Other Pharmacy and Pharmaceutical Sciences Commons^™

Gadolinium Nanoparticles: Emerging Platforms Beyond Imaging For Drug Delivery And Theranostics, Amir Nasrolahi Shirazi, Rajesh Vadlapatla, Ajoy Koomer, Heyam Zayed, Paris Marabut, Keykavous Parang

Pharmacy Faculty Articles and Research

Gadolinium nanoparticles (GdNPs) have gained increasing attention as multifunctional metal-based nanoplatforms that extend far beyond their traditional use as magnetic resonance imaging (MRI) contrast agents. Their specific magnetic properties, tunable physicochemical features, and tunable biocompatibilities with biocompatible coatings give them great potential as drug delivery and theranostic applications. They offer greater stability, lower systemic toxicity, and more surface modification options compared to molecular gadolinium chelates. The functionalized GdNPs not only show excellent properties as drug carriers for their specific indications but also serve as agents in various imaging modalities with superior therapeutic efficacy by means of radio sensitization and magnetically …

Selenium Nanoparticles As Versatile Delivery Tools, Amir Nasrolahi Shirazi, Rajesh Vadlapatla, Ajoy Koomer, Kyle Yep, Keykavous Parang

Pharmacy Faculty Articles and Research

Selenium nanoparticles (SeNPs) have emerged as promising metal-based nanoparticles for drug delivery due to their unique physicochemical properties, intrinsic bioactivity, and biocompatibility. SeNPs offer a lower toxicity, higher bioavailability, and flexibility to be customized for surface chemistry compared to traditional selenium compounds. Advances in synthetic strategies, including chemical reduction, green biosynthesis, and surface functionalization with polymers, peptides, or ligands, have improved their stability, targeting capability, and circulation time. SeNP-based systems have demonstrated unique anticancer, antimicrobial, and anti-inflammatory activities, as they can function as drug carriers and active therapeutic agents. The surface of SeNPs has been functionalized with ligands such as …

Application Of Bioactive Materials Primary Cilia As A Novel Delivery Vehicle, Ayan K. Barui, Farideh Amirrad, Vansh Goel, Sharareh Ohadi, Rajasekharreddy Pala, Ashraf M. Mohieldin, Andromeda M. Nauli, Surya M. Nauli

Pharmacy Faculty Articles and Research

Primary cilia are hair-like structured cell organelles functioning as cellular antennae with chemosensory and mechanosensory roles. Dysfunction of cilia results in ciliopathies, including renovascular diseases (polycystic kidneys, hypertension, aneurysm), mental impedances (Alzheimer's disease, Parkinson's disease, dementia), metabolic diseases (obesity, developmental skeleton defects), blindness, and so on. With a diameter of 150 nm, cilia can be cleaved, released and circulated in the body as injury biomarkers. We here assessed the potential use of isolated cilia as a novel delivery vehicle. Cilia were isolated from renal epithelial cells, and a specific-targeting chemotherapeutic was designed on the cilia. The data show a remarkable …

Exosomes And Encapsulated Exomirs In Breast Cancer: Theragnostic Applications And Clinical Implications, Muhammad Imran Sajid, Shafia Bukhari, Hamid Ilyas, Rubina Malik, Minahil Fatima, Rakesh Kumar Tiwari, Surya M. Nauli, Khawaja Husnain Haider

Pharmacy Faculty Books and Book Chapters

Exosomes, released by cells, are small vesicles that have emerged as critical theranostic tools in breast cancer due to their unique ability to transport diverse biomolecules such as proteins, lipids, and RNAs, including microRNAs (ExomiRs). These vesicles are critical in modulating the tumor microenvironment, driving processes like cancer proliferation, invasion, metastasis, and drug resistance. Exosomal microRNAs such as ExomiR-21, ExomiR-1246, and ExomiR-155, with their profound influence on the gene expressions in the recipient cells, are the unsung heroes in tumor progression and immune modulation. This chapter delves into exosome's dual diagnostic and therapeutic potential in breast cancer. It highlights their …

Folic Acid-Decorated Lipidic Nanocapsules Co-Loaded With Atorvastatin And Curcumin To Enhance Glioma Targeting In Mice, Mahitab Bayoumi, John Youshia, Osama Abdelkawy, Sara Abdelgaber, Mona Arafa, Maha Nasr, Omaima Sammour

Pharmacy

Background: Glioma remains an intractable and highly aggressive brain tumor, mainly due to the daunting obstacle presented by the blood-brain barrier (BBB). To overcome this challenge and enhance therapeutic efficacy, a dual-drug delivery system was engineered. This system co-encapsulated curcumin, a nutraceutical with multitargeted anticancer potential, with atorvastatin calcium, a repurposed anticancer agent, within lipidic nanocapsules (LNCs). Methods: LNCs were prepared via the phase inversion temperature method and optimized using a Box–Behnken design. The optimized LNCs were subsequently functionalized with folic acid (FA) to enable active targeting. FA-LNCs were characterized using, XPS, TEM, in vitro release, and MTT cytotoxicity …

A Review Of 3d Printing Technology In Drug Design Applications, Hasanain Shakir Mahmood, Jinan M. Al-Mousawy, Jamal Ali Ashoor, Ashti M.H. Saeed, Alaa Abdul Razzaq Al-Nuaimi, Pegah Khosravian

Maaen Journal for Medical Sciences

Sustainable technologies such as Additive manufacturing or three-dimensional printing (3D printing) have resulted in drastic changes in a number of industries including healthcare and pharmaceuticals. The current review focuses on the achievements accomplished on the effectiveness of three-dimensional printing in the field of drug designing and development. This technology is very precise and can be customized and that gives a way of developing complicated drug delivery systems and individualized medications. Promising areas of focus are the development of particular formulations of medicinal preparations, identification of new approaches to the drug release and potential creation of specific drug production for specific …

Harnessing Exosomes As A Platform For Drug Delivery In Breast Cancer: A Systematic Review For In Vivo And In Vitro Studies, Abdulwahab Teflischi Gharavi, Saeed Irian, Azadeh Niknejad, Keykavous Parang, Mona Salimi

Pharmacy Faculty Articles and Research

Breast cancer remains a significant global health concern, emphasizing the critical need for effective treatment strategies, especially targeted therapies. This systematic review summarizes the findings from in vitro and in vivo studies regarding the therapeutic potential of exosomes as drug delivery platforms in the field of breast cancer treatment. A comprehensive search was conducted across bibliographic datasets, including Web of Science, PubMed, and Scopus, using relevant queries from several related published articles and the Medical Subject Headings Database. Then, all morphological, biomechanical, histopathological, and cellular-molecular outcomes were systematically collected. A total of 30 studies were identified based on the Preferred …

Carfilzomib-Loaded Ternary Polypeptide Nanoparticles Stabilized By Polycationic Complexation, Preye Mike Agbana, Ji Eun Park, Piotr G. Rychahou, Kyung-Bo Kim, Younsoo Bae

Markey Cancer Center Faculty Publications

Carfilzomib (CFZ) is a second-generation proteasome inhibitor showing great efficacy in multiple myeloma treatment, yet its clinical applications for other diseases such as solid cancers are limited due to low aqueous solubility and poor biostability. Ternary polypeptide nanoparticles (tPNPs) are drug carriers that we previ- ously reported to overcome these pharmaceutical limitations by entrapping CFZ in the core of the nanopar- ticles and protecting the drugs from degradation in biological media. However, preclinical studies revealed that tPNPs would require further improvement in particle stability to suppress initial burst drug release and thus achieve prolonged inhibition of proteasome activity with CFZ …

Right Treatment Wrong Time: Immunotherapy Administration Post-Radiotherapy Decreases Tumor Burden In A Preclinical Model Of Brain Metastasis, Kathryn Elizabeth Blethen

Graduate Theses, Dissertations, and Problem Reports (ETD)

This dissertation (a) provided an in-depth literature review of methods to modulate the blood-brain and blood-tumor barriers to increase drug delivery and efficacy in brain metastases, (b) evaluated the effects of whole-brain radiation therapy on the blood-brain barrier in immunocompetent and immunocompromised mouse models and proposed a mechanism by which the immune response to radiation disrupts the blood-brain barrier, and (c) developed a syngeneic lung cancer brain metastasis model to determine the impact of coordinated immunotherapy administration with radiotherapy. The blood-brain barrier is an impediment to drug delivery to the brain. The inherent leakiness of the blood-tumor barrier does not …

Nanotherapeutics And Hiv: Four Decades Of Infection Canvass The Quest For Drug Development Using Nanomedical Technologies, Bhupender S. Chhikara, Nirpendra Singh, Poonam, Parveen Bazard, Rajender S. Varma, Keykavous Parang

Pharmacy Faculty Articles and Research

We have seen four decades of human struggle to cure or eradicate HIV infection since the first clinical detection of HIV infection. Various developed drugs such as nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors, integrase inhibitors, microbicides, and others have known restrictions, such as side effects and resistance development when used alone, and hidden reservoir of the virus, which have opened the gates for the involvement of nanomedicine associated systems, particularly for latent sites of HIV infection. The nanotechnological vehicles, such as liposomes, dendrimers, metal nanoparticles, polymeric nanocapsules/particles, surfactants, and targeted vehicles have become part …

Hybrid Cyclic-Linear Cell-Penetrating Peptides Containing Alternative Positive And Hydrophobic Residues As Molecular Transporters, Sorour Khayyatnejad Shoushtari

Pharmaceutical Sciences (MS) Theses

The cell membrane properties create a significant obstacle in intracellular delivery of cell-impermeable and negatively charged molecules. Amphiphilic cyclic peptides containing alternative arginine and tryptophan such as [WR]₅ have been shown to enhance the transport of cargo molecules across the cell membrane. Herein, we report the synthesis and biological evaluation of a novel series of hybrid cyclic-linear peptides containing alternative positive and hydrophobic amino acids on the ring and side-chain [(RW)₅]K(RW)_X (X=1-5) to compare their molecular transporter efficiency. The peptides were synthesized through Fmoc solid-phase peptide synthesis. Final compounds were purified by a reversed-phase HPLC (High …

Click-Free Synthesis Of A Multivalent Tricyclic Peptide As A Molecular Transporter, Sumit Kumar, Dindyal Mandal, Shaima Ahmed El-Mowafi, Saghar Mozaffari, Rakesh Kumar Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

The cellular delivery of cell-impermeable and water-insoluble molecules remains an ongoing challenge to overcome. Previously, we reported amphipathic cyclic peptides c[WR]₄ and c[WR]₅ consisting of alternate arginine and tryptophan residues as nuclear-targeting molecular transporters. These peptides contain an optimal balance of positive charge and hydrophobicity, which is required for interactions with the phospholipid bilayer to facilitate their application as a drug delivery system. To further optimize them, we synthesized and evaluated a multivalent tricyclic peptide as an efficient molecular transporter. The monomeric cyclic peptide building blocks were synthesized using Fmoc/tBu solid-phase chemistry and cyclization in the …

Prospects For Rnai Therapy Of Covid-19, Hasan Uludağ, Kylie Parent, Hamidreza Montazeri Aliabadi, Azita Haddadi

Pharmacy Faculty Articles and Research

COVID-19 caused by the SARS-CoV-2 virus is a fast emerging disease with deadly consequences. The pulmonary system and lungs in particular are most prone to damage caused by the SARS-CoV-2 infection, which leaves a destructive footprint in the lung tissue, making it incapable of conducting its respiratory functions and resulting in severe acute respiratory disease and loss of life. There were no drug treatments or vaccines approved for SARS-CoV-2 at the onset of pandemic, necessitating an urgent need to develop effective therapeutics. To this end, the innate RNA interference (RNAi) mechanism can be employed to develop front line therapies against …

Comparative Molecular Transporter Properties Of Cyclic Peptides Containing Tryptophan And Arginine Residues Formed Through Disulfide Cyclization, Eman H. M. Mohammed, Dindyal Mandal, Saghar Mozaffari, Magdy Abdel-Hamied Zahran, Amany Mostafa Osman, Rakesh Kumar Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

We have previously reported cyclic cell-penetrating peptides [WR]₅ and [WR]₄ as molecular transporters. To optimize further the utility of our developed peptides for targeted therapy in cancer cells using the redox condition, we designed a new generation of peptides and evaluated their cytotoxicity as well as uptake behavior against different cancer cell lines. Thus, cyclic [C(WR)_xC] and linear counterparts (C(WR)_xC), where x = 4–5, were synthesized using Fmoc/tBu solid-phase peptide synthesis, purified, and characterized. The compounds did not show any significant cytotoxicity (at 25 µM) against ovarian (SK-OV-3), leukemia (CCRF-CEM), gastric adenocarcinoma (CRL-1739), breast …

Development Of Novel Therapies For The Treatment Of Inflammatory Bowel Disease, Shrey Kanvinde

Theses & Dissertations

Inflammatory bowel disease (IBD) is a chronic and remittent inflammation of the gastrointestinal tract (GIT). Despite extensive research efforts, there is no cure nor a well-defined pathogenesis for IBD. Loss of epithelial barrier function, increased colonic immune cell infiltration and upregulation of pro-inflammatory cytokines are the hallmarks of IBD. Despite treatments like painkillers, aminosalicylates, steroids, and biologics, almost 70% patients require surgery at least once in their life time. The main limitation with most of the current treatments is they are either absorbed systemically or administered systemically resulting in adverse side effects. As a result, there is a huge unmet …

Delivery Of Small Molecule And Rna For The Treatment Of Type 1 Diabetes And Prostate Cancer, Di Wen

Theses & Dissertations

The aim of this thesis is to develop combination therapy using a small molecule and RNA including siRNA, shRNA, or miRNA inhibitor for the treatment of type 1 diabetes and prostate cancer. New amphiphilic biodegradable polymers capable of co-delivering small hydrophobic molecules and RNAs or human bone marrow-derived mesenchymal stem cell (hBMSC) for co-delivery of an shRNA and a miRNA inhibitor were used as drug delivery platform. The drug delivery properties were evaluated in vitro and in vivo islet transplantation, subcutaneous and orthotopic prostate cancer models.

In Chapter 1, an overview of prostate cancer, the role of miRNA and …

Novel Ph-Sensitive Cyclic Peptides, Dhammika Weerakkody, Anna Moshnikova, Naglaa Salem El-Sayed, Ramona-Cosima Adochite, Gregory Slaybaugh, Jovana Golijanin, Rakesh Tiwari, Oleg A. Andreev, Keykavous Parang, Yana K. Reshetnyak

Pharmacy Faculty Articles and Research

A series of cyclic peptides containing a number of tryptophan (W) and glutamic acid (E) residues were synthesized and evaluated as pH-sensitive agents for targeting of acidic tissue and pH-dependent cytoplasmic delivery of molecules. Biophysical studies revealed the molecular mechanism of peptides action and localization within the lipid bilayer of the membrane at high and low pHs. The symmetric, c[(WE)4WC], and asymmetric, c[E4W5C], cyclic peptides translocated amanitin, a polar cargo molecule of similar size, across the lipid bilayer and induced cell death in a pH- and concentration-dependent manner. Fluorescently-labelled peptides were evaluated for targeting of acidic 4T1 mammary tumors in …

Calcium Phosphate As A Key Material For Socially Responsible Tissue Engineering, Vuk Uskoković, Victoria M. Wu

Pharmacy Faculty Articles and Research

Socially responsible technologies are designed while taking into consideration the socioeconomic, geopolitical and environmental limitations of regions in which they will be implemented. In the medical context, this involves making therapeutic platforms more accessible and affordable to patients in poor regions of the world wherein a given disease is endemic. This often necessitates going against the reigning trend of making therapeutic nanoparticles ever more structurally complex and expensive. However, studies aimed at simplifying materials and formulations while maintaining the functionality and therapeutic response of their more complex counterparts seldom provoke a significant interest in the scientific community. In this review …

Phase Composition Control Of Calcium Phosphate Nanoparticles For Tunable Drug Delivery Kinetics And Treatment Of Osteomyelitis. Part 1: Preparation And Drug Release, Vuk Uskoković, Tejal A. Dasai

Pharmacy Faculty Articles and Research

Developed in this study is a multifunctional material for simultaneous osseoinduction and drug delivery, potentially applicable in the treatment of osteomyelitis. It is composed of agglomerates of nanoparticles of calcium phosphate (CAP) with different monophasic contents. The drug loading capacity and the release kinetics were investigated on two model drug compounds with different chemical structures, sizes and adsorption propensities: bovine serum albumin and fluorescein. Loading of CAP powders with small molecule drugs was achieved by physisorption and desiccation-induced agglomeration of nanoparticulate subunits into microscopic blocks. The material dissolution rate and the drug release rate depended on the nature of the …

Phase Composition Control Of Calcium Phosphate Nanoparticles For Tunable Drug Delivery Kinetics And Treatment Of Osteomyelitis. Part 2: Antibacterial And Osteoblastic Response, Vuk Uskoković, Tejal A. Dasai

Pharmacy Faculty Articles and Research

Osteomyelitis has been traditionally treated by the combination of long-term antibiotic therapies and surgical removal of diseased tissue. The multifunctional material was developed in this study with the aim to improve this therapeutic approach by: (a) enabling locally delivered and sustained release of antibiotics at a tunable rate, so as to eliminate the need for repetitive administration of systemically distributed antibiotics; and (b) controllably dissolving itself, so as to promote natural remineralization of the portion of bone lost to disease. We report hereby on the effect of the previously synthesized calcium phosphates (CAPs) with tunable solubilities and drug release time …

Archaeosomes And Tetraether Lipid Liposome, Hans-Joachim Freisleben

Majalah Ilmu Kefarmasian

Archaea have phytanyl ether lipids which is one of the characteristics that separates them from bacteria and eukaryotes. Some archaea have also unique membrane spanning tetrae ther lipids (T EL); in Sulfolobus and Ihermoplasma species these TELmake up the majority of total membrane lipids. Archaeal lipids are able to form stable liposomal structures, both from membrane factions, mainly the polar membrane fraction, i.e. archaeosomes, or from highly purified TEL (tetraether lipid liposomes). Liposomes of the main polar lipid (MPL) from thermoacidophilic archaeon Ihermoplasma acidophilum were thoroughly inevstigated. Archaeosomes and TEL liposomes exhibit extremely low proton permeability and high stability at …

Nanocrystals Of Chemotherapeutic Agents For Cancer Theranostics: Development And In Vitro And In Vivo Evaluation, Christin P. Hollis

Theses and Dissertations--Pharmacy

The majority of pharmacologically active chemotherapeutics are poorly water soluble. Solubilization enhancement by the utilization of organic solvents often leads to adverse side effects. Nanoparticle-based cancer therapy, which is passively targeted to the tumor tissue via the enhanced permeation and retention effect, has been vastly developed in recent years. Nanocrystals, which exist as crystalline and carry nearly 100% drug loading, has been explored for delivering antineoplastic agents. Additionally, the hybrid nanocrystal concept offers a novel and simple way to integrate imaging agents into the drug crystals, enabling the achievement of theranostics. The overall objective of this dissertation is to formulate …

Nanofabrication Of Halloysite-Pcl Composite Scaffolds And Functionalization Of Titanium For Tissue Regeneration, Shraddha Parshottambhai Patel

Doctoral Dissertations

Major medical needs may be achieved through regenerative medicine. Nanotechnology has triggered a research revolution in many important areas such as the biomedical sciences and bioengineering at the molecular level which has grown significantly due to the availability of new analytical applications and tools based on nanotechnology. Clinical conditions and diseases being targeted by nanotechnology research include burns, Alzheimer's and Parkinson's disease, implant failure, improved wound healing, birth defects, osteoporosis and congestive heart defects. Therapeutic use of growth factors and drugs to stimulate the production and/or function of endogenous cells represents a key area of regenerative medicine. The development of …

Ultrasonic Assisted Layer-By-Layer Assembly For Stable Nanocolloids Of Curcumin And Paclitaxel, Zhiguo Zheng

Doctoral Dissertations

Researchers have been trying to fight cancer with synthesis of new bioactive compounds but many of these novel drugs have low solubility in water and it is difficult to deliver them into a patient's body. One way of solving this particular problem is to use nanoscale drug delivery systems. In this dissertation, we describe using an ultrasonic assisted layer-by-layer encapsulation process to prepare anti-cancer drugs with 50∼200 nm particle size with designed coating to achieve sustained release and target delivery.

Two methods for systematic manufacture of low solubility anti-cancer drug nanoparticles were proposed: I) Top-down approach to breakdown larger drug …