Abstract:Nanoparticle morphology (size, shape, and composition) and surface chemistry are the determining factors underpinning the efficacy of such materials in therapeutic applications. The size, shape, and surface chemistry of a nanoparticle can strongly influence key properties such as interactions with diverse biological fluids and interfaces and, in turn, impact the delivery of bioactive cargo, modulating therapeutic performance. This is exemplified in ocular drug delivery, where potential therapeutics must naviga… Show more
“…Our recent ex vivo study demonstrated retinal permeation of small liposomes and tubular polymersomes [20,29]. Small particle size and non-viscous polymersome formulations enable use of small injection needles (in this study 30 G), representing another clinical advantage compared to the implants.…”
Section: Discussionmentioning
confidence: 71%
“…The mean molecular weights (M n ) of all PPP copolymers for polymersomes were in the range of 10.4-14.4 kDa, and polydispersities were 1.13-1.23. The properties of PEG-PTMC polymers for polymeric micelles were described previously [20].…”
Section: Characterization Of Polymeric Micelles and Polymersomesmentioning
Posterior eye tissues, such as retina, are affected in many serious eye diseases, but drug delivery to these targets is challenging due to various anatomical eye barriers. Intravitreal injections are widely used, but the intervals between invasive injections should be prolonged. We synthesized and characterized (1H NMR, gel permeation chromatography) block copolymers of poly(ethylene glycol), poly(caprolactone), and trimethylene carbonate. These polymers self-assembled to polymersomes and polymeric micelles. The mean diameters of polymersomes and polymeric micelles, about 100 nm and 30–50 nm, respectively, were obtained with dynamic light scattering. Based on single particle tracking and asymmetric flow field-flow fractionation, the polymeric micelles and polymersomes were stable and diffusible in the vitreous. The materials did not show cellular toxicity in cultured human umbilical vein endothelial cells in the Alamar Blue Assay. Pharmacokinetics of the intravitreal nanocarriers in the rabbits were evaluated using in vivo fluorophotometry. The half-lives of the polymersomes (100 nm) and the micelles (30 nm) were 11.4–32.7 days and 4.3–9.5 days. The intravitreal clearance values were 1.7–8.7 µL/h and 3.6–5.4 µL/h for polymersomes and polymeric micelles, respectively. Apparent volumes of distribution of the particles in the rabbit vitreous were 0.6–1.3 mL for polymeric micelles and 1.9–3.4 mL for polymersomes. Polymersomes were found in the vitreous for at least 92 days post-dosing. Furthermore, fundus imaging revealed that the polymersomes accumulated near the optic nerve and retained there even at 111 days post-injection. Polymersomes represent a promising technology for controlled and site-specific drug delivery in the posterior eye segment.
“…Our recent ex vivo study demonstrated retinal permeation of small liposomes and tubular polymersomes [20,29]. Small particle size and non-viscous polymersome formulations enable use of small injection needles (in this study 30 G), representing another clinical advantage compared to the implants.…”
Section: Discussionmentioning
confidence: 71%
“…The mean molecular weights (M n ) of all PPP copolymers for polymersomes were in the range of 10.4-14.4 kDa, and polydispersities were 1.13-1.23. The properties of PEG-PTMC polymers for polymeric micelles were described previously [20].…”
Section: Characterization Of Polymeric Micelles and Polymersomesmentioning
Posterior eye tissues, such as retina, are affected in many serious eye diseases, but drug delivery to these targets is challenging due to various anatomical eye barriers. Intravitreal injections are widely used, but the intervals between invasive injections should be prolonged. We synthesized and characterized (1H NMR, gel permeation chromatography) block copolymers of poly(ethylene glycol), poly(caprolactone), and trimethylene carbonate. These polymers self-assembled to polymersomes and polymeric micelles. The mean diameters of polymersomes and polymeric micelles, about 100 nm and 30–50 nm, respectively, were obtained with dynamic light scattering. Based on single particle tracking and asymmetric flow field-flow fractionation, the polymeric micelles and polymersomes were stable and diffusible in the vitreous. The materials did not show cellular toxicity in cultured human umbilical vein endothelial cells in the Alamar Blue Assay. Pharmacokinetics of the intravitreal nanocarriers in the rabbits were evaluated using in vivo fluorophotometry. The half-lives of the polymersomes (100 nm) and the micelles (30 nm) were 11.4–32.7 days and 4.3–9.5 days. The intravitreal clearance values were 1.7–8.7 µL/h and 3.6–5.4 µL/h for polymersomes and polymeric micelles, respectively. Apparent volumes of distribution of the particles in the rabbit vitreous were 0.6–1.3 mL for polymeric micelles and 1.9–3.4 mL for polymersomes. Polymersomes were found in the vitreous for at least 92 days post-dosing. Furthermore, fundus imaging revealed that the polymersomes accumulated near the optic nerve and retained there even at 111 days post-injection. Polymersomes represent a promising technology for controlled and site-specific drug delivery in the posterior eye segment.
“…Moreover, the small size of PLGA NPs and their surface-modified forms may offer several advantages like low toxicity, improved solubility, high surface area, dissolution rate and enhanced biodistribution. 40 – 42 Figure 6 Particle size distribution and zeta potential of ( A ) PLGA NPs, ( B ) 2-HP-β-CD/PLGA NPs, ( C ) trehalose/PLGA NPs, ( D ) chitosan oligosaccharide/PLGA NPs. …”
Section: Resultsmentioning
confidence: 99%
“…Moreover, the small size of PLGA NPs and their surface-modified forms may offer several advantages like low toxicity, improved solubility, high surface area, dissolution rate and enhanced biodistribution. [40][41][42] The zeta potential of the PLGA, 2-HP-β-CD/PLGA, trehalose/PLGA and chitosan oligosaccharide/PLGA NPs were (−22.46 ± 4.76), (−19.09 ± 1.99), (−16.24 ± 4.65) and (−7.12 ± 0.75) mV respectively. Since the surface…”
The trans-ocular barrier is a key factor limiting the therapeutic efficacy of triamcinolone acetonide. We developed a poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) surface modified respectively with 2-hydroxypropyl-β-cyclodextrin (2-HP-β-CD), chitosan oligosaccharide and trehalose. Determination of the drug/nanoparticles interactions, characterization of the nanoparticles, in vivo ocular compatibility tests, comparisons of their corneal permeability and their pharmacokinetics in aqueous humor were carried out. Methods: All PLGA NPs were prepared by the single emulsion and evaporation method and the drug-nanoparticle interaction was studied. The physiochemical features and in vitro corneal permeability of NPs were characterized while the aqueous humor pharmacokinetics was performed to evaluate in vivo corneal permeability of NPs. Ocular compatibility of NPs was investigated through Draize and histopathological test. Results: The PLGA NPs with lactide/glycolide ratio of 50:50 and small particle size (molecular weight 10 kDa) achieved optimal drug release and corneal permeability. Surface modification with different oligosaccharides resulted in uniform particle sizes and similar drug-nanoparticle interactions, although 2-HP-β-CD/PLGA NPs showed the highest entrapment efficiency. In vitro evaluation and aqueous humor pharmacokinetics further revealed that 2-HP-β-CD/PLGA NPs had greater trans-ocular permeation and retention compared to chitosan oligosaccharide/PLGA and trehalose/PLGA NPs. No ocular irritation in vivo was detected after applying modified/unmodified PLGA NPs to rabbit's eyes. Conclusion: 2-HP-β-CD/PLGA NPs are a promising nanoplatform for localized ocular drug delivery through topical administration.
“…As an illustration, the morphology of nanoparticles can be attributed to their properties, such as toxicity in biological applications [19]. Also, the structure and morphology of nanoparticles can influence the interaction of nanoparticles with biological fluids and interfaces and, finally, on the performance of nanoparticles in the body [50]. The surface morphology of MOFs can be investigated using SEM and FESEM (field emission scanning electron microscope) methods, and the inner structure of particles can be studied using TEM (transmission electron microscopy) [13].…”
Metal-organic frameworks (MOFs) are a fascinating class of crystalline porous materials composed of metal ions and organic ligands. Due to their attractive properties, MOFs can potentially offer biomedical field applications, such as drug delivery and imaging. This study aimed to systematically identify the affecting factors on the MOF characteristics and their effects on structural and biological characteristics. An electronic search was performed in four databases containing PubMed, Scopus, Web of Science, and Embase, using the relevant keywords. After analyzing the studies, 20 eligible studies were included in this review. As a result, various factors such as additives and organic ligand can influence the size and structure of MOFs. Additives are materials that can compete with ligand and may affect the nucleation and growth processes and, consequently, particle size. The nature and structure of ligand are influential in determining the size and structure of MOF. Moreover, synthesis parameters like the reaction time and initial reagents ratio are critical factors that should be optimized to regulate the size and structure. Of note is that the nature of the ligand and using a suitable additive can control the porosity of MOF. The more extended ligands aid in forming large pores. The choice of metallic nodes and organic ligand, and the MOF concentration are important factors since they can determine toxicity and biocompatibility of the final structure. The physicochemical properties of MOFs, such as hydrophobicity, affect the toxicity of nanoparticles. An increase in hydrophobicity causes increased toxicity of MOF. The biodegradability of MOF, as another property, depends on the organic ligand and metal ion and environmental conditions like pH. Photocleavable ligands can be served for controlled degradation of MOFs. Generally, by optimizing these affecting factors, MOFs with desirable properties will be obtained for biomedical applications.
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