Triggered destabilisation of polymeric micelles and vesicles by changing polymers polarity: An attractive tool for drug delivery

Rijcken, Cristianne J.F.; Soga, Osamu; Hennink, Wim E.; Nostrum, Cornelus F. van

doi:10.1016/j.jconrel.2007.03.023

Cited by 456 publications

(458 citation statements)

References 184 publications

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“…0.05) from that observed in the prelyophilization process (20.45 ± 1.65), indicating formation of SSMs with a typical particle size of polymeric micelles between 10 and 100 nm. 35 Due to their small size, the likelihood that BUD-SSMs would undergo phagocytosis in the alveoli is much lower than that for micron-sized particles, because it has been reported that particles of less than 260 nm can escape phagocytosis by macrophages. 36 The zeta potential measurement gives an indication of the stability of the colloidal system.…”

Section: Drug Loading and Maximum Solubilitymentioning

confidence: 99%

Rehydrated sterically stabilized phospholipid nanomicelles of budesonide for nebulization: physicochemical characterization and in vitro, in vivo evaluations

Sahib¹,

Darwis²,

Peh³

et al. 2011

IJN

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Background: Inhaled corticosteroids provide unique systems for local treatment of asthma or chronic obstructive pulmonary disease. However, the use of poorly soluble drugs for nebulization has been inadequate, and many patients rely on large doses to achieve optimal control of their disease. Theoretically, nanotechnology with a sustained-release formulation may provide a favorable therapeutic index. The aim of this study was to determine the feasibility of using sterically stabilized phospholipid nanomicelles of budesonide for pulmonary delivery via nebulization. Methods: PEG 5000 -DSPE polymeric micelles containing budesonide (BUD-SSMs) were prepared by the coprecipitation and reconstitution method, and the physicochemical and pharmacodynamic characteristics of BUD-SSMs were investigated. Results: The optimal concentration of solubilized budesonide at 5 mM PEG 5000 -DSPE was 605.71 ± 6.38 µg/mL, with a single-sized peak population determined by photon correlation spectroscopy and a particle size distribution of 21.51 ± 1.5 nm. The zeta potential of BUD-SSMs was −28.43 ± 1.98 mV. The percent entrapment efficiency, percent yield, and percent drug loading of the lyophilized formulations were 100.13% ± 1.09%, 97.98% ± 1.95%, and 2.01% ± 0.02%, respectively. Budesonide was found to be amorphous by differential scanning calorimetry, and had no chemical interaction with PEGylated polymer according to Fourier transform infrared spectroscopy. Transmission electron microscopic images of BUD-SSMs revealed spherical nanoparticles. BUD-SSMs exhibited prolonged dissolution behavior compared with Pulmicort Respules ® (P , 0.05). Aerodynamic characteristics indicated significantly higher deposition in the lungs compared with Pulmicort Respules ® . The mass median aerodynamic, geometric standard deviation, percent emitted dose, and the fine particle fraction were 2.83 ± 0.08 µm, 2.33 ± 0.04 µm, 59.13% ± 0.19%, and 52.31% ± 0.25%, respectively. Intratracheal administration of BUD-SSMs 23 hours before challenge (1 mg/kg) in an asthmatic/chronic obstructive pulmonary disease rat model led to a significant reduction in inflammatory cell counts (76.94 ± 5.11) in bronchoalveolar lavage fluid compared with administration of Pulmicort Respules ® (25.06 ± 6.91). Conclusion:The BUD-SSMs system might be advantageous for asthma or chronic obstructive pulmonary disease and other inflammatory airway diseases.

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Section: Drug Loading and Maximum Solubilitymentioning

confidence: 99%

Rehydrated sterically stabilized phospholipid nanomicelles of budesonide for nebulization: physicochemical characterization and in vitro, in vivo evaluations

Sahib¹,

Darwis²,

Peh³

et al. 2011

IJN

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“…Light in the ultraviolet (UV), visible (VIS) or near-infrared (NIR) region has been applied as the trigger [41]; however, since NIR light penetrates deeper into tissues and induces minimal damage to healthy cells, it is of particular interest for biomedical applications [42]. Jiang et al reported a PEG-b-poly(2-nitrobenzyl methacrylate) system [43] where the cleavage of 2-nitrobenzyl moieties occurred by photolysis either via one photon UV (365 nm) or two-photon NIR (700 nm) excitation.…”

Section: Exogenous Triggersmentioning

confidence: 99%

Multifunctional nanoassemblies of block copolymers for future cancer therapy

Cabral

Kataoka

2010

Science and Technology of Advanced Materials

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Nanoassemblies from amphiphilic block copolymers are promising nanomedicine platforms for cancer diagnosis and therapy due to their relatively small size, high loading capacity of drugs, controlled drug release, in vivo stability and prolonged blood circulation. Recent clinical trials with self-assembled polymeric micelles incorporating anticancer drugs have shown improved antitumor activity and decreased side effects encouraging the further development of nanoassemblies for drug delivery. This review summarizes recent approaches considering stimuli-responsive, multifunctionality and more advanced architectures, such as vesicles or worm-like micelles, for tumor-specific drug and gene delivery.

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“…For the mixed system, eq. 5 can be expressed as: (6) where C is the total mixed polymer concentration; x i is the weight fraction of hydrophobic blocks in each polymer and ρ i (i=PLLA, PH) is the density of the hydrophobic blocks in each polymer, which is assumed to be the value of bulk poly(L-Lactide) (1.25 g.cm −3 ) [24] and poly (L-Histidine) (1.44 g.cm −3 ) [25] respectively. From the slope of the graph in Figure 3.b, the K v value of the system was determined to be 2.4×10 4 .…”

Section: Physicochemical Properties Of the Mixed Micelles At Ph 74mentioning

confidence: 99%

“…In recent years, polymeric micelles have been extensively investigated for pharmaceutical applications because of their attractive features as drug delivery vehicles [1][2][3][4][5][6]. Polymeric micelles mimic aspects of the biological transport system in terms of structure and function.…”

Section: Introductionmentioning

confidence: 99%

Physicochemical characteristics of pH-sensitive poly(l-Histidine)-b-poly(ethylene glycol)/poly(l-Lactide)-b-poly(ethylene glycol) mixed micelles

Yin

Lee

Kim

et al. 2008

Journal of Controlled Release

155

110

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A novel pH-sensitive polymeric micellar system composed of poly(L-Histidine)-b-poly(ethylene glycol) and poly(L-Lactide)-b-poly(ethylene glycol) block copolymers was studied by dynamic/static light scattering, spectrofluorimetry and differential scanning calorimetry. The mixed micelles displayed ultra pH sensitivity which could be tuned by varying the mixing ratio of the two polymers. In particular, mixed micelles composed of 25 wt. % poly(L-Lactide)-b-poly(ethylene glycol) exhibited desirable pH dependency which could be used as a drug delivery system that selectively targeted the extracellular pH of acidic solid tumors. Micelles were quite stable from pH 7.4 to 7.0 but underwent a two-stage destabilization as pH decreased further. A significant increase in size and aggregation number was observed when pH dropped to 6.8. Further disruption of the micelle core eventually caused phase separation in the micelle core and dissociation of ionized poly(L-Histidine)-b-poly (ethylene glycol) molecules from the micelles as pH decreased to 6.0. Increased electrostatic repulsions which arise from the progressive protonation of imidazole rings overwhelming the hydrophobic interactions among uncharged neutral blocks is considered to be the mechanism for destabilization of the micelle core.

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Triggered destabilisation of polymeric micelles and vesicles by changing polymers polarity: An attractive tool for drug delivery

Cited by 456 publications

References 184 publications

Rehydrated sterically stabilized phospholipid nanomicelles of budesonide for nebulization: physicochemical characterization and in vitro, in vivo evaluations

Rehydrated sterically stabilized phospholipid nanomicelles of budesonide for nebulization: physicochemical characterization and in vitro, in vivo evaluations

Multifunctional nanoassemblies of block copolymers for future cancer therapy

Physicochemical characteristics of pH-sensitive poly(l-Histidine)-b-poly(ethylene glycol)/poly(l-Lactide)-b-poly(ethylene glycol) mixed micelles

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