| 1. |
- Alvebratt, Caroline, et al.
(författare)
-
In Vitro Performance and Chemical Stability of Lipid-Based Formulations Encapsulated in a Mesoporous Magnesium Carbonate Carrier
- 2020
-
Ingår i: Pharmaceutics. - : MDPI AG. - 1999-4923 .- 1999-4923. ; 12:5
-
Tidskriftsartikel (refereegranskat)abstract
- Lipid-based formulations can circumvent the low aqueous solubility of problematic drug compounds and increase their oral absorption. As these formulations are often physically unstable and costly to manufacture, solidification has been suggested as a way to minimize these issues. This study evaluated the physicochemical stability and in vitro performance of lipid-loaded mesoporous magnesium carbonate (MMC) particles with an average pore size of 20 nm. A medium chain lipid was loaded onto the MMC carrier via physical adsorption. A modified in vitro lipolysis setup was then used to study lipid release and digestion with 1H nuclear magnetic resonance spectroscopy. The lipid loading efficiency with different solidification techniques was also evaluated. The MMC, unlike more commonly used porous silicate carriers, dissolved during the lipolysis assay, providing a rapid release of encapsulated lipids into solution. The digestion of the dispersed lipid-loaded MMC therefore resembled that of a coarse dispersion of the lipid. The stability data demonstrated minor degradation of the lipid within the pores of the MMC particles, but storage for three months did not reveal extensive degradation. To conclude, lipids can be adsorbed onto MMC, creating a solid powder from which the lipid is readily released into the solution during in vitro digestion. The chemical stability of the formulation does however merit further attention.
|
|
| 2. |
- Dening, Tahnee J., et al.
(författare)
-
Inorganic surface chemistry and nanostructure controls lipolytic product speciation and partitioning during the digestion of inorganic-lipid hybrid particles
- 2018
-
Ingår i: Journal of Colloid and Interface Science. - : Elsevier BV. - 1095-7103 .- 0021-9797. ; 532, s. 666-679
-
Tidskriftsartikel (refereegranskat)abstract
- Hypothesis: Solid-state lipid formulations, whereby liquid lipids are encapsulated in inorganic particle matrices, have attracted significant interest for drug/nutrient delivery in recent years. We hypothesized that the surface chemistry of the inorganic material used to encapsulate lipids impacts the lipase-mediated digestion and partitioning of lipolytic species between the solubilized aqueous and insoluble pellet phases. Experiments: Medium chain triglycerides were spray dried with silica nanoparticles, montmorillonite or laponite platelets to form inorganic-lipid hybrid particles. In vitro lipolysis studies were conducted under gastric (pH 1.6) and intestinal (pH 7.5) conditions, and the speciation and partitioning of lipolytic products between the aqueous and pellet phases was characterized using solution-state proton nuclear magnetic resonance and fourier transform infrared spectroscopy. Findings: Under gastric conditions, greater than 80% of all lipid species remained adsorbed within each lipolysis pellet after 60 min. Approximately 40%, 50–60% and 80–90% of all lipid species were adsorbed from solution by silica-, montmorillonite- and laponite-based particle matrices during intestinal lipolysis. Monoglycerides were preferentially adsorbed by silica, whereas triglycerides and fatty acids were adsorbed by montmorillonite and laponite. Adsorption of lipolytic products from solution is expected to impact significantly on drug/nutrient solubilization and absorption in vivo. To the best of our knowledge, this is the first report characterizing the speciation and phase behavior of lipolytic products released from solid-state lipid formulations during in vitro lipolysis studies.
|
|
| 3. |
- Wright, Leah, et al.
(författare)
-
A comparison of chitosan, mesoporous silica and poly(lactic-co-glycolic) acid nanocarriers for optimising intestinal uptake of oral protein therapeutics
- 2021
-
Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier. - 0022-3549 .- 1520-6017. ; 110:1, s. 217-227
-
Tidskriftsartikel (refereegranskat)abstract
- Efficacious oral delivery of therapeutic proteins remains challenging and nanoparticulate approaches are gaining interest for enhancing their permeability. In this study, we explore the ability for three comparably sized nanocarriers, with diverse physicochemical properties (i.e., chitosan (CSNP), mesoporous silica nanoparticles (MSNP) and poly(lactic-co-glycolic) acid (PLGA-NP)), to successfully facilitate epithelial uptake of a model protein, ovalbumin (OVA). We report the effect of nanoparticle surface chemistry and nanostructure on protein release, cell toxicity and the uptake mechanism in a Madin Darby Canine Kidney (MDCK) cell model of the intestinal epithelium. All nanocarriers exhibited bi-phasic OVA release kinetics with sustained and incomplete release after 4 days, and more pronounced release from MSNP than either polymeric nanocarriers. CSNP and MSNP displayed the highest cellular uptake, however CSNP was prone to significant dose-dependent toxicity attributed to the cationic surface charge. Approximately 25% of MSNP uptake was governed by a clathrin-independent endocytic mechanism, while CSNP and PLGA-NP uptake was not controlled via any endocytic mechanisms investigated herein. Furthermore, endosomal localisation was observed for CSNP and MSNP, but not for PLGA-NP's. These findings may assist in the optimal choice and engineering of nanocarriers for specific intestinal permeation enhancement for oral protein delivery.
|
|
| 4. |
- Dening, Tahnee J., et al.
(författare)
-
Improving Correlations Between Drug Solubilization and In Vitro Lipolysis by Monitoring the Phase Partitioning of Lipolytic Species for Lipid-Based Formulations
- 2019
-
Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 1520-6017 .- 0022-3549. ; 108:1, s. 295-304
-
Tidskriftsartikel (refereegranskat)abstract
- Solution proton nuclear magnetic resonance analysis was used in conjunction with in vitro lipolysis to elucidate the time-dependent speciation and release of lipolytic products during the digestion of lipid-loaded inorganic particles, allowing correlations to be made between the phase partitioning of lipolytic products and an encapsulated poorly soluble drug. Silicon dioxide, montmorillonite, and laponite were used to encapsulate medium chain triglycerides into solid-state lipid-based formulations (LBFs), and coumarin 102 was selected as a model poorly soluble compound. The specific inorganic carrier material used to encapsulate medium chain triglycerides significantly impacted the release and partitioning of the solubilizing lipolytic products, that is, diglycerides, monoglycerides, and fatty acids. A strong linear correlation was obtained between drug solubilization and fatty acid release to the aqueous phase (R2 = 0.996), indicating fatty acids to be the most important lipid species for enabling solubilization and potential drug absorption in vivo. This method was developed to improve upon the use of pH-stat titration for characterizing LBF digestion during in vitro lipolysis studies and is demonstrated herein to provide useful insights into how the selected inorganic carrier material impacts LBF performance when solid-state LBF powders are fabricated via adsorption.
|
|
| 5. |
- Dening, Tahnee J., et al.
(författare)
-
Spray Dried Smectite Clay Particles as a Novel Treatment against Obesity
- 2019
-
Ingår i: Pharmaceutical Research. - : Springer Science and Business Media LLC. - 1573-904X .- 0724-8741. ; 36:1
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: To explore the feasibility of spray dried smectite clay particles fabricated from montmorillonite or laponite materials for adsorbing dietary lipids and reducing rodent weight gain in vivo. Methods: Spray dried montmorillonite (SD-MMT) and spray dried laponite (SD-LAP) particles were prepared via spray drying. Particle morphology, surface area and redispersion/aggregation properties in aqueous media were characterized. The ability of SD-MMT and SD-LAP particles to inhibit lipid digestion kinetics and adsorb lipid species from solution was assessed during in vitro lipolysis using proton nuclear magnetic resonance analysis. SD-MMT and SD-LAP particles were dosed to rodents fed a high-fat diet and their effect on body weight gain was evaluated. Results: Both SD-MMT and SD-LAP particles adsorbed significant quantities of medium chain triglycerides and lipolytic products from solution during in vitro lipolysis. At a concentration of 50% w/w relative to lipid content, SD-MMT and SD-LAP particles adsorbed 42% and 94% of all lipid species, respectively. SD-MMT and SD-LAP particles also reduced the extent of rodent weight gain relative to the negative control treatment group and performed similarly to orlistat via an alternate mechanism of action. Conclusions: Spray dried smectite clay particles (SD-MMT and SD-LAP) with significant adsorptive capacities for dietary lipids and digestion products were successfully fabricated. These particles may be developed as novel anti-obesity treatments with fewer adverse effects than currently marketed treatment options.
|
|
| 6. |
- Joyce, Paul, 1989, et al.
(författare)
-
Engineering intelligent particle-lipid composites that control lipase-mediated digestion
- 2018
-
Ingår i: Advances in Colloid and Interface Science. - : Elsevier BV. - 0001-8686. ; 260, s. 1-23
-
Forskningsöversikt (refereegranskat)abstract
- Nanostructured particle-lipid composites have emerged as state-of-the-art carrier systems for poorly water-soluble bioactive molecules due to their ability to control and enhance the lipase-mediated hydrolysis of encapsulated triglycerides, leading to a subsequent improvement in the solubilisation and absorption of encapsulated species. The first generation of particle-lipid composites (i.e. silica-lipid hybrid (SLH) microparticles) were designed and fabricated by spray drying a silica nanoparticle-stabilised Pickering emulsion, to create a novel three-dimensional architecture, whereby lipid droplets were encapsulated within a porous matrix support. The development of SLH microparticles has acted as a solid foundation for the synthesis of several next generation particle-lipid composites, including polymer-lipid hybrid (PLH) and clay-lipid hybrid systems (CLH), which present lipase with unique lipid microenvironments for optimised lipolysis. This review details the methods utilised to engineer lipid hybrid particles and the strategic investigations that have been performed to determine the influence of key material characteristics on digestion enzyme activity. In doing so, this provides insight into manipulating the mechanism of lipase action through the intelligent design of lipid-based biomaterials for their use in drug delivery formulations and novel functional foods.
|
|
| 7. |
- Joyce, Paul, 1989, et al.
(författare)
-
Enhancing the cellular uptake and antibacterial activity of rifampicin through encapsulation in mesoporous silica nanoparticles
- 2020
-
Ingår i: Nanomaterials. - : MDPI AG. - 2079-4991. ; 10:4
-
Tidskriftsartikel (refereegranskat)abstract
- An urgent demand exists for the development of novel delivery systems that efficiently transport antibacterial agents across cellular membranes for the eradication of intracellular pathogens. In this study, the clinically relevant poorly water-soluble antibiotic, rifampicin, was confined within mesoporous silica nanoparticles (MSN) to investigate their ability to serve as an efficacious nanocarrier system against small colony variants of Staphylococcus aureus (SCV S. aureus) hosted within Caco-2 cells. The surface chemistry and particle size of MSN were varied through modifications during synthesis, where 40 nm particles with high silanol group densities promoted enhanced cellular uptake. Extensive biophysical analysis was performed, using quartz crystal microbalance with dissipation (QCM-D) and total internal reflection fluorescence (TIRF) microscopy, to elucidate the mechanism of MSN adsorption onto semi-native supported lipid bilayers (snSLB) and, thus, uncover potential cellular uptake mechanisms of MSN into Caco-2 cells. Such studies revealed that MSN with reduced silanol group densities were prone to greater particle aggregation on snSLB, which was expected to restrict endocytosis. MSN adsorption and uptake into Caco-2 cells correlated well with antibacterial efficacy against SCV S. aureus, with 40 nm hydrophilic particles triggering a ~2.5-log greater reduction in colony forming units, compared to the pure rifampicin. Thus, this study provides evidence for the potential to design silica nanocarrier systems with controlled surface chemistries that can be used to re-sensitise intracellular bacteria to antibiotics by delivering them to the site of infection.
|
|
| 8. |
- Joyce, Paul, 1989, et al.
(författare)
-
Modulating the Lipase-Mediated Bioactivity of Particle-Lipid Conjugates Through Changes in Nanostructure and Surface Chemistry
- 2017
-
Ingår i: European Journal of Lipid Science and Technology. - : Wiley. - 1438-7697 .- 1438-9312. ; 119:12, s. 1700213-
-
Tidskriftsartikel (refereegranskat)abstract
- The lipase-mediated hydrolysis of triglycerides can be controlled by confining lipid droplets within highly porous nanostructured particle matrices. Novel hybrid materials with varying bioactivities toward lipase have been developed by spray drying particle-stabilized emulsions to form highly organized three-dimensional architectures. In this study, the particle size, nanostructure, and surface chemistry of hybrid particles are tailored to systematically investigate the influence of material characteristics on lipase activity. This is achieved by varying (i) the spray drying process and (ii) the structure and composition of particulate colloids employed to stabilize the precursor emulsions. In all cases, the colloidal self-assembly of particles and droplets into nanostructured conjugates during the water removal process facilitated enhanced lipase activity compared to submicron triglyceride emulsions, with lipolysis kinetics increasing in the following order: polymer-lipid hybrid (PLH)
|
|
| 9. |
- Joyce, Paul, 1989, et al.
(författare)
-
Nanostructured clay particles supplement orlistat action in inhibiting lipid digestion: An in vitro evaluation for the treatment of obesity
- 2019
-
Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 135, s. 1-11
-
Tidskriftsartikel (refereegranskat)abstract
- Obesity is a rapidly growing epidemic, with over one-third of the global population classified as overweight or obese. Consequently, an urgent need exists to develop innovative approaches and technologies that regulate energy uptake, to curb the rising trend in obesity statistics. In this study, nanostructured clay (NSC)particles, fabricated by spray drying delaminated dispersions technologies that regulate energy uptake, to curb the rising trend in obesity statistics. In this study, nanostructured clay (NSC)particles, fabricated by spray drying delaminated dispersions of commercial clay platelets (Veegum® HS and LAPONITE® XLG), were delivered as complimentary, bioactive excipients with the potent lipase inhibitor, orlistat, for the inhibition of fat (lipid)hydrolysis. Simulated intestinal lipolysis studies were performed by observing changes in free fatty acid concentration and revealed that a combinatorial effect existed when NSC particles were co-administered with orlistat, as evidenced by a 1.2- to 1.6-fold greater inhibitory response over 60 min, compared to dosing orlistat alone. Subsequently, it was determined that a multifaceted approach to lipolysis inhibition was presented, whereby NSC particles adsorbed high degrees of lipid (up to 80% of all lipid species present in lipolysis media)and thus physically shielded the lipid-in-water interface from lipase access, while orlistat covalently attached and blocked the lipase enzyme active site. Thus, the ability for NSC particles to enhance the biopharmaceutical performance and potency of orlistat is hypothesised to translate into promising in vivo pharmacodynamics, where this novel approach is predicted to lead to considerably greater weight reductions for obese patients, compared to dosing orlistat alone.
|
|
| 10. |
- Joyce, Paul, 1989, et al.
(författare)
-
Polymer lipid hybrid (PLH) formulations: A synergistic approach to oral delivery of challenging therapeutics. A synergistic approach to oral delivery of challenging therapeutics
- 2020
-
Ingår i: Delivery of Drugs: Volume 2: Expectations and Realities of Multifunctional Drug Delivery Systems. ; , s. 1-27
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- In recent decades, lipid-based formulations and polymeric systems have emerged concurrently as the predominant approaches for overcoming low gastrointestinal stability/solubility and rate-limiting dissolution drawbacks that are associated with a wide range of therapeutics, including lipophilic small molecules and sensitive macromolecules. While these conventional approaches have demonstrated the ability to overcome drug absorption barriers and subsequently improve oral biopharmaceutical performance, a number of fundamental limitations have restricted the translation of promising preclinical and clinical findings into commercial success. Furthermore, the increasing complexity of novel therapeutics has amplified the demand for innovative and intelligent carrier systems that effectively transport drug molecules to the primary site of absorption. Consequently, recent focus has been attributed to designing and engineering polymer-lipid hybrid (PLH) formulations that combine the solubilization capacity of lipids with the stabilizing matrix of polymeric systems. This presents a synergistic approach to oral drug delivery with proven potential for overcoming limitations associated with the precursor systems. This chapter focuses specifically on the development of PLH systems, with emphasis placed on the relationship between nanostructure/surface chemistry and the physicochemical and biopharmaceutical performance of the hybrid formulation.
|
|
