Chlorin e6 decorated doxorubicin encapsulated chitosan nanoparticles for photo-controlled cancer drug delivery.

In the study we have reported the physico-chemical, photophysical and morphological properties of chlorin e6 (Ce6) decorated doxorubicin (DOX) encapsulated chitosan (CS)-tripolyphosphate (TPP) nanoparticles which prepared by ionotropic gelation method. The Ce6 physically loaded onto the nanoparticles by self-assembly of CS with TPP-DOX under aqueous conditions. The results from DLS studies highlights the prepared nanoparticles that possess the size in the range of 80-120 nm. with negatively charged of -6 mV. The SEM and AFM images showed 80-120 nm size while the average size of the Ce6 decorated nanoparticles was found to be around 100-130 nm. The absorption spectra of Ce6 decorated nanoparticles are similar when compared to free Ce6 which suggest there is no change in the Ce6 chromophore upon decoration. This nanoparticle showed high photostability and singlet oxygen generation (SOG). The Ce6 decorated and DOX encapsulated nanoparticles sizes and charges are in the range of 90-130 nm and -30 mV respectively. The nanoparticles showed high encapsulation efficiency towards DOX as well as pH controlled release. This has significant anti-proliferative activity against MCF-7 breast cancer cells after irradiation at near infra-red (NIR) ranges were evaluated. This could have potential applications in photo-controlled smart DOX delivery system for cancer treatment.

Design of biostable scaffold based on collagen crosslinked by dialdehyde chitosan with presence of gallic acid.

In this study, we have prepared the biostable collagen scaffold which is crosslinked by dialdehyde chitosan (DAC) with presence of Gallic acid (GA) and characterized its physico-chemical, biostable and biocompatible properties. The digital photographic and scanning electron microscopic (SEM) images of the prepared collagen scaffold is exposed well with properly oriented interconnected porous natured structure. The appearance of diffraction peaks showed slightly crystalline characteristic when compared to others. The differential scanning calorimetric (DSC) and thermogravimetric analysis (TGA) measurements indicates well significantly increased denaturation temperature (TD) and decreased decomposition rate. FT-IR result suggests the structural integrity of collagen which favours the molecular stability. The dialdehyde groups from DAC crosslinked with collagen functional groups that increase the molecular crosslinking owing to the large number of amino groups in its molecular chain. This scaffold exhibited 87% resistance against collagenolytic degradation by collagenase. The results showed that the improved biostability which prevents the free access of the collagenase to binds with the collagen triple helical chains. This scaffold confirm high biocompatibilities; enhanced cell proliferation and adhesions properties. This results gains new insight into the collagen scaffold to improves the biostability. This could be suitable method to preparation of collagenous biomaterials for tissue engineering applications.

Experimental and theoretical studies on Gallic acid assisted EDC/NHS initiated crosslinked collagen scaffolds.

The effect of Gallic acid (GA) in the presence of 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC)/N-hydroxysuccinimide (NHS) on collagen scaffold is investigated. The thermal mechanical analyzer (TMA), differential scanning calorimetric (DSC), and thermogravimetric analysis (TGA) including tensile strength (TS, 180 ± 3 MPa), denaturation temperature (Td, 80.03°C), % elongation (% E, 180 ± 9) and weight loss (31.76%), indicate that the modification improves the structural integrity and stability of the collagen scaffold. The GA-EDC/NHS treatment inhibits the action of collagenase against collagen degradation compared to GA and EDC/NHS. It is concluded from docking studies that GA binds with collagen like peptide (CLP) and collagenase through multiple H-bonds and hydrophobic interactions leading to low binding energy -5.1 and -5.3 Kcal/mol, respectively. The hydrophobic core of the GA molecules, probably incorporates itself into the hydrophobic areas of the collagen groups, whereas OH and COOH moieties of GA establish multiple H-bonds with neighboring collagen molecules and carboxamide bond, thereby improving the swelling and water uptake properties, biocompatibility and cell adhesion properties. This results in improving stability of the scaffold, which prevents the free access of the collagenase to reactive sites in the triple helical collagen chains.

Click chemistry approach to conventional vegetable tanning process: accelerated method with improved organoleptic properties.

Click chemistry approaches are tailored to generate molecular building blocks quickly and reliably by joining small units together selectively and covalently, stably and irreversibly. The vegetable tannins such as hydrolyzable and condensed tannins are capable to produce rather stable radicals or inhibit the progress of radicals and are prone to oxidations such as photo and auto-oxidation, and their anti-oxidant nature is well known. A lot remains to be done to understand the extent of the variation of leather stability, color variation (lightening and darkening reaction of leather), and poor resistance to water uptake for prolonged periods. In the present study, we have reported click chemistry approaches to accelerated vegetable tanning processes based on periodates catalyzed formation of oxidized hydrolysable and condensed tannins for high exhaustion with improved properties. The distribution of oxidized vegetable tannin, the thermal stability such as shrinkage temperature (T s) and denaturation temperature (T d), resistance to collagenolytic activities, and organoleptic properties of tanned leather as well as the evaluations of eco-friendly characteristics were investigated. Scanning electron microscopic analysis indicates the cross section of tightness of the leather. Differential scanning calorimetric analysis shows that the T d of leather is more than that of vegetable tanned or equal to aldehyde tanned one. The leathers exhibited fullness, softness, good color, and general appearance when compared to non-oxidized vegetable tannin. The developed process benefits from significant reduction in total solids and better biodegradability in the effluent, compared to non-oxidized vegetable tannins.

Novel collagen scaffolds prepared by using unnatural D-amino acids assisted EDC/NHS crosslinking.

This work discusses the preparation and characterization of novel collagen scaffolds by using unnatural D-amino acids (Coll-D-AAs)-assisted 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC)/N-hydroxyl succinimide(NHS)-initiated crosslinking. The mechanical strength, hydrothermal and structural stability, resistance to biodegradation and the biocompatibility of Coll-D-AAs matrices were investigated. The results from Thermo mechanical analysis, Differential scanning calorimetric analysis and Thermo gravimetric analysis of the Coll-D-AAs matrices indicate a significant increase in the tensile strength (TS, 180±3), % elongation (% E, 80±9), elastic modulus (E, 170±4) denaturation temperature (T d, 108±4) and a significant decrease in decomposition rate (Tg, 64±6). Scanning electron microscopic and Atomic force microscopic analyses revealed a well-ordered with properly oriented and well-aligned structure of the Coll-D-AAs matrices. FT-IR results suggest that the incorporation of D-AAs favours the molecular stability of collagen matrix. The D-AAs stabilizing the collagen matrices against degradation by collagenase would have been brought about by protecting the active sites in collagen. The Coll-D-AAs matrices have good biocompatibility when compared with native collagen matrix. Molecular docking studies also indicate better understanding of bonding pattern of collagen with D-AAs. These Coll-D-AAs matrices have been produced in high mechanical strength, thermally and biologically stable, and highly biocompatible forms that can be further manipulated into the functional matrix suitable in designing scaffolds for tissue engineering and regenerative medical applications.

Development of D-lysine-assisted 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide/N-hydroxysuccinimide-initiated cross linking of collagen matrix for design of scaffold.

This work discusses the preparation and characterization of collagen scaffold with presence of D-Lysine (Coll-D-Lys)-assisted 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC)/N-hydroxysuccinimide (NHS)-initiated cross linking. The mechanical strength, thermal and structural stability, resistance to biodegradation and cell viability of this scaffold was investigated. The results of the Coll-D-Lys-EDC/NHS scaffold also indicate an increase in the tensile strength (T(S)), percentage of elongation (% E), denaturation temperature (T(d)), and decrease the decomposition rate. Scanning electron microscopic (SEM) and atomic force microscopic (AFM) analyses revealed a well ordered with properly oriented and well-aligned structure of scaffold. The D-Lys stabilizes the scaffold against degradation by collagenase than L-Lys. The cell assay showed more than 98 ± 2% fibroblast viability (NIH 3T3) after 72 h of culture Coll-D-Lys-scaffold when compared with native Coll and Coll-L-Lys-scaffold. The proteolytic machinery is not well equipped to deal with Coll-D-Lys-scaffold than Coll-L-Lys-scaffold. Incorporating D-Lys in scaffold design has the potential to improve existing collagen stability and create new topologies inaccessible to homochiral molecules. This method may assist in the functionalization of the scaffold for regenerative applications.

Studies on collagen-tannic acid-collagenase ternary system: Inhibition of collagenase against collagenolytic degradation of extracellular matrix component of collagen.

We report the detailed studies on the inhibitory effect of tannic acid (TA) on Clostridium histolyticum collagenase (ChC) activity against degradation of extracellular matrix component of collagen. The TA treated collagen exhibited 64% resistance against collagenolytic hydrolysis by ChC, whereas direct interaction of TA with ChC exhibited 99% inhibition against degradation of collagen and the inhibition was found to be concentration dependant. The kinetic inhibition of ChC has been deduced from the extent of hydrolysis of N-[3-(2-furyl) acryloyl]-Leu-Gly-Pro-Ala (FALGPA). This data provides a selective competitive mode of inhibition on ChC activity seems to be influenced strongly by the nature and structure of TA. TA showed inhibitor activity against the ChC by molecular docking method. This result demonstrated that TA containing digalloyl radical possess the ability to inhibit the ChC. The inhibition of ChC in gaining new insight into the mechanism of stabilization of collagen by TA is discussed.