Preparation and in vitro evaluation of a polymer based controlled release dry powder inhaler formulation for pulmonary delivery

This thesis described the synthesis of an L-leucine conjugate of the biodegradable polymer, chitosan and its potential application for the development of controlled release nanoparticulate dry powder inhaler (DPI) formulations. The study demonstrated that the physicochemical properties of conjugated chitosan nanoparticles had favourable effects on the dispersibility and controlled release profile of a model drug. The toxicity profile of the nanoparticulate formulation revealed promising outcome for its use in pulmonary delivery. The chitosan conjugate produced in this project would be useful for the application of polymer nanoparticulate systems for efficient lung delivery of drugs.

Non-specific conducting polymer-based array capable of monitoring odour emissions from a biofiltration system in a piggery building

A commercial non-specific gas sensor array system was evaluated in terms of its capability to monitor the odour abatement performance of a biofiltration system developed for treating emissions from a commercial piggery building. The biofiltration system was a modular system comprising an inlet ducting system, humidifier and closed-bed biofilter. It also included a gravimetric moisture monitoring and water application system for precise control of moisture content of an organic woodchip medium. Principal component analysis (PCA) of the sensor array measurements indicated that the biofilter outlet air was significantly different to both inlet air of the system and post-humidifier air. Data pre-processing techniques including normalising and outlier handling were applied to improve the odour discrimination performance of the non-specific gas sensor array. To develop an odour quantification model using the sensor array responses of the non-specific sensor array, PCA regression, artificial neural network (ANN) and partial least squares (PLS) modelling techniques were applied. The correlation coefficient (r(2)) values of the PCA, ANN, and PLS models were 0.44, 0.62 and 0.79, respectively.

Supermacroporous Polymer-Based Cryogel Bioreactor for Monoclonal Antibody Production in Continuous Culture Using Hybridoma Cells

Cryogel matrices composed of different polymeric blends were synthesized, yielding a unique combination of hydrophilicity and hydrophobicity with the presence or absence of charged surface. Four such cryogel matrices composed of polyacrylamide-chitosan (PAAC), poly(N-isopropylacrylamide)-chitosan, polyacrylonitrile (PAN), and poly(N-isopropylacrylamide) were tested for growth of different hybridoma cell lines and production of antibody in static culture. All the matrices were capable for the adherence of hybridoma cell lines 6A4D7, B7B10, and H9E10 to the polymeric surfaces as well as for the efficient monoclonal antibody (mAb) production. PAAC proved to be relatively better in terms of both mAb production and cell growth. Further, PAAC cryogel was designed into three different formats, monolith, disks, and beads, and used as packing material for packed-bed bioreactor. Longterm cultivation of 6A4D7 cell line on PAAC cryogel scaffold in all the three formats could be successfully done for a period of 6 weeks under static conditions. Continuous packed-bed bioreactor was setup using 6A4D7 hybridoma cell line in the three reactor formats. The reactors ran continuously for a period of 60 days during which mAb production and metabolism of cells in the bioreactors were monitored periodically. The monolith bioreactor performed most efficiently over a period of 60 days and produced a total of 57.5 mg of antibody in the first 30 days (in 500 mL) with a highest concentration of 115 mu g mL(-1), which is fourfold higher than t-flask culture. The results demonstrate that appropriate chemistry and geometry of the bioreactor matrix for cell growth and immobilization can enhance the reactor productivity. (C) 2010 American Institute of Chemical Engineers Biotechnol. Prog., 27: 170-180, 2011

Polymer based photo detectors

Recent developments in our laboratory related to polymer-based light sensors are reviewed. The inherent processibility of the active polymer medium is utilized in the implementation of different designs for the opto-electronic applications. The utility of these devices as sensitive photodetectors, image sensors and position sensitive detectors is demonstrated. The schottky-type layer formation at interfaces of polymers such as polyalkylthiophenes and aluminum accompanied by the enhanced photo-induced charge separation due to high local electric field is tapped for some of these device structures. The sensitivity of polymer-based field effect transistors to light also provides a convenient lateral geometry for efficient optical-coupling and control of the transistor state. ne range of these polymer-detectors available with the option of operating in the diode and transistor modes should be an attractive feature for many potential applications.

Synthesis and characterization of photorefractive polymer based on chemically hybridized CdS-PVK nanocomposite with a new azo chromophore

We report an organic/inorganic polymer composite based on the chemically hybridized photoconductor CdS-PVK nanocomposite doped with a new second-order optically nonlinear chromophore 1-n-butoxy-2-methyl-(4-p-nitrophenylazo)benzene (BMNPAB) and plasticizer 9-ethyl-carbazole (ECZ) to manifest a photorefractive (PR) effect. A detailed description of the synthesis and characterization of BMNPAB is presented. The poled film including PVK-10-CdS nanocomposite and BMNPAB exhibits a high second harmonic generation (SHG) coefficient of 31 pm/V The photoconductivity of PVK-CdS nanocomposite also was studied here. Two-beam coupling experiment clearly indicated an asymmetric optical energy exchange between two beams on the polymer composite at zero electrical field, and the two-beam coupling gain of 50.0 cm(-1) and diffraction efficiencv of 4.2% were obtained at 647.1 nm wavelength. (C) 2007 Elsevier Ltd. All rights reserved.

Development of a Cationic Mucic Acid Polymer-Based Nanoparticle siRNA Delivery System

Cancer chemotherapy has advanced from highly toxic drugs to more targeted treatments in the last 70 years. Chapter 1 opens with an introduction to targeted therapy for cancer. The benefits of using a nanoparticle to deliver therapeutics are discussed. We move on to siRNA in particular, and why it would be advantageous as a therapy. Specific to siRNA delivery are some challenges, such as nuclease degradation, quick clearance from circulation, needing to enter cells, and getting to the cytosol. We propose the development of a nanoparticle delivery system to tackle these challenges so that siRNA can be effective.

Chapter 2 of this thesis discusses the synthesis and analysis of a cationic mucic acid polymer (cMAP) which condenses siRNA to form a nanoparticle. Various methods to add polyethylene glycol (PEG) for stabilizing the nanoparticle in physiologic solutions, including using a boronic acid binding to diols on mucic acid, forming a copolymer of cMAP with PEG, and creating a triblock with mPEG on both ends of cMAP. The goal of these various pegylation strategies was to increase the circulation time of the siRNA nanoparticle in the bloodstream to allow more of the nanoparticle to reach tumor tissue by the enhanced permeation and retention effect. We found that the triblock mPEG-cMAP-PEGm polymer condensed siRNA to form very stable 30-40 nm particles that circulated for the longest time – almost 10% of the formulation remained in the bloodstream of mice 1 h after intravenous injection.

Chapter 3 explores the use of an antibody as a targeting agent for nanoparticles. Some antibodies of the IgG1 subtype are able to recruit natural killer cells that effect antibody dependent cellular cytotoxicity (ADCC) to kill the targeted cell to which the antibody is bound. There is evidence that the ADCC effect remains in antibody-drug conjugates, so we wanted to know whether the ADCC effect is preserved when the antibody is bound to a nanoparticle, which is a much larger and complex entity. We utilized antibodies against epidermal growth factor receptor with similar binding and pharmacokinetics, cetuximab and panitumumab, which differ in that cetuximab is an IgG1 and panitumumab is an IgG2 (which does not cause ADCC). Although a natural killer cell culture model showed that gold nanoparticles with a full antibody targeting agent can elicit target cell lysis, we found that this effect was not preserved in vivo. Whether this is due to the antibody not being accessible to immune cells or whether the natural killer cells are inactivated in a tumor xenograft remains unknown. It is possible that using a full antibody still has value if there are immune functions which are altered in a complex in vivo environment that are intact in an in vitro system, so the value of using a full antibody as a targeting agent versus using an antibody fragment or a protein such as transferrin is still open to further exploration.

In chapter 4, nanoparticle targeting and endosomal escape are further discussed with respect to the cMAP nanoparticle system. A diboronic acid entity, which gives an order of magnitude greater binding (than boronic acid) to cMAP due to the vicinal diols in mucic acid, was synthesized, attached to 5kD or 10kD PEG, and conjugated to either transferrin or cetuximab. A histidine was incorporated into the triblock polymer between cMAP and the PEG blocks to allow for siRNA endosomal escape. Nanoparticle size remained 30-40 nm with a slightly negative ca. -3 mV zeta potential with the triblock polymer containing histidine and when targeting agents were added. Greater mRNA knockdown was seen with the endosomal escape mechanism than without. The nanoparticle formulations were able to knock down the targeted mRNA in vitro. Mixed effects suggesting function were seen in vivo.

Chapter 5 summarizes the project and provides an outlook on siRNA delivery as well as targeted combination therapies for the future of personalized medicine in cancer treatment.

Dynamic modulation of detection window in conducting polymer based biosensors.

Here we demonstrate a novel application that employs the ion exchange properties of conducting polymers (CP) to modulate the detection window of a CP based biosensor under electrical stimuli. The detection window can be modulated by electrochemically controlling the degree of swelling of the CP associated with ion transport in and out of the polymer. We show that the modulation in the detection window of a caffeine imprinted polypyrrole biosensor, and by extension other CP based biosensors, can be achieved with this mechanism. Such dynamic modulation in the detection window has great potential for the development of smart biosensors, where the sensitivity of the sensor can be dynamically optimized for a specific test solution.

Polymer-based board-level optical interconnects

This paper provides an overview of the rationale behind the significant interest in polymer-based on-board optical links together with a brief review of recently reported work addressing certain challenges in this field. Polymer-based optical links have garnered considerable research attention due to their important functional attributes and compelling cost-benefit advantages in on-board optoelectronic systems as they can be cost-effectively integrated on conventional printed circuit boards. To date, significant work on the polymer materials, their fabrication process and their integration on standard board substrates have enabled the demonstration of numerous high-speed on-board optical links. However, to be deployed in real-world systems, these optoelectronic printed circuit boards (OE PCBs) must also be cost-effective. Here, recent advances in the integration process focusing on simple direct end-fire coupling schemes and the use of low-cost FR4 PCB substrates are presented. Performance of two proof-of-principle 10 Gb/s systems based on this integration method are summarised while work in realising more complex yet compact planar optical components is outlined. © 2011 IEEE.

Cost-effective 10 Gb/s polymer-based chip-to-chip optical interconnect

Board-level optical links are an attractive alternative to their electrical counterparts as they provide higher bandwidth and lower power consumption at high data rates. However, on-board optical technology has to be cost-effective to be commercially deployed. This study presents a chip-to-chip optical interconnect formed on an optoelectronic printed circuit board that uses a simple optical coupling scheme, cost-effective materials and is compatible with well-established manufacturing processes common to the electronics industry. Details of the link architecture, modelling studies of the link's frequency response, characterisation of optical coupling efficiencies and dynamic performance studies of this proof-of-concept chip-to-chip optical interconnect are reported. The fully assembled link exhibits a -3 dBe bandwidth of 9 GHz and -3 dBo tolerances to transverse component misalignments of ±25 and ±37 μm at the input and output waveguide interfaces, respectively. The link has a total insertion loss of 6 dBo and achieves error-free transmission at a 10 Gb/s data rate with a power margin of 11.6 dBo for a bit-error-rate of 10 -12. The proposed architecture demonstrates an integration approach for high-speed board-level chip-to-chip optical links that emphasises component simplicity and manufacturability crucial to the migration of such technology into real-world commercial systems. © 2012 The Institution of Engineering and Technology.

Multimode 90°-crossings, combiners and splitters for a polymer-based on-board optical bus

The design and characterization of polymer-based multimode 90°-crossings, combiners and splitters exhibiting excess losses below 0.1 dB/crossing, 2 dB and 3 dB respectively are reported. The devices enable the realization of an on-board optical bus. © 2012 OSA.

Multimode 90°-crossings, combiners and splitters for a polymer-based on-board optical bus

The design and characterization of polymer-based multimode 90°-crossings, combinersand splitters exhibiting excess losses below 0.1 dB/crossing, 2 dB and 3 dB respectively arereported. The devices enable the realization of an on-board optical bus. © OSA 2012.

Direct patterning of polymer-based photo luminescent structures with a mask

We report a simple method to directly pattern polymer-based photo luminescent material, i.e. a prepatterned mask is placed a close distance above it. The final structure is a positive replica of the lateral structures in the mask with submicrometer resolution. The comparison of luminescence efficiency before and after patterning indicates almost no degradation in optical property of the material during the experiments. The mechanism of pattern formation is also discussed.

SYNTHESIS AND CHARACTERIZATION OF A NEW COMB-LIKE POLYMER-BASED ON POLY(VINYL METHYL ETHER-ALT-MALEIC ANHYDRIDE) BACKBONE

A new comblike polymer host for polymer electrolyte was synthesized by reacting monomethyl ether of poly(ethylene glycol) with poly(vinyl methyl ether-alt-maleic anhydride) and endcapping the residual carboxylic acid with methanol. Butanone was selected as a solvent for the esterification in order to obtain a completely soluble product. The synthesis process was traced through by LR. Compared with the model compounds, the presumed structure of this comblike polymer has been proved to be valid by C-13 NMR The comb polymer is a white rubbery solid. It can be dissolved in butanone and THF, and manifests good film forming ability.

Molecularly imprinted polymer based on MWCNTs-QDs as fluorescent biomimetic sensor for specific recognition of target protein

A novel molecularly imprinted optosensing material based on multi-walled carbon nanotube-quantum dots (MWCNT-QDs) has been designed and synthesized for its high selectivity, sensitivity and specificity in the recognition of a target protein bovine serum albumin (BSA). Molecularly imprinted polymer coated MWCNT-QDs using BSA as the template (BMIP-coated MWCNT-QDs) exhibits a fast mass-transfer speed with a response time of 25 min. It is found that the BSA as a target protein can significantly quench the luminescence of BMIP-coated MWCNT-QDs in a concentration-dependent manner that is best described by a Stem-Volmer equation. The K-SV for BSA is much higher than bovine hemoglobin and lysozyme, implying a highly selective recognition of the BMIP-coated MWCNT-QDs to BSA. Under optimal conditions, the relative fluorescence intensity of BMIP-coated MWCNT-QDs decreases linearly with the increasing target protein BSA in the concentration range of 5.0 x 10(-7)-35.0 x 10(-7) M with a detection limit of 80 nM.