Target-specific Drug Delivery Systems Research Articles

Carbon Nanomaterials for Biomedical Applications: Progress and Outlook.

Recent developments in nanoscale materials have found extensive use in various fields, especially in the biomedical industry. Several substantial obstacles must be overcome, particularly those related to nanostructured materials in biomedicine, before they can be used in therapeutic applications. Significant concerns in biomedicine include biological processes, adaptability, toxic effects, and nano-biointerfacial properties. Biomedical researchers have difficulty choosing suitable materials for drug carriers, cancer treatment, and antiviral uses. Carbon nanomaterials are among the various nanoparticle forms that are continually receiving interest for biomedical applications. They are suitable materials owing to their distinctive physical and chemical properties, such as electrical, high-temperature, mechanical, and optical diversification. An individualized, controlled, dependable, low-carcinogenic, target-specific drug delivery system can diagnose and treat infections in biomedical applications. The variety of carbon materials at the nanoscale is remarkable. Allotropes and other forms of the same element, carbon, are represented in nanoscale dimensions. These show promise for a wide range of applications. Carbon nanostructured materials with exceptional mechanical, electrical, and thermal properties include graphene and carbon nanotubes. They can potentially revolutionize industries, including electronics, energy, and medicine. Ongoing investigation and expansion efforts continue to unlock possibilities for these materials, making them a key player in shaping the future of advanced technology. Carbon nanostructured materials explore the potential positive effects of reducing the greenhouse effect. The current state of nanostructured materials in the biomedical sector is covered in this review, along with their synthesis techniques and potential uses.

Susceptibility of periodontal pathogens to a novel target-specific drug delivery system containing self-nanoemulsifying curcumin: An in vitro study.

Long-term use of many classic chemotherapeutic agents as adjuncts in the management of periodontitis has adverse complications, leading to seeking out naturopathic remedies. Although curcumin has been investigated in managing periodontitis, its therapeutic benefits have not been fully explored due to its limited solubility in an aqueous medium. This study aimed to develop a novel target-specific drug delivery system containing 1% self-nanoemulsifying curcumin (SNEC) in a hydroxypropylmethylcellulose (HPMC) matrix and evaluate the susceptibility of periodontal pathogens to this system in vitro. Its antibacterial activity against Tannerella forsythia, Porphyromonas gingivalis, Prevotella intermedia, and Aggregatibacter actinomycetemcomitans was evaluated and compared to pure nano-curcumin and SNEC alone by estimating their minimum inhibitory concentrations (MIC). The antibacterial activity of pure nano-curcumin, SNEC, and SNEC in HPMC against the four periodontal pathogens evaluated in terms of MIC was recorded in the range of 0.2‒0.4, 0.4‒0.8, and 0.2‒0.8 µg/mL, respectively. However, the MIC of all three curcumin formulations against the periodontal pathogens tested was higher than that of the standard moxifloxacin. While both pure nano-curcumin and SNEC showed increasing values of inhibition zones with increasing concentrations on disk diffusion assay, lower concentrations of SNEC in HPMC did not show a zone of inhibition against the tested pathogens. The novel delivery system containing SNEC in HPMC may be a potential adjunct in managing periodontitis due to its probable sustained antimicrobial activity against the tested periodontal pathogens.

The crosslink between the hyaluronic acid and drugs treated by reactive oxygen species produced in plasma based on the molecular dynamics simulation

Hyaluronic Acid (HA)-based pre-drugs can enable targeted drug delivery to cancer cells with CD44-high expressing, thus, it is essential to design an efficient, target specific drug delivery system based on HA. Plasma, as a simple and clean tool, has been widely used in the modification and crosslinking of biological materials in recent years. In this paper, we used the Reactive Molecular Dynamic (RMD) to explore the reaction between reactive oxygen species (ROS) in plasma and HA with drugs (PTX, SN-38, and DOX), in order to examine possible drug-coupled systems. The simulation results indicated the acetylamino groups in HA could be oxidized to unsaturated acyl groups, which offers the possibility of crosslinking. Three drugs also exposed the unsaturated atoms under the impact of ROS, which can cross-link directly to HA through CO and CN bonds, forming a drug coupling system with better release. This study revealed the exposure of active sites on HA and drugs by ROS impact in plasma, allowing us to study the crosslinking mechanism between HA and drugs at molecular level deeply, and also provided a new light for establishment of HA-based targeted drug delivery system.

Recent Advances in Targeted Nanocarriers for the Management of Triple Negative Breast Cancer

Triple-negative breast cancer (TNBC) is a life-threatening form of breast cancer which has been found to account for 15% of all the subtypes of breast cancer. Currently available treatments are significantly less effective in TNBC management because of several factors such as poor bioavailability, low specificity, multidrug resistance, poor cellular uptake, and unwanted side effects being the major ones. As a rapidly growing field, nano-therapeutics offers promising alternatives for breast cancer treatment. This platform provides a suitable pathway for crossing biological barriers and allowing sustained systemic circulation time and an improved pharmacokinetic profile of the drug. Apart from this, it also provides an optimized target-specific drug delivery system and improves drug accumulation in tumor cells. This review provides insights into the molecular mechanisms associated with the pathogenesis of TNBC, along with summarizing the conventional therapy and recent advances of different nano-carriers for the management of TNBC.

Prospects of Biosynthetically produced Nanoparticles in Biocontrol of Pests and Phytopathogens: A review

Modern nanotechnology is playing a vital role in our daily life by contributing in different domains such as usage of nanoparticles for target-specific drug delivery system, as these nanoparticle are being used as scratch proof coating on glass for tracking of biomolecules. Some emerging applications of nanoparticles include usage of nanoparticles for diagnostic purposes such as biomedical imaging and as green technology producing nano pesticides. The use of endophytic or plant beneficial bacteria for the production of metallic nanoparticles have shown promising results in not only controlling the pest but also contributing in enhanced developmental growth due to their small size, target specificity, and enhanced interaction with the plant in controlled environment. As for increasing environmental crisis, use of biological methods to remediate the environment is becoming a necessity. Green technology based nano-materials being used now a days in multiple fields, especially in bio-control of pests. This review is based on the microbial synthesized metallic nanoparticles, which are being used as nano pesticides (nanoparticles are pesticides).

Advancement of Targeted Drug Delivery Over Conventional Drug Delivery System Targeting to Colonic Region

Colon-targeted drug delivery is a wonderful drug delivery system targeting the lower parts of the GI tract to treat several colonic diseases such as inflammatory bowel diseases subdivided as ulcerative colitis, Crohn’s disease, amoebiasis, chronic diarrhea, colon cancer, vaginal infection, and bacterial infections, etc. A conventional drug delivery system can be referred to as a release of the drug, particularly to the targeted organ with a predetermined rate in a controlled manner. To achieve the prolonged therapeutic effect with predictable drug release kinetics, reduction of fluctuation in the steady-state concentration, increasing the therapeutic efficacy that convenient to patient and reduction of the patient compliance. Conventional drug delivery systems have some disadvantages which can be overcome by target-specific drug delivery systems. A targeted drug delivery system is a wonderful approach to target the pharmacological and therapeutical active moiety to target a specific region, and not to target non-targeted areas such as organ or tissue and accumulate to the targeting region only to show pharmacological activities. Some important criteria can be noticed under targeted drug delivery such as they are selectively and effectively targeting local as well as systemic regions and also involved in the pre-identified target can be set to deliver the active moiety, increase or enhancement of therapeutic concentration at the targeting region and accumulation of the active moiety to the target region and show high concentration, targeted drug delivery can enhancement of therapeutic activity with less adverse effect with less adverse events. The review discusses the advancement of targeted drug delivery over conventional drug delivery targeting the colonic environment to treat colonic diseases.

Microsponge as Novel Drug Delivery System: A Review

During the last few decades, pharmaceutical industry gave more importance to the controlled release of dosage forms like solid formulation, semi solid formulation, and topicalpreparation dueto efficacy and patient compliance. Normal topical preparations have some disadvantages like unpleasant odour, greasiness, and skin irritation reported in study cases. Also many topicalpreparations fail to reach the systemic circulation in sufficient amounts in few cases. This problem is achieved by the present formulation as microsponge in the areas of research. MDS is amicroscopic sphere capable of absorbing skin secretions, therefore reducing the oiliness of the skin. Microspongehaving particle size of 10-25 microns in diameter, have wide range of entrapmentof various ingredients in a single microsponges system and release them at desired rates.Microsponge is recent novel technique for control release and targetspecific drug delivery system. Microsponges are polymeric delivery system composed of porous microspheres. They are tiny sponge-like sphericalparticle with a large porous surface.Drug release in microsponge is done by the external stimuli like (pH, temperature, rubbing). It hasseveral advantageous over the other topical preparations are non allergenic, non toxic, non irritant, non mutagenic. Microsponges are designed to deliver apharmaceutical active ingredient efficiently at the minimum dose and alsoto enhance stability, reduce side effects and modify drug release.©2022iGlobal Research and PublishingFoundation. All rights reserved.

Targeted Drug Delivery: Trends and Perspectives.

Having various limitations in conventional drug delivery system, it is important to focus on the target-specific drug delivery system where we can deliver the drug without any degradation. Among various challenges that are thrown to a formulation scientist, delivering the drug to its right site, in its right dose, is also an important aim. A focused drug transport aims to extend, localize, target and have a safe drug interaction with the diseased tissue. The aim of targeted drug delivery is to make the required amount of the drug available at its desired site of action. Drug targeting can be accomplished in a number of ways that include enzyme mediation, pH-dependent release, use of special vehicles, receptor targeting, among other mechanisms. Intelligently designed targeted drug delivery systems also offer the advantages of a low dose of the drug along with reduced side effects which ultimately improves patient compliance. Incidences of dose dumping and dosage form failure are negligible. A focused drug transport aims to have a safe drug interaction with the diseased tissue. This review focuses on the available targeting techniques from experiment to perfection for delivery to the colon, brain, and other sites of interest. Overall, the article should make an excellent read for the researchers in this area. Newer drug targets may be identified and exploited for successful drug targeting.

Glycosylation of PAMAM dendrimers significantly improves tumor macrophage targeting and specificity in glioblastoma

Glioblastoma is among the most aggressive forms of cancers, with a median survival of just 15–20 months for patients despite maximum clinical intervention. The majority of conventional anti-cancer therapies fail due to associated off-site toxicities which can be addressed by developing target-specific drug delivery systems. Advances in nanotechnology have provided targeted systems to overcome drug delivery barriers associated with brain and other types of cancers. Dendrimers have emerged as promising vehicles for targeted drug and gene delivery. Dendrimer-mediated targeting strategies can be further enhanced through the addition of targeting ligands to enable receptor-specific interactions. Here, we explore the sugar moieties as ligands conjugated to hydroxyl-terminated polyamidoamine dendrimers to leverage altered metabolism in cancer and immune targeting. Using a highly facile click chemistry approach, we modified the surface of dendrimers with glucose, mannose, or galactose moieties in a well-defined manner, to target upregulated sugar transporters in the context of glioblastoma. We show that glucose modification significantly enhanced targeting of tumor-associated macrophages (TAMs) and microglia by increasing brain penetration and cellular internalization, while galactose modification shifts targeting away from TAMs towards galectins on glioblastoma tumor cells. Mannose modification did not alter TAMs and microglia targeting of these dendrimers, but did alter their kinetics of accumulation within the GBM tumor. The whole body biodistribution was largely similar between the systems. These results demonstrate that dendrimers are versatile delivery vehicles that can be modified to tailor their targeting for the treatment of glioblastoma and other cancers.

Mathematical Modeling and Simulations for Developing Nanoparticle-Based Cancer Drug Delivery Systems: A Review

Nanoparticles are crucial for developing patient-/target-specific drug delivery systems. In recent days, mathematical modeling and simulation plays an important role in optimization of various parameters like nanoparticle-based drug dose, dissolution of drug particles, and adverse reaction from the nanoparticles. With the help of modeling and simulation, we can determine or optimize the type, shape, and size of the nanoparticles to be utilized as potential drug delivery system and its influence on the targeted cells/tissues. The main purpose of this review article is to discuss the latest modeling and simulation tools available for developing patient-specific nanoparticle-based drug delivery systems. In our current study, we are reporting different mathematical models used for cancer drug delivery systems. It also reports several numerical methods, and simulations models are available for representing nano-drug-bio interactions within the biological systems. This review highlights the applications of mathematical modeling and simulation software for developing a rational nano-carrier design and selecting accurate biomaterials for in vivo model.

Mannose Conjugated Starch Nanoparticles for Preferential Targeting of Liver Cancer.

To design D-Mannose conjugated 5-Fluorouracil (5-FU) loaded Jackfruit Seed Starch Nanoparticles (JFSSNPs) for site-specific delivery. Liver cancer is the third leading cause of death in the world and the fifth most often diagnosed cancer. It is a major global threat to public health. Treatment of liver cancer with conventional method bears several side effects, thus to undertake these side effects as a formulation challenge, it is necessary to develop novel target-specific drug delivery system for the effective and better localization of drug into the proximity of target with restricting the movement of the drug in normal tissues. To optimize and characterize the developed D-Mannose conjugated 5-Fluorouracil (5- FU) loaded Jackfruit Seed Starch Nanoparticles (JFSSNPs) for effective treatment of liver cancer. 5-FU loaded JFSSNPs were prepared and optimized formulations having higher encapsulation efficiency were conjugated with D-Mannose. These formulations were characterized for size, morphology, zeta potential, X-Ray Diffraction, and Differential Scanning Calorimetry. The potential of NPs was studied using in vitro cytotoxicity assay, in vivo kinetic studies, and bio-distribution studies. 5-Fluorouracil loaded NPs had a particle size between 336 to 802 nm with drug entrapment efficiency between 64.2 to 82.3%. In XRD analysis, 5-FU peak was diminished in the diffractogram, which could be attributed to the successful incorporation of the drug in amorphous form. DSC study suggests there was no physical interaction between 5-FU and Polymer. NPs showed sustained in vitro 5-FU release up to 2 hours. In vivo, mannose conjugated NPs prolonged the plasma level of 5-FU and assisted in the selective accumulation of 5-FU in the liver (vs. other organs spleen, kidney, lungs, and heart) compared to unconjugated one and plain drug. In vivo, bio-distribution, and plasma profile studies resulted in a significantly higher concentration of 5-Fluorouracil liver, suggesting that these carriers are efficient, viable, and targeted carrier of 5-FU treatment of liver cancer.

Degradation-Induced Actuation in Oxidation-Responsive Liquid Crystal Elastomers.

Stimuli-responsive materials that exhibit a mechanical response to specific biological conditions are of considerable interest for responsive, implantable medical devices. Herein, we report the synthesis, processing and characterization of oxidation-responsive liquid crystal elastomers that demonstrate programmable shape changes in response to reactive oxygen species. Direct ink writing (DIW) is used to fabricate Liquid Crystal Elastomers (LCEs) with programmed molecular orientation and anisotropic mechanical properties. LCE structures were immersed in different media (oxidative, basic and saline) at body temperature to measure in vitro degradation. Oxidation-sensitive hydrophobic thioether linkages transition to hydrophilic sulfoxide and sulfone groups. The introduction of these polar moieties brings about anisotropic swelling of the polymer network in an aqueous environment, inducing complex shape changes. 3D-printed uniaxial strips exhibit 8% contraction along the nematic director and 16% orthogonal expansion in oxidative media, while printed LCEs azimuthally deform into cones 19 times their original thickness. Ultimately, these LCEs degrade completely. In contrast, LCEs subjected to basic and saline solutions showed no apparent response. These oxidation-responsive LCEs with programmable shape changes may enable a wide range of applications in target specific drug delivery systems and other diagnostic and therapeutic tools.

Microsponges: A Promising Novel Drug Delivery System

Microsponge is recent novel technique for control release and target specific drug delivery system. More and more developments in drug delivery systems are being integrated to optimize the efficacy and cost-effectiveness of the therapy. Microsponges are polymeric delivery system containing porous microspheres having a size range from 5 to 300µm. Microsponge Delivery System (MDS) is a unique technology for controlled drug delivery. This review article mainly deals with Microsponge drug delivery along with its method of preparation, characterization, advantages and release mechanism of MDS. Microsponges are characterized by particle size, entrapment efficacy, true density, % drug content and % yield, dissolution studies, Resiliency, compatibility studies and in-vitro studies. Wide range of applications is also preferred to develop drug with enhanced safety and efficacy.
 Keywords: Microsponge, Porous microspheres, Control release, Colon.

Recent trends and advances in microbe-based drug delivery systems.

Since more than a decade, pharmaceutical researchers endeavor to develop an effective, safe and target-specific drug delivery system to potentiate the therapeutic actions and reduce the side effects. The conventional drug delivery systems (DDSs) show the improvement in the lifestyle of the patients suffering from non-communicable diseases, autoimmune diseases but sometimes, drug resistance developed during the treatment is a major concern for clinicians to find an alternative and more advanced transport systems. Advancements in drug delivery facilitate the development of active carrier for targeted action with improved pharmacokinetic behavior. This review article focuses on microbe-based drug delivery systems to provide safe, non-toxic, site-specific targeted action with lesser side effects. Pharmaceutical researchers play a vital part in microbe-based drug delivery systems as a therapeutic agent and carrier. The properties of microorganisms like self-propulsion, in-situ production of therapeutics, penetration into the tumor cells, increase in immunity, etc. are of interest for development of highly effective delivery carrier. Lactococcus lactis is therapeutically helpful in Inflammatory Bowel Disease (IBD) and is under investigation of phase I clinical trial. Moreover, bacteria, anti-cancer oncolytic viruses, viral vectors (gene therapy) and viral immunotherapy are the attractive areas of biotechnological research. Virus acts as a distinctive candidate for imaging of tumor and accumulation of active in tumor. Graphical abstract Classification of microbe-based drug delivery system.

Chitosan nanopolymers: An overview of drug delivery against cancer.

Cancer is becoming a major reason for death troll worldwide due to the difficulty in finding an efficient, cost effective and target specific method of treatment or diagnosis. The variety of cancer therapy used in the present scenario have painful side effects, low effectiveness and high cost, which are some major drawbacks of the available therapies. Apart from the conventional cancer therapy, nanotechnology has grown extremely towards treating cancer. Nanotechnology is a promising area of science focusing on developing target specific drug delivery system for carrying small or large active molecules to diagnose and treat cancer cells. In the field of nanoscience, Chitosan nanopolymers (ChNPs) are been emerging as a potential carrier due to their biodegradability and biocompatibility. The easy modification and versatility in administration route of ChNPs has attracted attention of researchers towards loading chemicals, proteins and gene drugs for target specific therapy of cancer cells. Therefore, the present review deals with the growing concern towards cancer therapy, introduction of ChNPs, mode of action and other strategies employed by researchers till date towards cancer treatment and diagnosis ChNPs.

Noisomes: as novel vesicular drug delivery system

Target-specific drug-delivery systems for the administration of pharmaceutical compounds enable the localization of drugs to target sites within the body. The basic component of drug delivery systems is an appropriate carrier that protects the drug from rapid degradation or clearance and thereby enhances drug concentration in target tissues. Niosome are microscopic non-ionic surfactant bilayer vesicles obtained on hydration of synthetic nonionic surfactants, with or without incorporation of cholesterol or their lipids. The amphiphilic nature of niosomes promotes their efficiency in encapsulating lipophilic or hydrophilic drugs. Noisome are promising vehicle for drug delivery and being non-ionic, more stable, inexpensive, biodegradable, biocompatible, non immunogenic and exhibit flexibility in their structural characterization. Various additives in niosomes include nonionic surfactant as film forming agent, cholesterol as stabilizing and rigidizing agent for the bilayer and various charge inducers which develop a charge on the surface of niosomes and stabilize the prepared formulation by the resulting repulsive forces. Niosomes have been widely evaluated for controlled release and targeted delivery for the treatment of cancer, viral infections, microbial diseases, psoriasis, leishmaniasis, migraine, parkinson and other diseases. Niosomes can prolong the circulation of the entrapped drug in body. Encapsulation of drug in vesicular system can be predicted to prolong the existence of drug in the systemic circulation and enhance penetration into target tissue, perhaps reduce toxicity if selective uptake can be achieved. In addition to conventional, oral and parenteral routes, they are amenable to be delivered by ocular, transdermal, vaginal and inhalation routes. Delivery of biotechnological products including vaccine delivery with niosomes is also an interesting and promising research area. More concerted research efforts, however, are still required to realize the full potential of these novel systems. This review article focuses on the concept of niosomes, advantages and disadvantages, composition, method of preparation, separation of unentrapped drug, factors influencing the niosomal formulation and characterization, marketed formulations of niosomes and also gives up to date information regarding recent applications of niosomes in drug delivery.
 Keyword: Drug-delivery system, Niosomes,

Chitosan-coated doxorubicin nano-particles drug delivery system inhibits cell growth of liver cancer via p53/PRC1 pathway

BackgroundNano-particles have been widely used in target-specific drug delivery system and showed advantages in cancers treatment. This study aims to evaluate the effect of chitosan coated doxorubicin nano-particles drug delivery system in liver cancer. MethodsThe chitosan nano-particles were prepared by using the ionic gelation method. The characterizations of the nano-particles were determined by transmission electron microscopy. The cytotoxicity was detected by MTT assay, and the endocytosis, cell apoptosis and cell cycle were examined by flow cytometry. The protein level was analyzed with western blot. The dual luciferase reporter assay was performed to assess the interaction between p53 and the promoter of PRC1, and chromatin immune-precipitation was used to verify the binding between them. ResultsThe FA-CS-DOX nano-particles were irregular and spherical particles around 30–40 nm, with uniform size and no adhesion. No significant difference was noted in doxorubicin release rate between CS-DOX and FA-CS-DOX. FA-CS-DOX nano-particles showed stronger cytotoxicity than CS-DOX. FA-CS-DOX nano-particles promoted the apoptosis and arrested cell cycle at G2/M phase, and they up-regulated p53. FA-CS-DOX nano-particles inhibited cell survival through p53/PRC1 pathway. ConclusionChitosan-coated doxorubicin nano-particles drug delivery system inhibits cell growth of liver cancer by promoting apoptosis and arresting cell cycle at G2/M phase through p53/PRC1 pathway.

Modeling and simulation of the electro-chemical behavior of chemically stimulated polyelectrolyte hydrogel layer composites

Polyelectrolyte hydrogels are viscoelastic electroactive polymers which respond to external physical or chemical stimuli by a reversible volume phase transition. Novel fabrication methods allow the creation of hydrogel layer composites in which each layer shows a different sensitivity (e.g. to a different stimulus). This offers new opportunities, for example, in the design of new microsensors, microactuators and microfluidic devices as well as for high-selective membranes and target-specific drug delivery systems. Since only few research groups numerically investigated the transport mechanisms in hydrogel layer composites, a gap remains to describe the movement and transient distribution of ions inside the layer system. In this article, the multifield formulation is adopted to describe the transient distribution of ions in salt-sensitive hydrogel layer composites on the basis of a numerical simulation. For this, the Nernst-Planck and the Poisson equation are solved using one-dimensional finite elements for both anionic-anionic and anionic-cationic gel layer composites under chemical stimulation. Between adjacent gels, an additional interlayer is introduced to account for the physical and chemical bonding region between the gels. Adaptive mesh refinement provides a good resolution close to the interface between the adjacent gel layers. The obtained results are used to predict the osmotic pressure inside the gels and the dependent swelling of the gel layer composite. The excellent agreement of the obtained results with the Donnan equilibrium demonstrates the high potential of the method applied to predict the behavior of hydrogel layer composites.

Porphyrin encapsulated poly(3- hydroxybutyrate) microspheres in target specific photodynamic therapy for cancer

Event Abstract Back to Event Porphyrin encapsulated poly(3- hydroxybutyrate) microspheres in target specific photodynamic therapy for cancer Hima Puthussery1, Ipsita Roy1, Anatoily Markiv1, Eugen Stulz2, Pooja Basnett1 and Peter Thomas1 1 University Of Westminster, Faculty of science and technology, United Kingdom 2 University of Southampton, Department of Chemistry, United Kingdom Introduction: Photodynamic therapy (PDT) is an emerging alternative treatment modality to conventional cancer therapies. This involves the application of photosensitive drugs, systemically or tropically, followed by illumination with light of a suitable wavelength and dosage. A drug delivery system that is biodegradable, biocompatible, non-immunogenic and capable of encapsulation without altering the properties of the photosensitizer is desired. Biosynthetic polyhydroxyalkanoates (PHAs) have been extensively researched within the context of drug delivery [1]. This research investigates Poly(3-hydroxybutyrate) (P(3-HB)) microspheres as suitable target specific drug delivery systems of Porphyrin derivatives (protoporphyrin IX, tetraphenylporphyrin and hematoporphyrin ether) on mammary cancer cells. The microspheres have been coupled with anti-HER2 to enable target specificity for better incorporation by SK-BR-3 cells that overexpress HER-2 marker. Materials and Methods: Production of photosensitizer encapsulated microsphere using P(3HB): P(3HB) synthesised using Kannan- Rehaceck media [2] was used for producing microspheres by solid-in-oil-in-water emulsion method. Varying process parameters were tested based on experiment design generated by design expert software; 2.5%w, 5%w and 10%w of drugs were then encapsulated in the P(3HB) microspheres. Surface adsorption of the anti HER-2 antibody on microspheres: RFP coupled anti HER-2 antibody was expressed in Rosetta gami B(DE3) E. coli. These His-tagged proteins were purified using immobilised metal affinity chromatography and linked to the photosensitizer-encapsulated microspheres using surface adsorption. Protein adsorbed was quantified using Bradford’s assay. Photoexcitaion and cytotoxicity tests: SK-BR-3 was cultured as specified by ATCC and incubated with the microspheres for 48 hours and subjected to white light exposure for 30 minutes. MTT assay was performed to assess cytotoxicity and live/dead staining was performed for confocal imaging. Results and Discussion: Without photoexcitation, microspheres loaded and not loaded with porphyrin derivatives have similar cytotoxicity. Cytotoxic effect increased with increasing drug loading in each case and was found to be the highest in case of tetraphenylporphyrin (Figure 1). anti HER-2 conjugation seemed to cause a further increase in cytotoxity in the case of hematoporphyrin ether and tetraphenylporphyrin, which was statistically significant (p<0.05). The absence of increased cytotoxicity in the case of protoporphyrin IX is attributed to loss of activity presented by processing conditions and is to be further investigated. The life span of singlet oxygen species generated is only ~3.5micro seconds and apoptotic factors generated by these have diffusion range of only 0.01-0.02micro meters [3]. Hence, successful localisation of the photosensitizer in the target is a key factor in determining the extent of photodynamic reaction caused. A further addition of a target specific antibody such as anti- HER2 recognizing the antigens presented by neoplastic transformation will result in a more efficient Photoimmunotargeting (PIT) [3]. The cells treated with these microspheres seemed to have much become enlarged (~60mm) as opposed to the others, suggesting a possible phagocytic mechanism (Figure 2). Conclusion: Biosynthetic P(3-HB) is an excellent choice for synthesizing porous microspheres for photosensitizer delivery. Of the three porphyrin derivatives compared, tetraphenylporphyrin was found to be the most cytotoxic. As anti- HER2 conjugated microspheres were found to exhibit increased cytotoxicity, it can be concluded that these are promising candidates in Photoimmunotargeting. I would like to thank Cavendish scholarship, University of Westminster.

Tailored Doxorubicin‐Hyaluronan Conjugate as a Potent Anticancer Glyco‐Drug: An Alternative to Prodrug Approach

Releasibility of doxorubicin from drug-conjugates is believed to be a prerequisite for its anti-cancer activity. Here, a new glyco-drug approach that circumvents the releasibility restriction is reported, opening a new possibility to design efficient, target specific drug delivery system. It is discovered that stable amide coupling of doxorubicin (DOX) tohyaluronan (HA) shows dose dependent cytotoxicity to CD44 positive human coloncancer cells (HCT116) as compared to human breast cancer cells(MCF-7) and mouse fibroblast cells (NIH-3T3), which express less CD44 receptor. This direct conjugation approach is an easy scalable strategy that could be adopted to design innocuous anti-tumor nanoparticle formulations.