Preparation, characterization and nasal delivery of α-cobrotoxin-loaded poly(lactide-co-glycolide)/polyanhydride microspheres

Li, Y.; Jiang, Hongliang; Zhu, Kan; Liu, J.H.; Hao, Yu-jie

doi:10.1016/j.jconrel.2005.07.007

Cited by 19 publications

(11 citation statements)

References 32 publications

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“…Based on DLS measurement, the diameter of PLGA50-6.5K NS and PLGA 85-142K NS was 400 nm and 890 nm respectively in aqueous solution, possibly due to some degree of swelling or/and certain discrepancy between the two different methods. The changes in size and shape of similar PLGA spheres in aqueous solution over long-term culture were reported previously by our lab [40] and others [37]. Such PLGA spheres swelled first and then deformed from their original spherical shape into irregular shape with a rough surface texture over time.…”

Section: Resultssupporting

confidence: 74%

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Novel antibacterial nanofibrous PLLA scaffolds

Feng

Sun

Bradley

et al. 2010

Journal of Controlled Release

126

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In order to achieve high local bioactivity and low systemic side effects of antibiotics in the treatment of dental, periodontal and bone infections, a localized and temporally controlled delivery system is crucial. In this study, a three-dimensional (3D) porous tissue engineering scaffold was developed with the ability to release antibiotics in a controlled fashion for long-term inhibition of bacterial growth. The highly soluble antibiotic drug, Doxycycline (DOXY), was successfully incorporated into PLGA nanospheres using a modified water-in-oil-in-oil (w/o/o) emulsion method. The PLGA nanospheres (NS) were then incorporated into prefabricated nanofibrous PLLA scaffolds with a well interconnected macroporous structure. The release kinetics of DOXY from four different PLGA NS formulations on a PLLA scaffold was investigated. DOXY could be released from the NS-scaffolds in a locally and temporally controlled manner. The DOXY release is controlled by DOXY diffusion out of the NS and is strongly dependent upon the physical and chemical properties of the PLGA. While PLGA50-6.5K, PLGA50-64K, and PLGA75-113K NSscaffolds discharge DOXY rapidly with a high initial burst release, PLGA85-142K NS-scaffold can extend the release of DOXY to longer than 6 weeks with a low initial burst release. Compared to NS alone, the NS incorporated on a 3-D scaffold had significantly reduced the initial burst release. In vitro antibacterial tests of PLGA85 NS-scaffold demonstrated its ability to inhibit common bacterial growth (S.aureus and E.coli) for a prolonged duration. The successful incorporation of DOXY onto 3-D scaffolds and its controlled release from scaffolds extends the usage of nano-fibrous scaffolds from the delivery of large molecules such as growth factors to the delivery of small hydrophilic drugs, allowing for a broader application and a more complex tissue engineering strategy.

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Section: Resultssupporting

confidence: 74%

“…[37, 38] Briefly, 80 mg PLGA was dissolved in 1 ml solvent mixture of acetonitrile/DMC (3:2 in volume ratio). 100 μl aqueous solution of certain amount of DOXY was added into the above solution and emulsified with a probe sonicator at 50 W (Virsonic 100, Gardiner, NY).…”

Section: Methodsmentioning

confidence: 99%

Novel antibacterial nanofibrous PLLA scaffolds

Feng

Sun

Bradley

et al. 2010

Journal of Controlled Release

126

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“…Microspheres provide an effective means of protecting, releasing and potentially targeting drugs for various biomedical applications. Drugcarrying microspheres have been administered in animals and humans via intravascular (4), inhalation (5), nasal (6), subcutaneous (7) and other routes. Regardless of the route of administration, microspheres are eventually cleared from the body by phagocytosis, which is one of the body's innate modes of defense against invading pathogens and other nonindigenous particulate matter (8).…”

Section: Introductionmentioning

confidence: 99%

Role of Particle Size in Phagocytosis of Polymeric Microspheres

2008

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Purpose-Polymeric microspheres are extensively researched for applications in drug and vaccine delivery. However, upon administration into the body, microspheres are primarily cleared via phagocytosis by macrophages. Although numerous studies have reported on the biochemical pathways of phagocytosis, relatively little is known about the dependence of phagocytosis on particle size. Here, we investigate the previously unexplained dependence of phagocytosis on particle size.Methods-Rat alveolar macrophages and IgG-opsonized and non-opsonized polystyrene microspheres were used as model macrophages and drug delivery particles. Phagocytosis, attachment and internalization were measured by flow cytometry and time-lapse video microscopy.Results-Particles possessing diameters of 2-3 μm exhibited maximal phagocytosis and attachment. Rate of internalization, however, was not affected significantly by particle size. Maximal attachment of 2-3 μm microspheres is hypothesized to originate from the characteristic features of membrane ruffles in macrophages. Elimination of ruffles via osmotic swelling nearly eliminated the peculiar size-dependence of phagocytosis. A simple mathematical model is presented to describe the dependence of phagocytosis on particle size.Conclusions-The dependence of phagocytosis on particle size originated primarily from the attachment step. These results reveal the importance of controlling drug delivery particle size distribution and selecting the size appropriate for avoiding or encouraging phagocytosis.

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“…Such a compound can be, for example, phospholipase A2 (PLA2). There are several publication concerning the in vivo central effects of post-synaptic -neurotoxins [17][18][19][20][21]. However, only 0.2% of the amount injected can reach the brain.…”

Section: Interacting With Cns or Its Structures In Vivo A) Effects Ofmentioning

confidence: 99%

Effects of Snake Venom Polypeptides on Central Nervous System

Osipov¹,

Utkin²

2012

CNSAMC

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The nervous system is a primary target for animal venoms as the impairment of its function results in the fast and efficient immobilization or death of a prey. There are numerous evidences about effects of crude snake venoms or isolated toxins on peripheral nervous system. However, the data on their interactions with the central nervous system (CNS) are not abundant, as the blood-brain barrier (BBB) impedes penetration of these compounds into brain. This updated review presents the data about interaction of snake venom polypeptides with CNS. Such data will be described according to three main modes of interactions: - Direct in vivo interaction of CNS with venom polypeptides either capable to penetrate BBB or injected into the brain. - In vitro interactions of cell or sub-cellular fractions of CNS with crude venoms or purified toxins. - Indirect effects of snake venoms or their components on functioning of CNS under different conditions. Although the venom components penetrating BBB are not numerous, they seem to be the most suitable candidates for the leads in drug design. The compounds with other modes of action are more abundant and better studied, but the lack of the data about their ability to penetrate BBB may substantially aggravate the potentials for their medical perspectives. Nevertheless, many such compounds are used for research of CNS in vitro. These investigations may give invaluable information for understanding the molecular basis of CNS diseases and thus lay the basis for targeted drug design. This aspect also will be outlined in the review.

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Preparation, characterization and nasal delivery of α-cobrotoxin-loaded poly(lactide-co-glycolide)/polyanhydride microspheres

Cited by 19 publications

References 32 publications

Novel antibacterial nanofibrous PLLA scaffolds

Novel antibacterial nanofibrous PLLA scaffolds

Role of Particle Size in Phagocytosis of Polymeric Microspheres

Effects of Snake Venom Polypeptides on Central Nervous System

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