MRC/DBT Workshop UK-India Centre for Advanced Technologies-Minimising the indiscriminate use of Antibiotics (UKICAT–MA) 14th/15th March 2016, Hyderabad, India.

yesOn 14/15th March 2016 we held a MRC/DBT funded workshop on the theme of Materials to Combat Antibiotic Resistance. The workshop was part of a continuing series of events that are part of the work of UK-India Centre for Advanced Technologies-Minimising the indiscriminate use of Antibiotics (UKICAT–MA). The following is the collection of presentations and the results of discussions highlighting key themes for future work by this group. Combating antibiotic resistance is perhaps the biggest issue facing the global community in the 21st century and no other area, with the exception perhaps of nuclear conflict, has the capacity to significantly reduce living standards and mortality rates. Key objectives identified by WHO1 in this area among five key aspects, include: Objective 4-to optimize the use of antimicrobial agents Objective 5-new medicines, diagnostic tools, vaccines and other interventions Our aims in this series of workshops are to provide an Indo-UK forum for: discussions of our advances in providing technologies to address these objectives; facilitate the interface between UK and Indian clinicians, materials and biological scientists and to identify key areas for new projects. An important aspect of the work in a global context is that by combining the UK and Indian community and clinical experiences we cover most of the scenarios that the global population might expect to encounte

Co-delivery of curcumin and STAT3 siRNA using deformable cationic liposomes to treat skin cancer

<p>Skin cancer is one of the most widely prevalent cancer types with over expression of multiple oncogenic signaling molecules including STAT3. Curcumin is a natural compound with effective anti-cancer properties. The objective of this work was to investigate the liposomal co-delivery of curcumin and STAT3 siRNA by non-invasive topical iontophoretic application to treat skin cancer. Curcumin was encapsulated in cationic liposomes and then complexed with STAT3 siRNA. The liposomal nanocomplex was characterized for particle size, zeta-potential, drug release and stability. Human epidermoid (A431) cancer cells were used to study the cell uptake, growth inhibition and apoptosis induction of curcumin-loaded liposome–siRNA complex. Topical iontophoresis was applied to study the skin penetration of nanocomplex in excised porcine skin model. Results showed that curcumin-loaded liposome–siRNA complex was rapidly taken up by cells preferentially through clathrin-mediated endocytosis pathway. The co-delivery of curcumin and STAT3 siRNA using liposomes resulted in significantly (<i>p</i> < .05) greater cancer cell growth inhibition and apoptosis events compared with neat curcumin and free STAT3 siRNA treatment. Furthermore, topical iontophoresis application enhanced skin penetration of nanocomplex to penetrate viable epidermis. In conclusion, cationic liposomal system can be developed for non-invasive iontophoretic co-delivery of curcumin and siRNA to treat skin cancer.</p

Liposomal hydrogel formulation for transdermal delivery of pirfenidone

<p><i>Context</i>: Pirfenidone (PFD) is an anti-fibrotic and anti-inflammatory agent indicated for the treatment of idiopathic pulmonary fibrosis (IPF). The current oral administration of PFD has several limitations including first pass metabolism and gastrointestinal irritation.</p> <p><i>Objective</i>: The aim of this study is to investigate the feasibility of transdermal delivery of PFD using liposomal carrier system.</p> <p><i>Materials and methods</i>: PFD-loaded liposomes were prepared using soy phosphatidylcholine (SPC) and sodium cholate (SC). Encapsulation efficiency (EE) of PFD in liposomes was optimized using different preparation techniques including thin film hydration (TFH) method, direct injection method (DIM) and drug encapsulation using freeze–thaw cycles. <i>In vitro</i> drug release study was performed using dialysis membrane method. The skin permeation studies were performed using excised porcine ear skin model in a Franz diffusion cell apparatus.</p> <p><i>Results and discussion</i>: The average particle size and zeta-potential of liposomes were 191 ± 4.1 nm and −40.4 ± 4.5 mV, respectively. The liposomes prepared by TFH followed by 10 freeze–thaw cycles showed the greatest EE of 22.7 ± 0.63%. The optimized liposome formulation was incorporated in hydroxypropyl methyl cellulose (HPMC) hydrogel containing different permeation enhancers including oleic acid (OA), isopropyl myristate (IPM) and propylene glycol (PG). PFD-loaded liposomes incorporated in hydrogel containing OA and IPM showed the greatest flux of 10.9 ± 1.04 μg/cm²/h across skin, which was 5-fold greater compared with free PFD. The cumulative amount of PFD permeated was 344 ± 28.8 μg/cm² with a lag time of 2.3 ± 1.3 h.</p> <p><i>Conclusion</i>: The hydrogel formulation containing PFD-loaded liposomes can be developed as a potential transdermal delivery system.</p

Zein Microneedles for Transcutaneous Vaccine Delivery: Fabrication, Characterization, and in Vivo Evaluation Using Ovalbumin as the Model Antigen

Transcutaneous antigen administration provides an alternative to invasive syringe injections. The objective of this study was to investigate the feasibility of fabrication and antigen delivery using microneedles made from corn protein, zein. Micromolding technique was used to cast cone-shaped zein microneedles (ZMNs). The insertion of ZMNs and the delivery of the model antigen, ovalbumin (OVA), into the skin was confirmed by histological examination and confocal microscopy. In addition, a significantly (<i>p</i> < 0.05) lower bacterial skin penetration was observed after ZMN application compared with hypodermic syringe application. OVA coated on ZMNs was stable after storage under ambient and refrigerator conditions. Transcutaneous immunization studies showed significantly (<i>p</i> < 0.001) greater antibody titers (total IgG, IgG1, and IgG2a) after the application of OVA-coated ZMNs and OVA intradermal injection compared with the control group. Taken together, antigen-coated ZMNs can be developed for transcutaneous vaccine delivery

Layer-by-Layer Polymer Coated Gold Nanoparticles for Topical Delivery of Imatinib Mesylate To Treat Melanoma

The aim of this study was to investigate the feasibility of using layer-by-layer polymer coated gold nanoparticles (AuNP) as a carrier for topical iontophoretic delivery of imatinib mesylate (IM). AuNP were prepared by the Turkevich method and were stabilized and functionalized using polyvinylpyrrolidone and polyethylene imine. The functionalized AuNP were then sequentially coated with anionic poly­(styrenesulfonate) and cationic polyethylene imine and loaded with IM. The layer-by-layer polymer coated AuNP (LbL-AuNP) showed average particle size and zeta-potential of 98.5 ± 4.3 nm and 32.3 ± 1.3 mV respectively. After LbL coating of AuNP, the surface plasmon resonance wavelength shifted from 518 to 530 nm. The loading efficiency of IM in LbL-AuNP was found to be 28.3 ± 2.3%, which was greatest for any small molecule loaded in AuNP. <i>In vitro</i> skin penetration studies in excised porcine ear skin showed that iontophoresis (0.47 mA/cm²) application enhanced the skin penetration of IM loaded AuNP by 6.2-fold compared to passive application. Tape stripping studies showed that iontophoresis of IM loaded LbL-AuNP retained 7.8- and 4.9-fold greater IM in stratum corneum and viable skin respectively compared with iontophoresis of free IM. LbL-AuNP were taken up rapidly (15 min) by B16F10 murine melanoma cells. Furthermore, IM loaded LbL-AuNP significantly (<i>p</i> < 0.001) decreased B16F10 cell viability compared to free IM. We have shown for the first time that IM can be delivered by topical application using LbL coated gold nanoparticles to treat melanoma