Efavirenz-Loaded Polymeric Micelles for Pediatric Anti-HIV Pharmacotherapy with Significantly Higher Oral Bioavailability

Chiappetta, Diego Andrés; Höcht, Christián; Taira, Carlos A.; Sosnik, Alejandro

doi:10.2217/nnm.09.90

Cited by 156 publications

(129 citation statements)

References 49 publications

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“…These two premises were taken into account when choosing the poloxamine varieties included in the study. Our hypothesis was that co-micellization of T1107 and T1307 with the more hydrophobic derivative T904 would lead to the large encapsulation extents characteristic of T904 and, at the same time, obtain drug-loaded micelles with improved physical stability compared with those of T904 [35,36]. Poloxamine was previously mixed with poloxamer to enhance the physical stability of efavirenz-loaded micelles [27].…”

Section: Self-aggregation Of Poloxaminesmentioning

confidence: 99%

Single and mixed poloxamine micelles as nanocarriers for solubilization and sustained release of ethoxzolamide for topical glaucoma therapy

Ribeiro

Sosnik

Chiappetta

et al. 2012

J. R. Soc. Interface.

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Polymeric micelles of single and mixed poloxamines (Tetronic) were evaluated regarding their ability to host the antiglaucoma agent ethoxzolamide (ETOX) for topical ocular application. Three highly hydrophilic varieties of poloxamine (T908, T1107 and T1307) and a medium hydrophilic variety (T904), possessing a similar number of propylene oxide units but different contents in ethylene oxide, were chosen for the study. The critical micellar concentration and the cloud point of mixed micelles in 0.9 per cent NaCl were slightly greater than the values predicted from the additive rule, suggesting that the co-micellization is hindered. Micellar size ranged between 17 and 120 nm and it was not altered after the loading of ETOX (2.7-11.5 mg drug g -1 poloxamine). Drug solubilization ability ranked in the order: T904 (50-fold increase in the apparent solubility) . T1107 ffi T1307 . T908. Mixed micelles showed an intermediate capability to host ETOX but a greater physical stability, maintaining almost 100 per cent drug solubilized after 28 days. Furthermore, the different structural features of poloxamines and their combination in mixed micelles enabled the tuning of drug release profiles, sustaining the release in the 1-5 days range. These findings together with promising hen's egg test-chorioallantoic membrane biocompatibility tests make poloxamine micelles promising nanocarriers for carbonic anhydrase inhibitors in the treatment of glaucoma.

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Section: Self-aggregation Of Poloxaminesmentioning

confidence: 99%

Single and mixed poloxamine micelles as nanocarriers for solubilization and sustained release of ethoxzolamide for topical glaucoma therapy

Ribeiro

Sosnik

Chiappetta

et al. 2012

J. R. Soc. Interface.

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“…When micelles displaying totally amorphous cores (e.g. PEO-PPO) were employed for the encapsulation of antibacterial and antiretroviral agents [51][52][53], lyophilization/resuspension was possible without the addition of any additive; sizes and size distributions remained unchanged.…”

Section: Lyophilization Of Rif-loaded Micellesmentioning

confidence: 99%

Cryoprotection–lyophilization and physical stabilization of rifampicin-loaded flower-like polymeric micelles

Morettón

Chiappetta

Sosnik

2011

J. R. Soc. Interface.

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Rifampicin-loadedpoly(e-caprolactone)-b-poly(ethylene glycol) -poly(e-caprolactone) flower-like polymeric micelles display low aqueous physical stability over time and undergo substantial secondary aggregation. To improve their physical stability, the lyoprotectionlyophilization process was thoroughly characterized. The preliminary cryoprotectant performance of mono-and disaccharides (e.g. maltose, glucose), hydroxypropyl-bcyclodextrin (HPbCD) and poly(ethylene glycol) (PEG) of different molecular weights was assessed in freeze -thawing assays at 2208C, 2808C and 21968C. The size and size distribution of the micelles at the different stages were measured by dynamic light scattering (DLS). A cryoprotectant factor ( f c ) was determined by taking the ratio between the size immediately after the addition of the cryoprotectant and the size after the preliminary freeze -thawing assay. The benefit of a synergistic cryoprotection by means of saccharide/ PEG mixtures was also assessed. Glucose (1 : 20), maltose (1 : 20), HPbCD (1 : 5) and glucose or maltose mixtures with PEG3350 (1 : 20) (copolymer:cryoprotectant weight ratio) were the most effective systems to protect 1 per cent micellar systems. Conversely, only HPbCD (1 : 5) cryoprotected more concentrated drug-loaded micelles (4% and 6%). Then, those micelle/ cryoprotectant systems that displayed f c values smaller than 2 were freeze-dried. The morphology of freeze-dried powders was characterized by scanning electron microscopy and atomic force microscopy and the residual water content analysed by the Karl Fisher method. The HPbCD-added lyophilisates were brittle porous cakes (residual water was between 0.8% and 3%), easily redispersable in water to form transparent systems with a minimal increase in the micellar size, as determined by DLS.

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“…Poly(ethylene oxide)-poly(propylene oxide) Efavirenz (EFV) [48] In vitro, Protective effect against intestine-mimicking.…”

Section: Block Copolymer Micellesmentioning

confidence: 99%

Functionalized Polymers for Enhance Oral Bioavailability of Sensitive Molecules

et al. 2016

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Currently, many sensitive molecules have been studied for effective oral administration. These substances are biologically active compounds that mainly suffer early degradation in the gastrointestinal tract (GIT) and physicochemical instability, inactivation and poor solubility and permeability. The sensibility of the biomolecules has limited their oral administration in the body and today is an important research topic to achieve desired effects in medicine field. Under this perspective, various enhancement approaches have been studied as alternatives to increase their oral bioavailability. Some of these strategies include functionalized polymers to provide specific useful benefits as protection to the intestinal tract by preventing its degradation by stomach enzymes, to increase their absorption, permeability, stability, and to make a proper release in the GIT. Due to specific chemical groups, shapes and sizes, morphologies, mechanical properties, and degradation, recent advances in functionalized polymers have opened the door to great possibilities to improve the physicochemical characteristics of these biopharmaceuticals. Today, many biomolecules are found in basic studies, preclinical steps, and others are late stage clinical development. This review summarizes the contribution of functionalized polymers to enhance oral bioavailability of sensitive molecules and their application status in medicine for different diseases. Future trends of these polymers and their possible uses to achieve different formulation goals for oral delivery are also covered in this manuscript.

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Efavirenz-Loaded Polymeric Micelles for Pediatric Anti-HIV Pharmacotherapy with Significantly Higher Oral Bioavailability

Abstract: This strategy appears a very promising one towards the development of a liquid aqueous EFV formulation for the improved pediatric HIV pharmacotherapy.

Cited by 156 publications

References 49 publications

Single and mixed poloxamine micelles as nanocarriers for solubilization and sustained release of ethoxzolamide for topical glaucoma therapy

Single and mixed poloxamine micelles as nanocarriers for solubilization and sustained release of ethoxzolamide for topical glaucoma therapy

Cryoprotection–lyophilization and physical stabilization of rifampicin-loaded flower-like polymeric micelles

Functionalized Polymers for Enhance Oral Bioavailability of Sensitive Molecules

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