Sustained drug release from multi-layered sequentially crosslinked electrospun gelatin nanofiber mesh

The aim of this study is to develop electrospun gelatin nanofibers based drug delivery carrier to achieve controlled and sustainable release of hydrophobic drug (piperine) for prolonged time. To accomplish this, we devised some strategies such as sandwiching the drug loaded gelatin nanofiber mesh with another gelatin nanofiber matrix without drug (acting as diffusion barrier), sequential crosslinking and finally, a combination of both. As fabricated multilayered electrospun nanofibers mesh was first characterized in terms of degradation study, morphology, drug-polymer interactions, thermal stability followed by studying their release kinetics in different physiological pH as per the gastrointestinal tract. Our results show that with optimized diffusional barrier support and sequential crosslinking together, a zero order sustained drug release up to 48 h may be achieved with a flexibility to vary the drug loading as per the therapeutic requirements. This work lays out the possibility of systematic design of multilayer nano-fiber mesh of a biopolymer as a drug delivery vehicle for hydrophobic drugs with a desired signature of zero order release for prolonged duration

Controlled Branching of Industrially Important Polymers: Modeling and Multi-objective Optimization

Long chain branching (LCB) in any polymerization is of profound importance. It helps in improving certain properties such as melt strength and strain hardening. Branched polymers are, therefore, having different characteristics than linear polymers. In addition to having good end use properties, they are well suited for various processing applications such as blow molding, thermoforming, extrusion coating etc. As real world applications demand different extents of branching of polymers for different applications, this study aims to perform an investigation for a controlled way of long chain branching of polymers with enhanced properties. The main goal of this research is, therefore, three fold; viz. i) Finding the optimal process conditions for the desired combination of conflicting objectives, ii) Development of a kinetic model for long chain branched polypropylene system based on the available experimental data from open literature and simultaneously performing the multi objective optimization for the desired combination of conflicting performance objectives within experimental limits, and iii) Development of Kriging based surrogate model to replace the first principles based computationally expensive model to save execution time, while performing the multi objective optimization task for a highly non-linear, multi-modal search space. First, a batch optimization study for the bulk polymerization of vinyl acetate has been considered to find optimal process conditions for imparting LCB in polymer architecture. A theoretical study has been conducted with a validated model to observe the effect of live radical concentration on long chain branching as this is an important factor for branching in polymer molecule via ‘chain transfer to polymer’ route

Effect of Polyethylene Glycol, Glycerol and Sodium Chloride on Sodium Alginate and Gelatin blend – A molecular dynamics study

Sodium Alginate and Gelatin blends showed strong response towards the external stimuli of pH and ionic strengths. Molecular dynamics simulations were used to study the hydrogen bonding interactions in these blends when subjected to different pH and different ionic strength medium. The effect of plasticizers viz. glycerol and polyethylene glycols of different molecular weights on the blend were also studied. In addition, the effect of external stimuli and plasticizers upon the individual constituents of the blend viz. Sodium Alginate and Gelatin were also studied in order to understand their combined effect in the properties shown by the Sodium Alginate and Gelatin blend. Polyelectrolytic properties of sodium alginate and polyampholytic properties of gelatin were explored both in presence and absence of salt. Finally, the simulation results for gelatin in salt medium were verified using theoretical expressions and experimental analysis of the same system

Controlled Molecular Release through Polymeric Vehicle

Controlled drug delivery systems (DDS) have gained a lot of attention recently due to their added advantages such as improving therapeutic efficacy in delivering the drug molecules at a predetermined rate to the targeted site for a prolonged period. Designing a polymer based DDS involves an in-depth understanding of drug-carrier interactions, and good control over the parameters that can modulate transportation of drug molecules according to the therapeutic requirement. Delivering less soluble drug molecules encapsulated in hydrophilic polymer matrix in zero-order manner is usually a challenge. To counter this challenge, we used Piperine, a model hydrophobic drug and Amphotericin B (Amp-B), a model amphiphilic drug in order to develop a polymer based DDS. We also used FDA approved natural polymer gelatin (type A) as an excipient because of its biocompatibility, biodegradability, muco-adhesiveness and easy availability. Despite of all the advantages of gelatin, it is extremely hydrophilic and has poor mechanical stability in an aqueous solution that limits its application and long-term usage. To overcome this challenge, we used Glutaraldehyde (GTA) as a crosslinker to modify gelatin. Although GTA is widely used as a crosslinker because of its excellent efficiency in stabilizing collagenous material, higher concentration of GTA solution (25 % v/v) and longer exposure in saturated vapor of GTA (more than 24 h as reported in literature) may have adverse cytotoxic effects. We successfully used a highly diluted concentration of GTA solution (0.01-0.25 % v/v) and reduced the exposure time to only 6 minute to saturated GTA vapor for crosslinking to achieve the desired stability of the fabric. In summary, this thesis investigates the full potential of natural polymer (gelatin, type A) based cast-film (GCF) and electrospun nanofiber film (GNF) as DDS, particularly for less soluble drug molecules

Unveiling optimal operating conditions for an epoxy polymerization process using multi-objective evolutionary computation

The optimization of the epoxy polymerization process involves a number of conflicting objectives and more than twenty decision parameters. In this paper, the problem is treated truly as a multi-objective optimization problem and near-Pareto-optimal solutions corresponding to two and three objectives are found using the elitist non-dominated sorting GA or NSGA-II. Objectives, such as the number average molecular weight, polydispersity index and reaction time, are considered. The first two objectives are related to the properties of a polymer, whereas the third objective is related to productivity of the polymerization process. The decision variables are discrete addition quantities of various reactants e.g. the amount of addition for bisphenol-A (a monomer), sodium hydroxide and epichlorohydrin at different time steps, whereas the satisfaction of all species balance equations is treated as constraints. This study brings out a salient aspect of using an evolutionary approach to multi-objective problem solving. Important and useful patterns of addition of reactants are unveiled for different optimal trade-off solutions. The systematic approach of multi-stage optimization adopted here for finding optimal operating conditions for the epoxy polymerization process should further such studies on other chemical process and real-world optimization problems

Hofmeister series: An insight into its application on gelatin and alginate-based dual-drug biomaterial design

Alginate and gelatin are bio-polymers widely used in drug delivery. A range of salts can be used to achieve the required flexibility in biomaterial design. Hofmeister series gives an idea about the behaviour of salts with proteins. However, its application for the design of biomaterials and their specific effect on high-viscosity polymers and polymer mixtures has not quite been explored. Firstly, this work proposes a strategic interaction-based approach for designing a dual-drug ocular biomaterial. Secondly, the impact of different salt anions on gelatin and alginate mixture for the developed protocols is studied by a proposed method of determining shear-dependent general intrinsic viscosity. Thirdly, shear-dependent intrinsic viscosity is used to determine the interaction amongst the polymers in their mixture, which is then correlated to the release profiles and hydrodynamic radii of polymer mixtures. It is observed that Hofmeister anions behave reversely for high-viscosity negatively charged polymers and depends on the charge densities of the anions. For the polyelectrolyte/polyampholyte complex/mixture, the interactions depend on the addition sequence. It is inferred that the kosmotropes are preferred for protocols where salt is added between gelatin and alginate and chaotropes for protocols where salt is added to the gelatin and alginate complex/mixture in terms of release profiles

Bath induced phase transition in a Luttinger liquid

We study an XXZ spin chain, where each spin is coupled to an independent ohmic bath of harmonic oscillators at zero temperature. Using bosonization and numerical techniques, we show the existence of two phases separated by an Kosterlitz-Thouless (KT) transition. At low coupling with the bath, the chain remains in a Luttinger liquid phase with a reduced but finite spin stiffness, while above a critical coupling the system is in a dissipative phase characterized by a vanishing spin stiffness. We argue that the transport properties are also inhibited: the Luttinger liquid is a perfect conductor while the dissipative phase displays finite resistivity. Our results show that the effect of the bath can be interpreted as annealed disorder inducing signatures of localization.Comment: 11 pages, 4 figure

Soya nuggets – a potential carrier: swelling kinetics and release of hydrophobic drugs

In this study, soya nuggets were used as a potential drug delivery vehicle. This work includes the swelling study of soya nuggets followed by the morphology, chemical interactions, mechanical properties and release kinetics. Multiple drugs, both hydrophobic as well as hydrophilic were encapsulated and studied for drug release. This work aims at exploiting soya nuggets as a controlled drug release vehicle

In-vitro release study of hydrophobic drug using electrospun cross-linked gelatin nanofibers

Delivering hydrophobic drug within hydrophilic polymer matrix as carrier is usually a challenge. Here we report the synthesis of gelatin nanofibers by electrospinning, followed by testing them as a potential carrier for oral drug delivery system for a model hydrophobic drug, piperine. Electrospun gelatin nanofibers were crosslinked by exposing to saturated glutaraldehyde (GTA) vapor, to improve their water resistive properties. An exposure of only 6 min was not only adequate to control the early degradation with intact fiber morphology, but also significantly marginalized any adverse effects associated with the use of GTA. Scanning electron microscopy imaging, Fourier transform infrared spectroscopy and thermogravimetric analysis were done to study nanofiber morphology, stability of drug and effect of crosslinking. The pH of release medium was also varied as per the gastrointestinal tract for in-vitro drug release study. Results illustrate good compatibility of hydrophobic drug in gelatin nanofibers with promising controlled drug release patterns by varying crosslinking time and pH of release medium

IIT Hyb creates 'Kala Azar' or black fever treatment tablets with nanofibre controlled release mechanism

Indian Institute of Technology Hyderabad Researchers has developed a method to produce controlled-release oral tablets for treating fungal infections and leishmaniasis (kala azar or black fever) that are prevalent in the country. Their tablets were found to release the drug Amphotericin B in a sustained and controlled manner over a period of 10 days