6th International Conference on
Drug Delivery and Formulations

Biography:

Dr. Thomas J. Webster’s (H index: 109; Google Scholar) degrees are in chemical engineering from the University of Pittsburgh (B.S., 1995; USA) and in biomedical engineering from RPI (Ph.D., 2000; USA). He has served as a professor at Purdue (2000-2005), Brown (2005-2012), and Northeastern (2012-2021; serving as Chemical Engineering Department Chair from 2012 - 2019) Universities and has formed over a dozen companies who have numerous FDA approved medical products currently improving human health.  He has graduated over 200 Ph.D. students and has over 800 publications. Dr. Webster has numerous awards including: 2020, World Top 2% Scientist by Citations (PLOS); 2020, SCOPUS Highly Cited Research (Top 1% Materials Science and Mixed Fields); 2021, Clarivate Top 0.1% Most Influential Researchers (Pharmacology and Toxicology), and is a fellow of over 8 academic societies.

Abstract:

Introduction: Over the past 20 years, the use of nanotechnology in medicine has grown from the unknown to now significantly helping to prevent, diagnosis, and treat numerous diseases. This includes the use of nano biodegradable metals (like Mg) and self-assembled materials that carry metals and are biodegradable. Methods: Numerous biodegradable metal nanoparticles as well as nanotextures have been synthesized¹.  For example, Mg nanoparticles were pressed into model surfaces and soaked in NaOH to create a nanoscale surface roughness. Similarly, self-assembled materials containing biodegradable metals have been synthesized using standard organic chemistry methods (Figure 1)². All materials have been studied for their ability to attach to viruses (such as SARS-CoV-2) to keep the virus from replicating. Further, such materials have been used to fight infection, inhibit cancer cell growth, and improve tissue growth using standard in vivo and in vitro methods^{3, 4}. Results: For the self-assembled nanomaterials, one type of self-assembled nanomaterial composed of DNA base pairs has been the focus of our efforts to functionalize with specific peptides suitable for attaching to SARS-CoV-2 and all of its known variants. After binding to SARS-CoV-2, the self-assembled molecule inhibits SARS-CoV-2 binding to and entering mammalian cells keeping it from replicating. Moreover, these unique self-assembled nanomaterials have been functionalized with peptides to attach to and penetrate to kill gram-positive bacteria, gram-negative bacteria, and antibiotic-resistant bacteria. Further, these self-assembled nanomaterials were functionalized with peptides to attach to and kill cancer cells. Lastly, significant effort has been spent to functionalize these self-assembled nanomaterials with peptides to promote bone, cartilage, vascular, skin and other tissue growth. Conclusions: In vitro and in vivo studies will be presented as well as lessons learned trying to commercialize university-based research into real commercial products.

Biography:

Nanoparticle development and imaging for end user applications such as therapeutics and diagnostics. Nanomaterial development for therapeutics encompass antibacterial agent conjugated material which enhance the the efficacy of the antibacterial agent. Diagnostics include nanoparticle based fluorescent imaging of surface lectin receptors on lung human carcinoma cell lines.
Discriminant analysis based pattern recognition to recognize patterns of lectin and carbohydrate binding.

Abstract:

The work demonstrates the use of carbohydrate-conjugated nanomaterial (glyconanomaterial) to target bacterial pathogens. A collection of systematic studies done by several groups has demonstrated that bacteria can be specifically targeted using various oligosaccharides. Through our preliminary investigations we have discovered that oligosaccharide conjugated nanoparticles (glyconanoparticles) could be used to target strain specific bacteria. For example D-maltoheptaose (G7) and trehalose conjugated nanoparticle used to effectively target Escherichia coli and Mycobacterium spp. Antibiotic resistance in pathogenic bacterial strains is a growing global concern. We have demonstrated that these glyconanoparticles have been used as a carrier for antibiotics that would help target bacteria and reduce minimum inhibitory concentration of a conventional antibiotic. Antibiotic streptomycin (Str) is a broad range aminoglycoside typically used in the treatment of tuberculosis. We have bi-functionalized a nanoparticle using carbohydrate-G7 antibiotic-Str to produce glyconanoantibiotics (GNAs). As proof of concept for active targeting GNAs are used against a highly Str resistant E. coli strain. The GNAs demonstrated size dependent increased antibacterial efficacy few log folds improvement over the free the free antibiotic (Str).

Biography:

Panpan Ma has been a PhD student in the Faculty of Health (Université Paris Cité) since 2019 under the supervision of Dr. Yohann Corvis. She focuses on the preparation of anti-cancer and anti-inflammatory nanocrystal suspensions by using a solvent/antisolvent precipitation approach. The original nanocrystals prepared present targeting and sustained release properties, modifying the therapeutic impact of the drug. Her work includes synthesis of nanocrystals, structural characterization, dissolution studies, in vitro and in vivo studies, emphasizing the advantages of innovative drug delivery systems.

Abstract:

Up to 90% of the active pharmaceutical ingredients (API) currently in development present low solubility because approximately 65% and 15% belong to Class II and Class IV of the biopharmaceutical classification system (BCS), respectively. 1 Therefore, in order to develop new drugs towards clinical applications, improving API solubility is a major challenge for the pharmaceutical field. Crystal nanosuspensions, otherwise known as nanocrystals (NCs), consisting of pure API stabilized by a surface-active agent, have emerged as one of the most promising approaches for overcoming bioavailability issues. This allows optimizing the therapeutic efficiency of the NC drugs with better safety and targeting properties, while being administrated through various routes.2,3 The UTCBS lab pioneered the bottom-up approach with minimal amount of Pluronic®F-127 as stabilizer to engineer etoposide (BCS class IV) NCs for anti-cancer treatment, which strengthened the feasibility of drug NCs as effective delivery systems for nanomedicines administered parenterally and with lower side effects than the related marketed product, Toposar®. 4 Interestingly, around 40 NC drug formulations are in market and under clinical trials, but only two marketed antiinflammatory products have been approved by the U.S. Food and Drug Administration (i.e. Naprelan® and Acticoat®, approved in 2006 and 2008, respectively), and another one, the anti-inflammatory drug Paxceed®, is currently on phase III of clinical trial. 5 The present work consists of developing our expertise on anti-cancer therapeutic NCs with other API pharmaceutical classes like anti-inflammatory with curcumin (BCS class IV), a typical natural compound extracted from turmeric， and prednisolone (non-classified BCS class), a synthetic cortisol compound. For that purpose, two different Pluronic®derivatives, namely Pluronic® F-127 and F-68 were evaluated. By optimizing several experimental parameters, the API/stabilizing agent ratio were adjusted to screen out the best formulation of nanocrystal with convenient yield, high stability, sustained release performance and improved therapeutic activity.

Biography:

Abstract:

The objective of the present investigation was formulate & characterize the microsponge of Mefenamic acid, these microsponges were prepared by quassi-emulsion method. Pre formulation studies by FTIR, revealed no interaction between pure drug and the different polymers used. The prepared microsponges were characterized for their production yield, drug content, mean particle size & entrapment efficiency, Effect of formulation variables was also studied. The microsponge containing 0.5 gm of poly vinyl alcohol, 0.6 gm of ethyl cellulose and 5ml ethanol was found to be good compared to the other formulations prepared. The best microsponges (M3, M6, and M9) were in cooperated into gel and emulgel. The topical gel and emulgel formulation were evaluated for their organoleptic characters, viscosity, spreadability, drug content and drug release studies. The results showed microsponge gel of mefenamic acid containing eudragit RS100 microsponge emulgel of mefenamic acid containing ethyl cellulose as best formulations, the in vitro drug release profile of mefenamic acid was found to better from the emulgel formulation compared to gel formulation.

Biography:

Abstract:

Statement of the Problem: Cancer is a world-wide problem. Better diagnostic technologies can improve cancer detection and outcomes from cancer treatments. Advanced diagnostic technologies such as nano delivery system serve as means of diagnostic tools or to deliver therapeutic agents (chemotherapeutic agents, biological agents, immunotherapeutic agents etc.) site-specific, and target-oriented delivery of precise medicines in a controlled manner. Methodology & Theoretical Orientation: The therapeutic progress of cell-based therapies was assessed by labelling chimeric antigen receptor (CAR) T-cells with novel radioactive labelled superparamagnetic iron oxide nanoparticle and tracked using clinical hybrid imaging modalities. Findings: The cell tracking platform in first-in-human studies provided real-time data on distribution, migration and localization of CAR-T cells. It further provided insight into physiology, efficacy and toxicities of cell based therapy. The dual imaging technology developed is simple, scalable, non-invasive and biocompatible and addressed the lack of effective imaging tools for cell-based therapies. It is not only suitable for early tumour detection but also for ongoing monitoring in oncology. In another study, a sustainable, reagent-less and one-pot ultrasonic methodology has been developed to transform natural biomaterials into micro/nanocrystals with distinct morphologies which then can be used to load anticancer drugs with high loading efficiency) for site specific and targeted delivery in controlled manner. The synthesized particles showed, high thermostability, antioxidant properties and a remarkable antiproliferative effect in human breast cancer cells. Conclusion & Significance: Nanomedicine has revolutionized the way we discover, image and administer drugs in biological systems. The first study validated and demonstrated the potential for cell tracking in immunotherapy. The second study emphasized on green chemistry to convert novel natural biomaterials into nano drug delivery system for precision medicine. 

Biography:

A committed researcher experience in nanoparticles for drug delivery targeting and performing tissue culture, synthesis of nanoparticles, cytotoxicity, apoptosis, migration, molecular evolution of cancer, and other assays, responsible for the synthesis of nanoparticles in different shapes and conjugation with different ligands, and characterized GNPs of various shapes, then functionalized GNPs with various ligands, assessing chemical and colloidal stability, to create a Nano-platform for cancer treatment as targeting drug delivery system for chemotherapeutic agents. finally evaluating cytotoxicity and anti-invasion properties

Abstract:

Prostate cancer is one of the most common cancers in men. Cell invasion is an important step in the process of cancer metastasis. Herein, gold nanorods (GNRs) and polyethylene glycol (PEG)- coated GNRs were conjugated with polydopamine (PDA). The PDA-nanoconjugates demonstrated excellent colloidal stability upon lyophilization and dispersion in cell culture media with or without the addition of fetal bovine albumin (FBS), compared to unconjugated GNRs. PDA-nanoconjugates exhibited a considerable cytotoxicity against DU-145 and PC3 prostate cancer cell lines over a concentration range of 48 μg/mL–12 μg/mL, while they were biocompatible over a concentration range of 3.0 μg/mL–0.185 μg/mL. Furthermore, PDA-nanoconjugates demonstrated possible anti- invasion activity towards prostate cancer cell lines, particularly DU-145 cell line, by reducing cell migration and cell adhesion properties. The PDA-nanoconjugates could be considered a promising nano-platform toward cancer treatment by reducing the invasion activity; it could also be considered a drug delivery system for chemotherapeutic agents

Biography:

Himanshu Verma completed her M.Pharm degree in Pharmaceutical Chemistry from the Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, India. She is currently pursuing a Ph.D. in the same department under the supervision of Dr.Om Silakari. She is a senior research fellow in the ICMR fellowship project and works, by using in silico techniques, on designing heterocycles for addressing the problem of resistant cancer

Abstract:

Aldehyde dehydrogenase 1 (ALDH1A1), an oxidoreductase class of enzymes, is overexpressed in various types of cancer cell lines and is the major cause of resistance to the Food and Drug Administration (FDA)‐approved drug, cyclophosphamide (CP). In cancer conditions, CP undergoes a sequence of biotransformations to form an active metabolite, aldophosphamide, which further biotransforms to its putative cytotoxic metabolite, phosphoramide mustard. However, in resistant cancer conditions, aldophosphamide is converted into its inactive metabolite, carboxyphosphamide, via oxidation with ALDH1A1. Herein, to address the issue of ALDH1A1 mediated CP resistance, we report a series of benzo[d]oxazol‐2(3H)‐one and 2‐oxazolo[4,5‐b]pyridin‐2(3H)‐one derivatives as selective ALDH1A1 inhibitors. These inhibitors were designed using a validated 3D‐quantitative structure activity relationship (3D‐ QSAR) model coupled with scaffold hopping. The 3D‐QSAR model was developed using reported indole‐2,3‐diones based ALDH1A1 inhibitors, which provided field points in terms of electrostatic, van der Waals and hydrophobic potentials required for selectively inhibiting ALDH1A1. The most selective indole‐ 2,3‐diones‐based compound, that is, cmp 3, was further considered for scaffold hopping. Two top‐ranked bioisosteres, that is, benzo[d]oxazol‐2(3H)‐one and 2‐oxazolo[4,5‐b]pyridin‐ 2(3H)‐one, were selected for designing new inhibitors by considering the field pattern of 3D‐QSAR. All designed molecules were mapped perfectly on the 3D‐QSAR model and found to be predictive with good inhibitory potency (pIC50 range: 7.5–6.8). Molecular docking was carried out for each designed molecule to identify key interactions that are required for ALDH1A1 inhibition and to authenticate the 3D‐QSAR result. The top five inhibitor‐ALDH1A1 complexes were also submitted for molecular dynamics simulations to access their stability. In vitro enzyme assays of 21 compounds suggested that these compounds are selective toward ALDH1A1 over the other two isoforms, that is, ALDH2 and ALDH3A1. All the compounds were found to be at least three and two times more selective toward ALDH1A1 over ALDH2 and ALDH3A1, respectively. All the compounds showed an IC50  value in the range of 0.02–0.80 μM, which indicates the potential for these to be developed as adjuvant therapy for CP resistance.

Biography:

Abstract:

In drug delivery, solid dosage forms, of which tablet is the commonest, are still the leading preferences. An area of research focus in tablet drug delivery is the search for tablet excipients. This study was aimed at evaluating and optimizing native Taro Boloso-I starch as a tablet disintegrant. Methods: The response surface methods with central composite design (CCD-RSM) was used for the analysis and optimization of the concentration of native Taro Boloso-I starch and compression force. Wet granulation method was used for the preparation of paracetamol tablets. The response variables considered were tablet crushing strength, friability and disintegration time. Results and Discussions: Both the native Taro Boloso-I starch concentration and compression force had increasing effect on the tablet breaking force. The friability of the tablets was shown to decrease with increasing levels of the disintegrant concentration. On the other hand, compression force had a decreasing effect on friability in the investigated range. The disintegration time of the tablets was found to decrease with the concentration of the starch. The paracetamol tablets prepared with the optimized levels of native Taro Boloso-I starch and compression force showed tablet breaking force of 116.24 N, friability of 0.153%, disintegration time of 1.36 min, disintegration efficiency ratio of 562.3 N /(%Min) and comparative disintegration efficiency ratio 13.6 with respect to commercial potato starch. Conclusions: The tablets exhibited improved crushing strength, friability, in vitro disintegration time and disintegration efficiency ratio which suggest the novel applicability of the native Taro Boloso-I starch as an efficient pharmaceutical tablet disintegrant.

Biography:

Dr. Vijay Kulkarni (M.Pharm, Ph.D) has experience in pharmaceutical industry working on solid oral dosage forms development especially using hot melt extrusion or Twin screw processing for Solubility enhancement of poorly soluble drugs and for continuous Twin Screw Granulation. He has developed various formulations using this technology and transferred the technology to various pharmaceutical industries. He is also a recipient of Rising Star Award in Formulation Development, presented during FDD 2019 Conclave, Hyderabad.  He has 15 years of research experience in pharmaceutical industry and academic research as formulation development scientist. He was a Post-Doctoral research fellow at University of Mississippi, USA working with Prof. Michael Repka

Abstract:

Statement of the Problem:

Pharmaceutical industry has faced increasing pressure to reduce costs due to the competition raised from generics production [1]. This has induced a shift from batch to continuous manufacturing because of several advantages (reduction in development and processing time, equipment size, manufacturing space, costs, quality control and less scale-up problems, increased control and ability to integrate process analytical tools) and due to this there are several initiatives are undertaken by regulatory agencies and pharmaceutical companies [2]. Continuous granulation using twin screw granulation (TSG) has emerged as an alternative to conventional batch granulation [3 & 4] and this is discussed in this presentation with case studies.

Methodology & Theoretical Orientation:

The continuous granulation sequence starts with 1) feeding the material (API+ excipient/s) through feeder (Gravimetric or Volumetric) in the twin screw processor as a premix blend or feeding the individual materials to continuous blender and then to the Twin screw processor, 2) addition of water or binder solution into the processor through pump, 3) mixing or kneading of the powder blend with water or binder solution by the specific configuration of screw elements, 4) drying and sizing inside the processor or through the integrated dryer and mill as shown in Fig 1. The granules and resultant tablets were evaluated for physical-chemical properties.

Biography:

Dr. Pavitra has his expertise in pharmaceutical nanotechnology and drug evaluation in improving the women health and wellbeing. His pharmacodynamic and pharmacokinetic evaluation model based on osteoporotic wistar rats for improving osteoporotic related disorders is commendable. He has gained this after years of experience in animal model research, drug evaluation, teaching and administration both in research and educational institutions. He has published more than 20 research papers and received national as well as international awards in drug delivery and nanotechnological based research

Abstract:

Statement of the Problem: Osteoporosis emerged as a chronic disease of skeleton system leading to weaken bones and hip fractures making it a burden to the society. During lifetime, one out of every three women and one out of every six males will experience an osteoporotic fracture. Every minute, eight new fracture cases are reported in the EU. In the European Union, it is projected that over 23 million men and women are at high risk of osteoporotic fractures. According to estimates from 2019, osteoporosis and the 4.3 million fragility fractures it generates cost Europe's health-care systems more than €56 billion every year.  Methodology: A nano complex tagged pamidronate was prepared with hot-micro-emulsification and ultrasonication method. The prepared formulation was characterized for particle size, zeta potential, in-vitro drug release, ex-vivo gut permeation and in-vivo anti osteoporosis activity. Size of nanoformulation was further confirmed by TEM. Bone mineral density of wistar rat femur was determined using micro-computed tomography and bone mechanical strength was determined with universal testing machine. Clinical findings: The oral bioavailability and permeability was enhanced by 37.56 % and 152.71% respectively. Bone mineral density was enhanced in female wistar rat models by 25.81 % compared to marketed formulation. Bone strength was enhanced by 19.22 % Conclusion & Significance: Bisphosphonates are the primary therapeutic agents for treating osteoporosis but very low oral bioavailability limits their use. In this paper, a novel approach was utilized to develop orally applicable nanoformulation with significant oral bioavailability to reduce injection and cost burden to the society. This research will be of great interest in further studies with significant outcomes to treat post-menopausal osteoporosis in women.

Biography:

Mr. Gaurav is a nanomedicine researcher who focuses on alopecia and its treatment. He has two years of experience 3D printing tablets and is interested in developing novel Alopecia treatment solutions. He has worked in both hospitals and educational institutions, doing research and evaluating drug and delivery systems. His strategy is unique, and his execution is as effective.

Abstract:

Background: Efficacy of minoxidil for the treatment of androgenetic alopecia has been demonstrated through several clinical studies, however scalp retention and penetration, which is imperative for application frequency, has not been determined till date.

Methods: The scalp retention and penetration of the three radiolabeled minoxidil (5%) formulations: Formulation A (40% alcohol and 60% water); B (30% alcohol, 10% PG and 60% water) and C (40% alcohol, 10% HPC and 60% water) were prepared. Ex vivo retention, penetration and permeation was conducted using swine ear skin and in vivo scalp retention and penetration of the formulations was evaluated in human participants with male pattern baldness using scintigraphy.

Results: Minoxidil radiolabeling efficiency of 99.1% was observed when 0.2% stannous chloride was used as reducing agent at pH 6 and incubation temperature of 40°C. Results showed that formulation C containing 10% HPC demonstrated highest viscosity (0.8 Pa.s) and significantly higher ex vivo retention (p < 0.05) and permeation (0.75±0.12%, 8h) compared to Formulation A (0.40±0.05%, 8h) and B (0.44±0.05%, 8h). In vivo studies using human scalp showed significantly higher (p < 0.05) scalp retention in FC group (57±2.3%) compared to FA (41±1.9%) and FB (44±3.4%) group. Post 8 h application of formulation, scalp penetration in FC group was nearly 2.8-fold and 2.2-fold higher than group FA and FB, respectively. Further, absence of minoxidil in systemic circulation during study duration indicates safety.

Conclusions: In conclusion, increasing the contact time of formulation with scalp by modifying viscosity might result in reduced frequency of application and improved efficacy.