Nanomedicines in the future of pediatric therapy

Sosnik, Alejandro; Carcaboso, Ángel M.

doi:10.1016/j.addr.2014.05.004

Cited by 53 publications

(28 citation statements)

References 237 publications

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“…While DRV/RTV is a highly effective combination, it is only used as a second‐line option in high‐income countries; World Health Organization guidelines do not recommend boosted DRV as first‐line due to high cost and unavailability of a heat‐stable fixed‐dose combination . Encapsulation of DRV could improve its aqueous solubility and oral bioavailability and reduce the required dose (and the cost) and thus, make this medication more affordable . In this scenario, we assessed for the first time the encapsulation of DRV within a polymeric nanocarrier.…”

Section: Resultsmentioning

confidence: 99%

Novel Poly(Ethylene Oxide)-b-Poly(Propylene Oxide) Copolymer-Glucose Conjugate by the Microwave-Assisted Ring Opening of a Sugar Lactone

Glisoni

Sosnik

2014

Macromol. Biosci.

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In this work, we investigated for the first time the conjugation of gluconolactone to a poly(ethylene oxide)-poly(propylene oxide) block copolymer by a microwave-assisted ring opening reaction. The glucosylated copolymer was obtained with high yield (90%). A conjugation extent of approximately 100% was achieved within 15 min. The modification reduced the critical micellar concentration and increased the size of the micelles. The agglutination of the modified polymeric micelles by a soluble lectin that binds glucose confirmed the recognizability of the modified nanocarrier. Finally, the solubilization of darunavir, an anti-HIV protease inhibitor, showed a sharp increase of the aqueous solubility from 91 microgram/mL to 14.2 and 18.9 mg/mL for 10% w/v pristine and glucosylated polymeric micelles, respectively.

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Section: Resultsmentioning

confidence: 99%

Novel Poly(Ethylene Oxide)-b-Poly(Propylene Oxide) Copolymer-Glucose Conjugate by the Microwave-Assisted Ring Opening of a Sugar Lactone

Glisoni

Sosnik

2014

Macromol. Biosci.

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“…The ability to maximize the concentration of the chemotherapeutic agent inside the tumor while reducing systemic exposure is one of the expected benefits of targeted nanomedicine [46]. However, the proper characterization of the distribution and fate of drug released from the targeted NPs can be challenging, since it will be a mixture of encapsulated and released drug in plasma, tumors, and other tissues [47].…”

Section: Discussionmentioning

confidence: 99%

Targeted drug distribution in tumor extracellular fluid of GD2-expressing neuroblastoma patient-derived xenografts using SN-38-loaded nanoparticles conjugated to the monoclonal antibody 3F8

Monterrubio

Paco

Olaciregui

et al. 2017

Journal of Controlled Release

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Neuroblastoma is a pediatric solid tumor with high expression of the tumor associated antigen disialoganglioside GD2. Despite initial response to induction therapy, nearly 50% of high-risk neuroblastomas recur because of chemoresistance. Here we encapsulated the topoisomerase-I inhibitor SN-38 in polymeric nanoparticles (NPs) surface-decorated with the anti-GD2 mouse mAb 3F8 at a mean density of seven antibody molecules per NP. The accumulation of drug-loaded NPs targeted with 3F8 versus with control antibody was monitored by microdialysis in patient-derived GD2-expressing neuroblastoma xenografts. We showed that the extent of tumor penetration by SN-38 was significantly higher in mice receiving the targeted nano-drug delivery system when compared to non-targeted system or free drug. This selective penetration of the tumor extracellular fluid translated into a strong anti-tumor effect prolonging survival of mice bearing GD2-high neuroblastomas in vivo.

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“…Also, taste-masked melt-in-mouth formulation will avoid the reflex action (unlike other solid oral dosage forms which eventually might triggers vomiting) in paediatrics (29)(30)(31).…”

Section: Sensory Evaluation For Taste Masking and In Vivo Disintegratmentioning

confidence: 99%

Melt-in-Mouth Multi-particulate System for the Treatment of ADHD: A Convenient Platform for Pediatric Use

2015

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Abstract. Generally, pellets obtained from extrusion/spheronization, containing microcrystalline cellulose (MCC), do not disintegrate. An attempt has been made to develop melt-in-mouth pellets of taste-masked atomoxetine hydrochloride, using extrusion-spheronization, for pediatric patients. Melt-in-mouth pellets were prepared using extrusion-spheronization method and optimized using 3 3 FFD. MCC (X 1 , %), mannitol (X 2 , %) and Indion 414: Pharmaburst 500 ratio (X 3 , ratio) were the factors (independent variables) studied, whereas responses studied (dependent variables) were friability (Y1, %), yield (Y2, %) shape (Y3, roundness) in vitro disintegration time (Y4, seconds). The optimized formulation obtained from FFD was characterized for friability, shape and morphology, in vitro disintegration time, porosity, moisture uptake, in vitro release study and in vivo taste and disintegration time in healthy human volunteers. Randomized, two-treatment, two-sequence, two-period, single dose, crossover sensory evaluation study of taste-masked melt-in-mouth pellet was carried out in 10 healthy human subjects. A statistically significant polynomial mathematical relationship was generated between the factors and responses to obtain an optimized formulation. The optimized formulation was characterized (in vitro and in vivo) and exhibited a rapid drug release in vitro attributed to fast disintegration of pellets and high solubility of drug in 0.1 N HCl and buffer (pH 6.8). In vivo, 40% of volunteers ranked taste-masked optimized formulation as slightly bitter while 60% ranked it as no taste. The optimized pellets were conveniently administered in volunteers and exhibited rapid in-vivo disintegration in the oral cavity. Melt-in-mouth pellets can be a used as a platform technology for administering drugs to paediatric patients accurately and conveniently resulting in patient compliance.

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Nanomedicines in the future of pediatric therapy

Cited by 53 publications

References 237 publications

Novel Poly(Ethylene Oxide)-b-Poly(Propylene Oxide) Copolymer-Glucose Conjugate by the Microwave-Assisted Ring Opening of a Sugar Lactone

Novel Poly(Ethylene Oxide)-b-Poly(Propylene Oxide) Copolymer-Glucose Conjugate by the Microwave-Assisted Ring Opening of a Sugar Lactone

Targeted drug distribution in tumor extracellular fluid of GD2-expressing neuroblastoma patient-derived xenografts using SN-38-loaded nanoparticles conjugated to the monoclonal antibody 3F8

Melt-in-Mouth Multi-particulate System for the Treatment of ADHD: A Convenient Platform for Pediatric Use

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