Drug Delivery Technology Development in Canada

A special issue of Pharmaceutics (ISSN 1999-4923).

Deadline for manuscript submissions: closed (5 February 2019) | Viewed by 118191

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Guest Editor
Department of Urologic Sciences, Faculty of Medicine, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, Canada
Interests: pharmaceutics; drug delivery; formulation; drug development; translational pharmacotherapy; lipid and lipoprotein metabolism; pharmacokinetics
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College of Pharmacy and Nutrition, University of Saskatchewan, 107 Wiggins Road, Health Sciences Building, Room 3D01.5, Box 3D01-13, Saskatoon, SK S7N 5E5, Canada
Interests: nucleic acid delivery; nanodiamonds; cationic gemini lipids; self-assembling nanoparticles; small angle X-ray scattering; flow cytometry; radiopharmaceuticals
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Canada continues to have a rich history of ground-breaking research in drug delivery within academic institutions, pharmaceutical industry and the biotechnology community. Drug delivery refers to approaches, formulations, technologies, and systems for transporting a pharmaceutical compound in the body as needed to safely achieve its desired therapeutic effect. It may involve scientific site-targeting within the body, or facilitating systemic pharmacokinetics; in any case, it is typically concerned with both quantity and duration of drug presence. Drug delivery is often approached through a drug's chemical formulation, medical devices or drug-device combination products. Drug delivery is a concept heavily integrated with dosage form and route of administration, the latter sometimes even being considered part of the definition.

Drug delivery technologies modify drug release profile, absorption, distribution and elimination for the benefit of improving product efficacy and safety, as well as patient convenience and compliance

Over the past 25 years, numerous Canadian-based biotechnology companies have been formed from the inventions conceived and developed within academic institutions that have led to the development of important drug delivery products that have enhanced the landscape of drug therapy in the treatment of cancer to infectious diseases. 

This Special Issue serves to highlight and capture the contemporary progress of drug delivery within the prevailing Canadian context. We invite articles on all aspects of drug delivery sciences from pre-clinical formulation development to human clinical trials that bring to light the world-class research currently undertaken in Canada for this Special Issue.

Prof. Dr. Kishor M. Wasan
Prof. Dr. Ildiko Badea
Guest Editors

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Keywords

  • Drug Delivery
  • Pharmaceutics
  • Drug Development
  • Formulation and Dosage Form Development
  • Translational Research
  • Biologicals
  • Small Molecules
  • Clinical Trials
  • Pharmacokinetics
  • Medical Devices
  • Route of Administration

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Published Papers (18 papers)

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Editorial

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4 pages, 167 KiB  
Editorial
Drug Delivery Technology Development in Canada
by Kishor M. Wasan and Ildiko Badea
Pharmaceutics 2019, 11(10), 541; https://doi.org/10.3390/pharmaceutics11100541 - 17 Oct 2019
Viewed by 2768
Abstract
Canada has a long and rich history of ground-breaking research in drug delivery within academic institutions, pharmaceutical industry and the biotechnology community. Drug delivery refers to approaches, formulations, technologies, and systems for transporting a pharmaceutical compound in the body as needed to safely [...] Read more.
Canada has a long and rich history of ground-breaking research in drug delivery within academic institutions, pharmaceutical industry and the biotechnology community. Drug delivery refers to approaches, formulations, technologies, and systems for transporting a pharmaceutical compound in the body as needed to safely achieve its desired therapeutic effect. It may involve rational site-targeting, or facilitating systemic pharmacokinetics; in any case, it is typically concerned with both quantity and duration of the presence of the drug in the body. Drug delivery is often approached through a drug’s chemical formulation, medical devices or drug-device combination products. Drug delivery is a concept heavily integrated with dosage form development and selection of route of administration; the latter sometimes even being considered part of the definition. Drug delivery technologies modify drug release profile, absorption, distribution and elimination for the benefit of improving product efficacy and safety, as well as patient convenience and adherence. Over the past 30 years, numerous Canadian-based biotechnology companies have been formed stemming from the inventions conceived and developed within academic institutions. Many have led to the development of important drug delivery products that have enhanced the landscape of drug therapy in the treatment of cancer to infectious diseases. This Special Issue serves to highlight the progress of drug delivery within Canada. We invited articles on all aspects of drug delivery sciences from pre-clinical formulation development to human clinical trials that bring to light the world-class research currently undertaken in Canada for this Special Issue. Full article
(This article belongs to the Special Issue Drug Delivery Technology Development in Canada)

Research

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18 pages, 3463 KiB  
Article
Development of a UV-Stabilized Topical Formulation of Nifedipine for the Treatment of Raynaud Phenomenon and Chilblains
by Ellen K. Wasan, Jinying Zhao, Joshua Poteet, Munawar A. Mohammed, Jaweria Syeda, Tatiana Orlowski, Kevin Soulsbury, Jacqueline Cawthray, Amanda Bunyamin, Chi Zhang, Brian M. Fahlman and Ed S. Krol
Pharmaceutics 2019, 11(11), 594; https://doi.org/10.3390/pharmaceutics11110594 - 9 Nov 2019
Cited by 10 | Viewed by 5412
Abstract
Raynaud’s Phenomenon is a vascular affliction resulting in pain and blanching of the skin caused by excessive and prolonged constriction of arterioles, usually due to cold exposure. Nifedipine is a vasodilatory calcium channel antagonist, which is used orally as the first-line pharmacological treatment [...] Read more.
Raynaud’s Phenomenon is a vascular affliction resulting in pain and blanching of the skin caused by excessive and prolonged constriction of arterioles, usually due to cold exposure. Nifedipine is a vasodilatory calcium channel antagonist, which is used orally as the first-line pharmacological treatment to reduce the incidence and severity of attacks when other interventions fail to alleviate the condition and there is danger of tissue injury. Oral administration of nifedipine, however, is associated with systemic adverse effects, and thus topical administration with nifedipine locally to the extremities would be advantageous. However, nifedipine is subject to rapid photodegradation, which is problematic for exposed skin such as the hands. The goal of this project was to analyze the photostability of a novel topical nifedipine cream to UVA light. The effect of incorporating the photoprotectants rutin, quercetin, and/or avobenzone (BMDBM) into the nifedipine cream on the stability of nifedipine to UVA light exposure and the appearance of degradation products of nifedipine was determined. Rutin and quercetin are flavonoids with antioxidant activity. Both have the potential to improve the photostability of nifedipine by a number of mechanisms that either quench the intermolecular electron transfer of the singlet excited dihydropyridine to the nitrobenzene group or by preventing photoexcitation of nifedipine. Rutin at either 0.1% or 0.5% (w/w) did not improve the stability of nifedipine 2% (w/w) in the cream after UVA exposure up to 3 h. Incorporation of quercetin at 0.5% (w/w) did improve nifedipine stability from 40% (no quercetin) to 77% (with quercetin) of original drug concentration after 3 h UVA exposure. A combination of BMDBM and quercetin was the most effective photoprotectant for maintaining nifedipine concentration following up to 8 h UVA exposure. Full article
(This article belongs to the Special Issue Drug Delivery Technology Development in Canada)
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16 pages, 3896 KiB  
Article
Validation of Cadherin HAV6 Peptide in the Transient Modulation of the Blood-Brain Barrier for the Treatment of Brain Tumors
by Babu V. Sajesh, Ngoc H. On, Refaat Omar, Samaa Alrushaid, Brian M. Kopec, Wei-Guang Wang, Han-Dong Sun, Ryan Lillico, Ted M. Lakowski, Teruna J. Siahaan, Neal M. Davies, Pema-Tenzin Puno, Magimairajan Issai Vanan and Donald W. Miller
Pharmaceutics 2019, 11(9), 481; https://doi.org/10.3390/pharmaceutics11090481 - 17 Sep 2019
Cited by 12 | Viewed by 4788
Abstract
The blood-brain barrier (BBB) poses a major obstacle by preventing potential therapeutic agents from reaching their intended brain targets at sufficient concentrations. While transient disruption of the BBB has been used to enhance chemotherapeutic efficacy in treating brain tumors, limitations in terms of [...] Read more.
The blood-brain barrier (BBB) poses a major obstacle by preventing potential therapeutic agents from reaching their intended brain targets at sufficient concentrations. While transient disruption of the BBB has been used to enhance chemotherapeutic efficacy in treating brain tumors, limitations in terms of magnitude and duration of BBB disruption exist. In the present study, the preliminary safety and efficacy profile of HAV6, a peptide that binds to the external domains of cadherin, to transiently open the BBB and improve the delivery of a therapeutic agent, was evaluated in a murine brain tumor model. Transient opening of the BBB in response to HAV6 peptide administration was quantitatively characterized using both a gadolinium magnetic resonance imaging (MRI) contrast agent and adenanthin (Ade), the intended therapeutic agent. The effects of HAV6 peptide on BBB integrity and the efficacy of concurrent administration of HAV6 peptide and the small molecule inhibitor, Ade, in the growth and progression of an orthotopic medulloblastoma mouse model using human D425 tumor cells was examined. Systemic administration of HAV6 peptide caused transient, reversible disruption of BBB in mice. Increases in BBB permeability produced by HAV6 were rapid in onset and observed in all regions of the brain examined. Concurrent administration of HAV6 peptide with Ade, a BBB impermeable inhibitor of Peroxiredoxin-1, caused reduced tumor growth and increased survival in mice bearing medulloblastoma. The rapid onset and transient nature of the BBB modulation produced with the HAV6 peptide along with its uniform disruption and biocompatibility is well-suited for CNS drug delivery applications, especially in the treatment of brain tumors. Full article
(This article belongs to the Special Issue Drug Delivery Technology Development in Canada)
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15 pages, 2667 KiB  
Article
Inclusion Complexes of Melphalan with Gemini-Conjugated β-Cyclodextrin: Physicochemical Properties and Chemotherapeutic Efficacy in In-Vitro Tumor Models
by Waleed Mohammed-Saeid, Abdalla H Karoyo, Ronald E Verrall, Lee D Wilson and Ildiko Badea
Pharmaceutics 2019, 11(9), 427; https://doi.org/10.3390/pharmaceutics11090427 - 22 Aug 2019
Cited by 7 | Viewed by 3653
Abstract
β-cyclodextrin (βCD) has been widely explored as an excipient for pharmaceuticals and nutraceuticals as it forms stable host–guest inclusion complexes and enhances the solubility of poorly soluble active agents. To enhance intracellular drug delivery, βCD was chemically conjugated to an 18-carbon chain cationic [...] Read more.
β-cyclodextrin (βCD) has been widely explored as an excipient for pharmaceuticals and nutraceuticals as it forms stable host–guest inclusion complexes and enhances the solubility of poorly soluble active agents. To enhance intracellular drug delivery, βCD was chemically conjugated to an 18-carbon chain cationic gemini surfactant which undergoes self-assembly to form nanoscale complexes. The novel gemini surfactant-modified βCD carrier host (hereafter referred to as 18:1βCDg) was designed to combine the solubilization and encapsulation capacity of the βCD macrocycle and the cell-penetrating ability of the gemini surfactant conjugate. Melphalan (Mel), a chemotherapeutic agent for melanoma, was selected as a model for a poorly soluble drug. Characterization of the 18:1βCDg-Mel host–guest complex was carried out using 1D/2D 1H NMR spectroscopy and dynamic light scattering (DLS). The 1D/2D NMR spectral results indicated the formation of stable and well-defined 18:1βCDg-Mel inclusion complexes at the 2:1 host–guest mole ratio; whereas, host–drug interaction was attenuated at greater 18:1βCDg mole ratio due to hydrophobic aggregation that accounts for the reduced Mel solubility. The in vitro evaluations were performed using monolayer, 3D spheroid, and Mel-resistant melanoma cell lines. The 18:1βCDg-Mel complex showed significant enhancement in the chemotherapeutic efficacy of Mel with 2–3-fold decrease in Mel half maximal inhibitory concentration (IC50) values. The findings demonstrate the potential applicability of the 18:1βCDg delivery system as a safe and efficient carrier for a poorly soluble chemotherapeutic in melanoma therapy. Full article
(This article belongs to the Special Issue Drug Delivery Technology Development in Canada)
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16 pages, 4167 KiB  
Article
Drug Delivery Technology to the CNS in the Treatment of Brain Tumors: The Sherbrooke Experience
by David Fortin
Pharmaceutics 2019, 11(5), 248; https://doi.org/10.3390/pharmaceutics11050248 - 27 May 2019
Cited by 9 | Viewed by 4351
Abstract
Drug delivery to the central nervous system (CNS) remains a challenge in neuro-oncology. Despite decades of research in this field, no consensus has emerged as to the best approach to tackle this physiological limitation. Moreover, the relevance of doing so is still sometimes [...] Read more.
Drug delivery to the central nervous system (CNS) remains a challenge in neuro-oncology. Despite decades of research in this field, no consensus has emerged as to the best approach to tackle this physiological limitation. Moreover, the relevance of doing so is still sometimes questioned in the community. In this paper, we present our experience with CNS delivery strategies that have been developed in the laboratory and have made their way to the clinic in a continuum of translational research. Using the intra-arterial (IA) route as an avenue to deliver chemotherapeutics in the treatment of brain tumors, complemented by an osmotic breach of the blood-brain barrier (BBB) in specific situations, we have developed over the years a comprehensive research effort on this specialized topic. Looking at pre-clinical work supporting the rationale for this approach, and presenting results discussing the safety of the strategy, as well as results obtained in the treatment of malignant gliomas and primary CNS lymphomas, this paper intends to comprehensively summarize our work in this field. Full article
(This article belongs to the Special Issue Drug Delivery Technology Development in Canada)
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16 pages, 1560 KiB  
Article
Development and Characterization of Liposomal Formulations Containing Phytosterols Extracted from Canola Oil Deodorizer Distillate along with Tocopherols as Food Additives
by Asmita Poudel, George Gachumi, Kishor M. Wasan, Zafer Dallal Bashi, Anas El-Aneed and Ildiko Badea
Pharmaceutics 2019, 11(4), 185; https://doi.org/10.3390/pharmaceutics11040185 - 16 Apr 2019
Cited by 32 | Viewed by 4290
Abstract
Phytosterols are plant sterols recommended as adjuvant therapy for hypercholesterolemia and tocopherols are well-established anti-oxidants. However, thermo-sensitivity, lipophilicity and formulation-dependent efficacy bring challenges in the development of functional foods, enriched with phytosterols and tocopherols. To address this, we developed liposomes containing brassicasterol, campesterol [...] Read more.
Phytosterols are plant sterols recommended as adjuvant therapy for hypercholesterolemia and tocopherols are well-established anti-oxidants. However, thermo-sensitivity, lipophilicity and formulation-dependent efficacy bring challenges in the development of functional foods, enriched with phytosterols and tocopherols. To address this, we developed liposomes containing brassicasterol, campesterol and β-sitosterol obtained from canola oil deodorizer distillate, along with alpha, gamma and delta tocopherol. Three approaches; thin film hydration-homogenization, thin film hydration-ultrasonication and Mozafari method were used for formulation. Validated liquid chromatographic tandem mass spectrometry (LC-MS/MS) was utilized to determine the entrapment efficiency of bioactives. Stability studies of liposomal formulations were conducted before and after pasteurization using high temperature short time (HTST) technique for a month. Vesicle size after homogenization and ultrasonication (<200 nm) was significantly lower than by Mozafari method (>200 nm). However, zeta potential (−9 to −14 mV) was comparable which was adequate for colloidal stability. Entrapment efficiencies were greater than 89% for all the phytosterols and tocopherols formulated by all three methods. Liposomes with optimum particle size and zeta potential were incorporated in model orange juice, showing adequate stability after pasteurization (72 °C for 15 s) for a month. Liposomes containing phytosterols obtained from canola waste along with tocopherols were developed and successfully applied as a food additive using model orange juice. Full article
(This article belongs to the Special Issue Drug Delivery Technology Development in Canada)
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18 pages, 2079 KiB  
Article
Investigating the Phospholipid Effect on the Bioaccessibility of Rosmarinic Acid-Phospholipid Complex through a Dynamic Gastrointestinal in Vitro Model
by Jiahao Huang, Peter X. Chen, Michael A. Rogers and Shawn D. Wettig
Pharmaceutics 2019, 11(4), 156; https://doi.org/10.3390/pharmaceutics11040156 - 2 Apr 2019
Cited by 31 | Viewed by 3676
Abstract
Phyto-phospholipid complexes have been developed as a common way of improving the oral bioavailability of poorly absorbable phyto-pharmaceuticals; however, the complexation with phospholipids can induce positive or negative effects on the bioaccessibility of such plant-derived active ingredients in different parts of the gastrointestinal [...] Read more.
Phyto-phospholipid complexes have been developed as a common way of improving the oral bioavailability of poorly absorbable phyto-pharmaceuticals; however, the complexation with phospholipids can induce positive or negative effects on the bioaccessibility of such plant-derived active ingredients in different parts of the gastrointestinal tract (GIT). The purpose of this study was to investigate the effects of phospholipid complexation on the bioaccessibility of a rosmarinic acid-phospholipid complex (RA-PLC) using the TNO dynamic intestinal model-1 (TIM-1). Preparation of RA-PLC was confirmed using X-ray diffraction, Fourier-transform infrared spectroscopy, partition coefficient measurement, and Caco-2 monolayer permeation test. Bioaccessibility parameters in different GIT compartments were investigated. Complexation by phospholipids reduced the bioaccessibility of RA in jejunum compartment, while maintaining the ileum bioaccessibility. The overall bioaccessibility of RA-PLC was lower than the unformulated drug, suggesting that the improved oral absorption from a previous animal study could be considered as a net result of decreased bioaccessibility overwhelmed by enhanced intestinal permeability. This study provides insights into the effects of phospholipid on the bioaccessibility of hydrophilic compounds, and analyzes them based on the relationship between bioaccessibility, membrane permeability, and bioavailability. Additionally, TIM-1 shows promise in the evaluation of dosage forms containing materials with complicated effects on bioaccessibility. Full article
(This article belongs to the Special Issue Drug Delivery Technology Development in Canada)
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8 pages, 340 KiB  
Communication
Biodistribution of a Radiolabeled Antibody in Mice as an Approach to Evaluating Antibody Pharmacokinetics
by Kevin J. H. Allen, Rubin Jiao, Mackenzie E. Malo, Connor Frank and Ekaterina Dadachova
Pharmaceutics 2018, 10(4), 262; https://doi.org/10.3390/pharmaceutics10040262 - 5 Dec 2018
Cited by 15 | Viewed by 5927
Abstract
(1) Background: Monoclonal antibodies are used in the treatment of multiple conditions including cancer, autoimmune disorders, and infectious diseases. One of the initial steps in the selection of an antibody candidate for further pre-clinical development is determining its pharmacokinetics in small animal models. [...] Read more.
(1) Background: Monoclonal antibodies are used in the treatment of multiple conditions including cancer, autoimmune disorders, and infectious diseases. One of the initial steps in the selection of an antibody candidate for further pre-clinical development is determining its pharmacokinetics in small animal models. The use of mass spectrometry and other techniques to determine the fate of these antibodies is laborious and expensive. Here we describe a straightforward and highly reproducible methodology for utilizing radiolabeled antibodies for pharmacokinetics studies. (2) Methods: Commercially available bifunctional linker CHXA” and 111Indium radionuclide were used. A melanin-specific chimeric antibody A1 and an isotype matching irrelevant control A2 were conjugated with the CHXA”, and then radiolabeled with 111In. The biodistribution was performed at 4 and 24 h time points in melanoma tumor-bearing and healthy C57BL/6 female mice. (3) The biodistribution of the melanin-binding antibody showed the significant uptake in the tumor, which increased with time, and very low uptake in healthy melanin-containing tissues such as the retina of the eye and melanized skin. This biodistribution pattern in healthy tissues was very close to that of the isotype matching control antibody. (4) Conclusions: The biodistribution experiment allows us to assess the pharmacokinetics of both antibodies side by side and to make a conclusion regarding the suitability of specific antibodies for further development. Full article
(This article belongs to the Special Issue Drug Delivery Technology Development in Canada)
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18 pages, 4012 KiB  
Article
Modulation of Hypoxia-Induced Chemoresistance to Polymeric Micellar Cisplatin: The Effect of Ligand Modification of Micellar Carrier Versus Inhibition of the Mediators of Drug Resistance
by Hoda Soleymani Abyaneh, Amir Hassan Soleimani, Mohammad Reza Vakili, Rania Soudy, Kamaljit Kaur, Francesco Cuda, Ali Tavassoli and Afsaneh Lavasanifar
Pharmaceutics 2018, 10(4), 196; https://doi.org/10.3390/pharmaceutics10040196 - 21 Oct 2018
Cited by 14 | Viewed by 3822
Abstract
Hypoxia can induce chemoresistance, which is a significant clinical obstacle in cancer therapy. Here, we assessed development of hypoxia-induced chemoresistance (HICR) against free versus polymeric cisplatin micelles in a triple negative breast cancer cell line, MDA-MB-231. We then explored two strategies for the [...] Read more.
Hypoxia can induce chemoresistance, which is a significant clinical obstacle in cancer therapy. Here, we assessed development of hypoxia-induced chemoresistance (HICR) against free versus polymeric cisplatin micelles in a triple negative breast cancer cell line, MDA-MB-231. We then explored two strategies for the modulation of HICR against cisplatin micelles: a) the development of actively targeted micelles; and b) combination therapy with modulators of HICR in MDA-MB-231 cells. Actively targeted cisplatin micelles were prepared through surface modification of acetal-poly(ethylene oxide)-poly(α-carboxyl-ε-caprolactone) (acetal-PEO-PCCL) micelles with epidermal growth factor receptor (EGFR)-targeting peptide, GE11 (YHWYGYTPQNVI). Our results showed that hypoxia induced resistance against free and cisplatin micelles in MDA-MB-231 cells. A significant increase in micellar cisplatin uptake was observed in MDA-MB-231 cells that overexpress EGFR, following surface modification of micelles with GE11. This did not lead to increased cytotoxicity of micellar cisplatin, however. On the other hand, the addition of pharmacological inhibitors of key molecules involved in HICR in MDA-MB-231 cells, i.e., inhibitors of hypoxia inducing factor-1 (HIF-1) and signal transducer and activator of transcription 3 (STAT3), substantially enhanced the cytotoxicity of free and cisplatin micelles. The results indicated the potential benefit of combination therapy with HIF-1 and STAT3 inhibitors in overcoming HICR to free or micellar cisplatin. Full article
(This article belongs to the Special Issue Drug Delivery Technology Development in Canada)
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16 pages, 3269 KiB  
Article
DOX-Vit D, a Novel Doxorubicin Delivery Approach, Inhibits Human Osteosarcoma Cell Proliferation by Inducing Apoptosis While Inhibiting Akt and mTOR Signaling Pathways
by Zaid H. Maayah, Ti Zhang, Marcus Laird Forrest, Samaa Alrushaid, Michael R. Doschak, Neal M. Davies and Ayman O. S. El-Kadi
Pharmaceutics 2018, 10(3), 144; https://doi.org/10.3390/pharmaceutics10030144 - 4 Sep 2018
Cited by 14 | Viewed by 4606
Abstract
Doxorubicin (DOX) is a very potent and effective anticancer agent. However, the effectiveness of DOX in osteosarcoma is usually limited by the acquired drug resistance. Recently, Vitamin D (Vit-D) was shown to suppress the growth of many human cancer cells. Taken together, we [...] Read more.
Doxorubicin (DOX) is a very potent and effective anticancer agent. However, the effectiveness of DOX in osteosarcoma is usually limited by the acquired drug resistance. Recently, Vitamin D (Vit-D) was shown to suppress the growth of many human cancer cells. Taken together, we synthesized DOX-Vit D by conjugating Vit-D to DOX in order to increase the delivery of DOX into cancer cells and mitigate the chemoresistance associated with DOX. For this purpose, MG63 cells were treated with 10 µM DOX or DOX-Vit D for 24 h. Thereafter, MTT, real-time PCR and western blot analysis were used to determine cell proliferation, genes and proteins expression, respectively. Our results showed that DOX-Vit D, but not DOX, significantly elicited an apoptotic signal in MG63 cells as evidenced by induction of death receptor, Caspase-3 and BCLxs genes. Mechanistically, the DOX-Vit D-induced apoptogens were credited to the activation of p-JNK and p-p38 signaling pathway and the inhibition of proliferative proteins, p-Akt and p-mTOR. Our findings propose that DOX-Vit D suppressed the growth of MG63 cells by inducing apoptosis while inhibiting cell survival and proliferative signaling pathways. DOX-Vit D may serve as a novel drug delivery approach to potentiate the delivery of DOX into cancer cells. Full article
(This article belongs to the Special Issue Drug Delivery Technology Development in Canada)
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Review

Jump to: Editorial, Research, Other

12 pages, 2784 KiB  
Review
Development and Characterization of the Solvent-Assisted Active Loading Technology (SALT) for Liposomal Loading of Poorly Water-Soluble Compounds
by Griffin Pauli, Wei-Lun Tang and Shyh-Dar Li
Pharmaceutics 2019, 11(9), 465; https://doi.org/10.3390/pharmaceutics11090465 - 9 Sep 2019
Cited by 67 | Viewed by 7510
Abstract
A large proportion of pharmaceutical compounds exhibit poor water solubility, impacting their delivery. These compounds can be passively encapsulated in the lipid bilayer of liposomes to improve their water solubility, but the loading capacity and stability are poor, leading to burst drug leakage. [...] Read more.
A large proportion of pharmaceutical compounds exhibit poor water solubility, impacting their delivery. These compounds can be passively encapsulated in the lipid bilayer of liposomes to improve their water solubility, but the loading capacity and stability are poor, leading to burst drug leakage. The solvent-assisted active loading technology (SALT) was developed to promote active loading of poorly soluble drugs in the liposomal core to improve the encapsulation efficiency and formulation stability. By adding a small volume (~5 vol%) of a water miscible solvent to the liposomal loading mixture, we achieved complete, rapid loading of a range of poorly soluble compounds and attained a high drug-to-lipid ratio with stable drug retention. This led to improvements in the circulation half-life, tolerability, and efficacy profiles. In this mini-review, we summarize our results from three studies demonstrating that SALT is a robust and versatile platform to improve active loading of poorly water-soluble compounds. We have validated SALT as a tool for improving drug solubility, liposomal loading efficiency and retention, stability, palatability, and pharmacokinetics (PK), while retaining the ability of the compounds to exert pharmacological effects. Full article
(This article belongs to the Special Issue Drug Delivery Technology Development in Canada)
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29 pages, 2166 KiB  
Review
Controlled Drug Delivery Systems for Oral Cancer Treatment—Current Status and Future Perspectives
by Farinaz Ketabat, Meenakshi Pundir, Fatemeh Mohabatpour, Liubov Lobanova, Sotirios Koutsopoulos, Lubomir Hadjiiski, Xiongbiao Chen, Petros Papagerakis and Silvana Papagerakis
Pharmaceutics 2019, 11(7), 302; https://doi.org/10.3390/pharmaceutics11070302 - 30 Jun 2019
Cited by 93 | Viewed by 13889
Abstract
Oral squamous cell carcinoma (OSCC), which encompasses the oral cavity-derived malignancies, is a devastating disease causing substantial morbidity and mortality in both men and women. It is the most common subtype of the head and neck squamous cell carcinoma (HNSCC), which is ranked [...] Read more.
Oral squamous cell carcinoma (OSCC), which encompasses the oral cavity-derived malignancies, is a devastating disease causing substantial morbidity and mortality in both men and women. It is the most common subtype of the head and neck squamous cell carcinoma (HNSCC), which is ranked the sixth most common malignancy worldwide. Despite promising advancements in the conventional therapeutic approaches currently available for patients with oral cancer, many drawbacks are still to be addressed; surgical resection leads to permanent disfigurement, altered sense of self and debilitating physiological consequences, while chemo- and radio-therapies result in significant toxicities, all affecting patient wellbeing and quality of life. Thus, the development of novel therapeutic approaches or modifications of current strategies is paramount to improve individual health outcomes and survival, while early tumour detection remains a priority and significant challenge. In recent years, drug delivery systems and chronotherapy have been developed as alternative methods aiming to enhance the benefits of the current anticancer therapies, while minimizing their undesirable toxic effects on the healthy non-cancerous cells. Targeted drug delivery systems have the potential to increase drug bioavailability and bio-distribution at the site of the primary tumour. This review confers current knowledge on the diverse drug delivery methods, potential carriers (e.g., polymeric, inorganic, and combinational nanoparticles; nanolipids; hydrogels; exosomes) and anticancer targeted approaches for oral squamous cell carcinoma treatment, with an emphasis on their clinical relevance in the era of precision medicine, circadian chronobiology and patient-centred health care. Full article
(This article belongs to the Special Issue Drug Delivery Technology Development in Canada)
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15 pages, 510 KiB  
Review
A Snapshot of Transdermal and Topical Drug Delivery Research in Canada
by Mahdi Roohnikan, Elise Laszlo, Samuel Babity and Davide Brambilla
Pharmaceutics 2019, 11(6), 256; https://doi.org/10.3390/pharmaceutics11060256 - 1 Jun 2019
Cited by 24 | Viewed by 4930
Abstract
The minimally- or non-invasive delivery of therapeutic agents through the skin has several advantages compared to other delivery routes and plays an important role in medical care routines. The development and refinement of new technologies is leading to a drastic expansion of the [...] Read more.
The minimally- or non-invasive delivery of therapeutic agents through the skin has several advantages compared to other delivery routes and plays an important role in medical care routines. The development and refinement of new technologies is leading to a drastic expansion of the arsenal of drugs that can benefit from this delivery strategy and is further intensifying its impact in medicine. Within Canada, as well, a few research groups have worked on the development of state-of-the-art transdermal delivery technologies. Within this short review, we aim to provide a critical overview of the development of these technologies in the Canadian environment. Full article
(This article belongs to the Special Issue Drug Delivery Technology Development in Canada)
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38 pages, 5646 KiB  
Review
Plant/Bacterial Virus-Based Drug Discovery, Drug Delivery, and Therapeutics
by Esen Sokullu, Hoda Soleymani Abyaneh and Marc A. Gauthier
Pharmaceutics 2019, 11(5), 211; https://doi.org/10.3390/pharmaceutics11050211 - 3 May 2019
Cited by 36 | Viewed by 7748
Abstract
Viruses have recently emerged as promising nanomaterials for biotechnological applications. One of the most important applications of viruses is phage display, which has already been employed to identify a broad range of potential therapeutic peptides and antibodies, as well as other biotechnologically relevant [...] Read more.
Viruses have recently emerged as promising nanomaterials for biotechnological applications. One of the most important applications of viruses is phage display, which has already been employed to identify a broad range of potential therapeutic peptides and antibodies, as well as other biotechnologically relevant polypeptides (including protease inhibitors, minimizing proteins, and cell/organ targeting peptides). Additionally, their high stability, easily modifiable surface, and enormous diversity in shape and size, distinguish viruses from synthetic nanocarriers used for drug delivery. Indeed, several plant and bacterial viruses (e.g., phages) have been investigated and applied as drug carriers. The ability to remove the genetic material within the capsids of some plant viruses and phages produces empty viral-like particles that are replication-deficient and can be loaded with therapeutic agents. This review summarizes the current applications of plant viruses and phages in drug discovery and as drug delivery systems and includes a discussion of the present status of virus-based materials in clinical research, alongside the observed challenges and opportunities. Full article
(This article belongs to the Special Issue Drug Delivery Technology Development in Canada)
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29 pages, 2716 KiB  
Review
Challenges and Recent Progress in Oral Drug Delivery Systems for Biopharmaceuticals
by Bahman Homayun, Xueting Lin and Hyo-Jick Choi
Pharmaceutics 2019, 11(3), 129; https://doi.org/10.3390/pharmaceutics11030129 - 19 Mar 2019
Cited by 526 | Viewed by 23748
Abstract
Routes of drug administration and the corresponding physicochemical characteristics of a given route play significant roles in therapeutic efficacy and short term/long term biological effects. Each delivery method has favorable aspects and limitations, each requiring a specific delivery vehicles design. Among various routes, [...] Read more.
Routes of drug administration and the corresponding physicochemical characteristics of a given route play significant roles in therapeutic efficacy and short term/long term biological effects. Each delivery method has favorable aspects and limitations, each requiring a specific delivery vehicles design. Among various routes, oral delivery has been recognized as the most attractive method, mainly due to its potential for solid formulations with long shelf life, sustained delivery, ease of administration and intensified immune response. At the same time, a few challenges exist in oral delivery, which have been the main research focus in the field in the past few years. The present work concisely reviews different administration routes as well as the advantages and disadvantages of each method, highlighting why oral delivery is currently the most promising approach. Subsequently, the present work discusses the main obstacles for oral systems and explains the most recent solutions proposed to deal with each issue. Full article
(This article belongs to the Special Issue Drug Delivery Technology Development in Canada)
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32 pages, 1701 KiB  
Review
Spatially Specific Liposomal Cancer Therapy Triggered by Clinical External Sources of Energy
by Courtney van Ballegooie, Alice Man, Mi Win and Donald T. Yapp
Pharmaceutics 2019, 11(3), 125; https://doi.org/10.3390/pharmaceutics11030125 - 16 Mar 2019
Cited by 16 | Viewed by 5010
Abstract
This review explores the use of energy sources, including ultrasound, magnetic fields, and external beam radiation, to trigger the delivery of drugs from liposomes in a tumor in a spatially-specific manner. Each section explores the mechanism(s) of drug release that can be achieved [...] Read more.
This review explores the use of energy sources, including ultrasound, magnetic fields, and external beam radiation, to trigger the delivery of drugs from liposomes in a tumor in a spatially-specific manner. Each section explores the mechanism(s) of drug release that can be achieved using liposomes in conjunction with the external trigger. Subsequently, the treatment’s formulation factors are discussed, highlighting the parameters of both the therapy and the medical device. Additionally, the pre-clinical and clinical trials of each triggered release method are explored. Lastly, the advantages and disadvantages, as well as the feasibility and future outlook of each triggered release method, are discussed. Full article
(This article belongs to the Special Issue Drug Delivery Technology Development in Canada)
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26 pages, 1333 KiB  
Review
What Drives Innovation: The Canadian Touch on Liposomal Therapeutics
by Ada W. Y. Leung, Carolyn Amador, Lin Chuan Wang, Urmi V. Mody and Marcel B. Bally
Pharmaceutics 2019, 11(3), 124; https://doi.org/10.3390/pharmaceutics11030124 - 16 Mar 2019
Cited by 18 | Viewed by 5969
Abstract
Liposomes are considered one of the most successful drug delivery systems (DDS) given their established utility and success in the clinic. In the past 40–50 years, Canadian scientists have made ground-breaking discoveries, many of which were successfully translated to the clinic, leading to [...] Read more.
Liposomes are considered one of the most successful drug delivery systems (DDS) given their established utility and success in the clinic. In the past 40–50 years, Canadian scientists have made ground-breaking discoveries, many of which were successfully translated to the clinic, leading to the formation of biotech companies, the creation of research tools, such as the Lipex Extruder and the NanoAssemblr™, as well as contributing significantly to the development of pharmaceutical products, such as Abelcet®, MyoCet®, Marqibo®, Vyxeos®, and Onpattro™, which are making positive impacts on patients’ health. This review highlights the Canadian contribution to the development of these and other important liposomal technologies that have touched patients. In this review, we try to address the question of what drives innovation: Is it the individual, the teams, the funding, and/or an entrepreneurial spirit that leads to success? From this perspective, it is possible to define how innovation will translate to meaningful commercial ventures and products with impact in the future. We begin with a brief history followed by descriptions of drug delivery technologies influenced by Canadian researchers. We will discuss recent advances in liposomal technologies, including the Metaplex technology from the author’s lab. The latter exemplifies how a nanotechnology platform can be designed based on multidisciplinary groups with expertise in coordination chemistry, nanomedicines, disease, and business to create new therapeutics that can effect better outcomes in patient populations. We conclude that the team is central to the effort; arguing if the team is entrepreneurial and well positioned, the funds needed will be found, but likely not solely in Canada. Full article
(This article belongs to the Special Issue Drug Delivery Technology Development in Canada)
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16 pages, 455 KiB  
Perspective
The Development of Oral Amphotericin B to Treat Systemic Fungal and Parasitic Infections: Has the Myth Been Finally Realized?
by Grace Cuddihy, Ellen K. Wasan, Yunyun Di and Kishor M. Wasan
Pharmaceutics 2019, 11(3), 99; https://doi.org/10.3390/pharmaceutics11030099 - 26 Feb 2019
Cited by 49 | Viewed by 4019
Abstract
Parenteral amphotericin B has been considered as first-line therapy in the treatment of systemic fungal and parasitic infections, however its use has been associated with a number of limitations including affordability, accessibility, and an array of systemic toxicities. Until very recently, it has [...] Read more.
Parenteral amphotericin B has been considered as first-line therapy in the treatment of systemic fungal and parasitic infections, however its use has been associated with a number of limitations including affordability, accessibility, and an array of systemic toxicities. Until very recently, it has been very challenging to develop a bioavailable formulation of amphotericin B due to its physical chemical properties, limited water and lipid solubility, and poor absorption. This perspective reviews several novel oral Amphotericin B formulations under development that are attempting to overcome these limitations. Full article
(This article belongs to the Special Issue Drug Delivery Technology Development in Canada)
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