH/NHAP/RF nanocomposites. The chemical modification and interaction of drug with the polymeric–ceramic system were characterised by Fourier Transform Infrared spectroscopy (FT-IR). The zeta potential of the κ -Car-MA-INH/NHAP/RF nanocomposite was observed to be −20.04 mV using Zetasizer. The in vitro drug release studies demonstrated that the nanocomposite releases 76% of RF and 82% of INH in 12 days at pH 5.5. Scanning Electron Microscope analysis revealed the structural deformation of Staphylococcus aureus and Klebsiella pneumoniae upon treatment with this nanocomposite. By using ex-vivo studies combined with physio-chemical characterization methods on the erythrocytes, L929 and MG-63 cell lines, this composite was found to be biocompatible, non-cytotoxic and inducing cell proliferation with less significant hemolysis. Thus, our modified drug delivery nanocomposites afforded higher drug bioavailability with large potential for fabrication as long-acting drug delivery nanocomposites, especially with hydrophobic drugs inducing the growth of osteoblastic bone cells.

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. Scopus

Amphiphilic chitosan-graft-poly(caprolactone)/(ferulic acid) (CS-g-PCL/FA) multi-co-polymers were fabricated by microwave-assisted ring opening polymerization followed by an 1-ethyl-3-(3-dimethyl-aminopropyl) carbodiimide (EDC)-mediated coupling reaction and characterized by Fourier transformed infrared (FTIR) spectroscopy. Graft copolymers self-assembled into nanomicelles, and were able to incorporate rifampicin (RF) into their hydrophobic inner cores. X-ray diffraction (XRD) patterns were applied to characterize the crystal structures of graft polymers and the effects of RF on micelle morphology. Empty and RF-loaded CS-g-PCL/FA nanomicelles underwent swelling and degradation in acidic pH conditions. Scanning electron microscopy, transmission electron microscopy, and dynamic light scattering revealed that the self-assembled, RF-loaded micelles were spherical, with an average size of 100–210 nm. An in vitro study conducted at 37 °C demonstrated that RF and FA release from micelles at pH 5.3 was much faster than that at pH 7.4. The RF and FA release was significantly accelerated by switching to an acidic pH, owing to swelling of the micelles at lower pH values caused by the rapid degradation of ester and amide bonds present in the micelles. Fluorescence micrographs revealed successful entry of the polymeric micelles into A549cell lines. Thus, graft polymeric micelles have promising potential for delivery of hydrophobic antitubercular drugs and may improve therapeutic approaches for tuberculosis.

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. Scopus