| 1. |
- Wodrich, Matthew D., et al.
(författare)
-
Expedited Screening of Active and Regioselective Catalysts for the Hydroformylation Reaction
- 2018
-
Ingår i: Helvetica Chimica Acta. - : Wiley. - 1522-2675 .- 0018-019X. ; 101:9
-
Tidskriftsartikel (refereegranskat)abstract
- The discovery of new homogeneous catalysts that preferentially form one product over another in regio- or enantioselective chemical reactions has traditionally been the province of experimental chemists. Today, computational-based approaches have carved an increasingly important role, which, for computational catalytic designs, often rely on highly inefficient combinatorial-based screening methods. To increase the pace of discovery, tools capable of rapidly assessing large numbers of prospective species and identify those possessing desirable properties, such as activity and selectivity, are vital. Here, through the examination of the hydroformylation of 2-methylpropene, we demonstrate how a new tool built upon molecular volcano plots can be used to quickly predict the activity of molecular catalysts as well as estimate the intrinsic ability of each species to form one regioisomer over the other with striking accuracy. Following training and validation, these regioselective molecular volcanoes are employed to predict catalysts that preferentially form the branched product (2,2-dimethylpropanal) in violation of Keulemans’ 70-year-old law. Eighteen species (out of a total of 68 predicted) were computationally predicted to have regiomeric excess (r.e.) values > 90. Overall, these tools can be used to quickly screen the activity and selectivity of potential catalysis based on two easily computed descriptor variables.
|
|
| 2. |
- Morales, Javier O., et al.
(författare)
-
Films loaded with insulin-coated nanoparticles (ICNP) as potential platforms for peptide buccal delivery
- 2014
-
Ingår i: Colloids and Surfaces B. - : Elsevier BV. - 0927-7765 .- 1873-4367. ; 122, s. 38-45
-
Tidskriftsartikel (refereegranskat)abstract
- The goal of this investigation was to develop films containing insulin-coated nanoparticles and evaluate their performance in vitro as potential peptide delivery systems. To incorporate insulin into the films, a new antisolvent co-precipitation fabrication process was adapted to obtain insulin-coated nanoparticles (ICNPs). The ICNPs were embedded in polymeric films containing a cationic polymethacrylate derivative (ERL) or a combination of ERL with hydroxypropyl methylcellulose (HPMC). ICNP-loaded films were characterized for morphology, mucoadhesion, and insulin release. Furthermore, in vitro insulin permeation was evaluated using a cultured tridimensional human buccal mucosa model. The antisolvent co-precipitation method was successfully adapted to obtain ICNPs with 40% (w/w) insulin load, achieving 323±8nm particles with a high zeta potential of 32.4±0.8mV, indicating good stability. High yields were obtained after manufacture and the insulin content did not decrease after one month storage. ICNP-embedded films using ERL as the polymer matrix presented excellent mucoadhesive and insulin release properties. A high permeation enhancement effect was observed for ICNP-loaded ERL films in comparison with ICNP-loaded ERL-HPMC films and a control insulin solution. ICNP-loaded ERL formulations were found to be more effective in terms of film performance and insulin permeation through the human buccal mucosa model, and thus are a promising delivery system for buccal administration of a peptide such as insulin.
|
|
| 3. |
- Pilipiec, Patrick, et al.
(författare)
-
Using Machine Learning for Pharmacovigilance: A Systematic Review
- 2022
-
Ingår i: Pharmaceutics. - : MDPI. - 1999-4923 .- 1999-4923. ; 14:2
-
Forskningsöversikt (refereegranskat)abstract
- Pharmacovigilance is a science that involves the ongoing monitoring of adverse drug reactions to existing medicines. Traditional approaches in this field can be expensive and time-consuming. The application of natural language processing (NLP) to analyze user-generated content is hypothesized as an effective supplemental source of evidence. In this systematic review, a broad and multi-disciplinary literature search was conducted involving four databases. A total of 5318 publications were initially found. Studies were considered relevant if they reported on the application of NLP to understand user-generated text for pharmacovigilance. A total of 16 relevant publications were included in this systematic review. All studies were evaluated to have medium reliability and validity. For all types of drugs, 14 publications reported positive findings with respect to the identification of adverse drug reactions, providing consistent evidence that natural language processing can be used effectively and accurately on user-generated textual content that was published to the Internet to identify adverse drug reactions for the purpose of pharmacovigilance. The evidence presented in this review suggest that the analysis of textual data has the potential to complement the traditional system of pharmacovigilance.
|
|
| 4. |
- Morales, Javier O., et al.
(författare)
-
A design of experiments to optimize a new manufacturing process for high activity protein-containing submicron particles
- 2013
-
Ingår i: Drug Development and Industrial Pharmacy. - : Informa UK Limited. - 0363-9045 .- 1520-5762. ; 39:11, s. 1793-1801
-
Tidskriftsartikel (refereegranskat)abstract
- A novel method for the manufacture of protein/peptide-containing submicron particles was developed in an attempt to provide particles with increased activity while using high energy input technologies. The method consists of antisolvent co-precipitation from an aqueous solution containing both an amino acid core material (e.g. D,L-valine), and either bovine serum albumin (BSA) or lysozyme (Lys) as model proteins. The aqueous solution was added to the organic phase by means of a nebulizer to increase the total surface area of interaction for the precipitation process. Sonication proved to be an effective method to produce small particle sizes while maintaining high activity of Lys. The use of a polysorbate or sorbitan ester derivatives as stabilizers proved to be necessary to yield submicron particles. Particles with very high yields (approximately 100%) and very high activity after manufacture (approximately 100%) could be obtained. A particle size of 439.0 nm, with a yield of 48.8% and with final remaining activity of 98.7% was obtained. By studying various factors using a design of experiments strategy (DoE) we were able to establish the critical controlling factors for this new method of manufacture.
|
|
| 5. |
- Morales, Javier O., et al.
(författare)
-
Lipid nanoparticles for the topical delivery of retinoids and derivatives
- 2015
-
Ingår i: Nanomedicine. - : Future Medicine Ltd. - 1743-5889 .- 1748-6963. ; 10:2, s. 253-269
-
Tidskriftsartikel (refereegranskat)abstract
- Retinoids are lipophilic compounds that are highly used in cosmetics/therapeutics for skin disorders. Conventional formulations are limited by poor water solubility, high chemical/photochemical instability and the irritation of retinoids. Interestingly, lipid nanoparticles enable the administration of retinoids in aqueous media, providing drug stabilization and controlled release. Recently, it has been demonstrated that retinoids in solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions and nanocapsules can decrease degradation, improve targeting and enhance efficacy for the treatment of skin disorders. This article focuses on the formulation, fabrication, characterization and in vitro/in vivo evaluation of solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions and nanocapsules loaded with retinoids for skin administration. Furthermore, the incorporation of these lipid nanoparticles into secondary vehicles is discussed.
|
|
| 6. |
- Morales, Javier O., et al.
(författare)
-
Manufacture and characterization of mucoadhesive buccal films
- 2011
-
Ingår i: European journal of pharmaceutics and biopharmaceutics. - : Elsevier BV. - 0939-6411 .- 1873-3441. ; 77:2, s. 187-199
-
Tidskriftsartikel (refereegranskat)abstract
- The buccal route of administration has a number of advantages including bypassing the gastrointestinal tract and the hepatic first pass effect. Mucoadhesive films are retentive dosage forms and release drug directly into a biological substrate. Furthermore, films have improved patient compliance due to their small size and reduced thickness, compared for example to lozenges and tablets. The development of mucoadhesive buccal films has increased dramatically over the past decade because it is a promising delivery alternative to various therapeutic classes including peptides, vaccines, and nanoparticles. The "film casting process" involves casting of aqueous solutions and/or organic solvents to yield films suitable for this administration route. Over the last decade, hot-melt extrusion has been explored as an alternative manufacturing process and has yielded promising results. Characterization of critical properties such as the mucoadhesive strength, drug content uniformity, and permeation rate represent the major research areas in the design of buccal films. This review will consider the literature that describes the manufacture and characterization of mucoadhesive buccal films.
|
|
| 7. |
- Morales, Javier O., et al.
(författare)
-
Novel Nanostructured Polymeric Carriers to Enable Drug Delivery for Cardiovascular Diseases
- 2015
-
Ingår i: Current pharmaceutical design. - : Bentham Science Publishers Ltd.. - 1381-6128 .- 1873-4286. ; 21:29, s. 4276-4284
-
Tidskriftsartikel (refereegranskat)abstract
- Applications of polymeric nanotechnologies for enabling therapies for cardiovascular diseases have shown recent success. Both intravenous and oral administration have been investigated and achieved different degrees of development. While circulating polymeric nanostructured carriers are subjected to a number of interactions, smart nanoparticle design has enabled the formulation of active molecules to be delivered to specific targets for cardiovascular effects. This review aims at outlining the multiple factors that can affect the fate of polymeric nanostructured carriers in systemic circulation. With an understanding of these factors, the literature on the various polymeric nanostructured carriers is reviewed. Finally, the emerging uses of nanotechnology to formulate orally administered drugs for cardiovascular diseases are depicted.
|
|
| 8. |
- Morales, Javier O., et al.
(författare)
-
Novel strategies for the buccal delivery of macromolecules
- 2014
-
Ingår i: Drug Development and Industrial Pharmacy. - : Informa UK Limited. - 0363-9045 .- 1520-5762. ; 40:5, s. 579-590
-
Tidskriftsartikel (refereegranskat)abstract
- For years now, the delivery of small molecules through the buccal mucosal route has been described in the literature, but it has only been over the past decade that investigations into macromolecule delivery via the buccal route have sharply increased. The administration of macromolecules such as proteins and peptides, antibodies, or nucleic acids by buccal administration would be greatly enhanced due to the avoidance of the gastrointestinal conditions, rapid uptake into systemic circulation, as well as the potential for controlled drug delivery. Since macromolecules are faced with a number of specific challenges related to permeation through the epithelium, several strategies have been employed historically to improve their buccal absorption and subsequent bioavailability. Several conventional strategies to improve macromolecule penetration include the use of chemical permeation enhancers, enzyme inhibitors and the use of mucoadhesive materials acting as carriers. More recent approaches include the incorporation of the macromolecule as part of nanostructured delivery systems to further enhance targeting and delivery. This review focuses on the different permeation enhancing strategies as well as formulation design that are tailored to meet the challenges of active macromolecule delivery using the buccal mucosal route of administration.
|
|
| 9. |
- Morales, Javier O., et al.
(författare)
-
Preface for buccal drug delivery theme issue
- 2014
-
Ingår i: Drug Development and Industrial Pharmacy. - : Informa UK Limited. - 0363-9045 .- 1520-5762. ; 40:5, s. 577-578
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- During the past years, buccal drug delivery has attracted the attention of researchers looking for alternative delivery routes of administration. As an alternative to oral drug delivery, the buccal mucosal route avoids the passage through the acidic gastric environment, intestinal and bacterial enzymatic activity, absorption issues associated with the intestinal epithelium (e.g. P-glycoprotein efflux), and the first pass metabolism of the liver. Therefore, the buccal route could be a good delivery route for macromolecules and other drugs not compatible with the gastrointestinal tract environment. This "Buccal Drug Delivery" special edition of Drug Development and Industrial Pharmacy aims to bring together a range of different aspects relevant to the growing field of buccal drug delivery. The special edition includes thorough reviews of the literature, as well as original research articles touching on most prominent features related to buccal drug delivery systems, such as the move toward the use of nanotechnology in different ways to facilitate buccal drug delivery with the potential to prompt future product developments.
|
|
| 10. |
- Morales, Javier O., et al.
(författare)
-
Surfactants : their critical role in enhancing drug delivery to the lungs
- 2011
-
Ingår i: Therapeutic delivery. - : Future Science Ltd. - 2041-5990 .- 2041-6008. ; 2:5, s. 623-641
-
Tidskriftsartikel (refereegranskat)abstract
- For local lung conditions and diseases, pulmonary drug delivery has been widely used for more than 50 years now. A more recent trend involves the pulmonary route as a systemic drug-delivery target. Advantages such as avoidance of the gastrointestinal environment, different enzyme content compared with the intestine, and avoidance of first-pass metabolism make the lung an alternative route for the systemic delivery of actives. However, the lung offers barriers to absorption such as a surfactant layer, epithelial surface lining fluid, epithelial monolayer, interstitium and basement membrane, and capillary endothelium. Many delivery strategies have been developed in order to overcome these limitations. The use of surfactants is one of these approaches and their role in enhancing pulmonary drug delivery is reviewed in this article. A systematic review of the literature relating to the effect of surfactants on formulations for pulmonary delivery was conducted. Specifically, research reporting enhancement of in vivo performance was focused on. The effect of the addition of surfactants such as phospholipids, bile salts, non-ionic, fatty acids, and liposomes as phospholipid-containing carriers on the enhancement of therapeutic outcomes of drugs for pulmonary delivery was compiled. The main use attributed to surfactants in pulmonary drug delivery is as absorption enhancers by mechanisms of action not yet fully understood. Furthermore, surfactants have been used to improve the delivery of inhaled drugs in various additional strategies discussed herein.
|
|
