New polymeric carriers for controlled drug delivery following inhalation or injection

Fu, Jie; Fiegel, Jennifer; Krauland, Eric; Hanes, Justin

doi:10.1016/s0142-9612(02)00182-5

Cited by 157 publications

(126 citation statements)

References 37 publications

Supporting

Mentioning

123

Contrasting

Unclassified

Order By: Relevance

“…It is noteworthy that particles composed of random copolymers of PSA and PEG, the subject of previous reports by our group (37,38), were strongly immobilized in human mucus, likely due to insufficient freedom of the PEG chains to partition to the particle surface when they are flanked on both ends by PSA segments (i.e., PSA-PEG-PSA random copolymers versus the PSA-PEG diblock copolymers used here). Recently, PEGylated PLGA nanoparticles, formed by adsorbing avidin-palmitic acid to the surface of PLGA nanoparticles and subsequently attaching biotin-PEG, exhibited a 2-to 10-fold improvement in particle penetration speed in ovulatory endocervical mucus (OCM) compared to uncoated particles (15).…”

Section: Discussionmentioning

confidence: 74%

See 1 more Smart Citation

Biodegradable polymer nanoparticles that rapidly penetrate the human mucus barrier

Tang¹,

Dawson²,

Lai

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

403

289

View full text Add to dashboard Cite

Protective mucus coatings typically trap and rapidly remove foreign particles from the eyes, gastrointestinal tract, airways, nasopharynx, and female reproductive tract, thereby strongly limiting opportunities for controlled drug delivery at mucosal surfaces. No synthetic drug delivery system composed of biodegradable polymers has been shown to penetrate highly viscoelastic human mucus, such as non-ovulatory cervicovaginal mucus, at a significant rate. We prepared nanoparticles composed of a biodegradable diblock copolymer of poly(sebacic acid) and poly(ethylene glycol) (PSA-PEG), both of which are routinely used in humans. In fresh undiluted human cervicovaginal mucus (CVM), which has a bulk viscosity approximately 1,800-fold higher than water at low shear, PSA-PEG nanoparticles diffused at an average speed only 12-fold lower than the same particles in pure water. In contrast, similarly sized biodegradable nanoparticles composed of PSA or poly(lacticco-glycolic acid) (PLGA) diffused at least 3,300-fold slower in CVM than in water. PSA-PEG particles also rapidly penetrated sputum expectorated from the lungs of patients with cystic fibrosis, a disease characterized by hyperviscoelastic mucus secretions. Rapid nanoparticle transport in mucus is made possible by the efficient partitioning of PEG to the particle surface during formulation. Biodegradable polymeric nanoparticles capable of overcoming human mucus barriers and providing sustained drug release open significant opportunities for improved drug and gene delivery at mucosal surfaces.cystic fibrosis ͉ drug delivery ͉ gene therapy ͉ mucosa ͉ mucus-penetrating particle

show abstract

Section: Discussionmentioning

confidence: 74%

“…Sebacic anhydride (Acyl-SA) was prepared as previously described (38). Polyethylene glycol methyl ether (M W 5,000 Da, mPEG, Sigma) was dried under vacuum to constant weight.…”

Section: Methodsmentioning

confidence: 99%

Biodegradable polymer nanoparticles that rapidly penetrate the human mucus barrier

Tang¹,

Dawson²,

Lai

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

403

289

View full text Add to dashboard Cite

show abstract

“…In addition, distributions that include a wide range of both large and small particle sizes have shown a lack of control in depositing the drug at the specific sites of infection [13]. To deal with these problems, recent work has focused on "large porous" particles exhibiting geometric diameters larger than 10 μm but with aerodynamic diameters of ∼1-3 μm [14][15][16][17]. Large porous particles exhibit the aerodynamics of smaller particles while maintaining a size large enough to resist uptake by alveolar macrophages [18]; however, a narrow aerodynamic diameter is still desired.…”

Section: Introductionmentioning

confidence: 99%

NanoCipro encapsulation in monodisperse large porous PLGA microparticles

Arnold

Gorman

Schieber

et al. 2007

Journal of Controlled Release

117

View full text Add to dashboard Cite

Pulmonary drug delivery of controlled release formulations may provide an effective adjunct approach to orally delivered antibiotics for clearing persistent lung infections. Dry powder formulations for this indication should possess characteristics including; effective deposition to infected lung compartments, persistence at the infection site, and steady release of antibiotic. Large porous particles (∼10-15 μm) have demonstrated effective lung deposition and enhanced lung residence as a result of their large diameter and reduced clearance by macrophages in comparison to small microparticles (∼1-5 μm). In this report, Precision Particle Fabrication technology was used to create monodisperse large porous particles of poly(D,L-lactic-co-glycolic acid) (PLGA) utilizing oils as extractable porogens. After extraction, the resulting large porous PLGA particles exhibited a low density and a web-like or hollow interior depending on porogen concentration and type, respectively. Ciprofloxacin nanoparticles (nanoCipro) created by homogenization in dichloromethane, possessed a polymorph with a decreased melting temperature. Encapsulating nanoCipro in large porous PLGA particles resulted in a steady release of ciprofloxacin that was extended for larger particle diameters and for the solid particle morphology in comparison to large porous particles. The encapsulation efficiency of nanoCipro was quite low and factors impacting the entrapment of nanoparticles during particle formation were elucidated. A dry powder formulation with the potential to control particle deposition and sustain release to the lung was developed and insight to improve nanoparticle encapsulation is discussed.

show abstract

“…Particles in the size range of 1-5 lm are typical of bacteria and are readily engulfed by phagocytosis; this obviously limits the bioavailability of any therapeutics for entry into the blood circulation. To overcome this issue, Edwards, Hanes, and coworkers (13) developed large porous particles (LPP) with a geometric diameter of d g 10 lm and also low density (q \ 0.1 g cm 23 ), which promoted deposition deep into the lung and also persisted there by delaying phagocytosis. Systemic absorption was enhanced and insulin delivery highlighted the ability to achieve desirable uptake and systemic effects.…”

Section: Inhalation Of Synthetic Particles For Deep Lung Depositionmentioning

confidence: 99%

“…Therefore, to protect from rapid clearance or degradation and achieve sustained release within the lung, encapsulation in nanoparticles or microparticles has been pursued. Synthetic and natural degradable polymers are common and include poly(lactic-co-glycolic) acid (PLGA) (23,24), poly(ethylene glycol)-block-poly(sebacic acid) (PEG-PSA) (25), and gelatin (26), as well as liposomal delivery systems (27,28). Controlled release of insulin from PLGA microparticles in streptozotocin-induced diabetic rat lung resulted in significant reduction of blood glucose at relatively low doses (29).…”

Section: Inhalation Of Synthetic Particles For Deep Lung Depositionmentioning

confidence: 99%

Lung vascular targeting through inhalation delivery: Insight from filamentous viruses and other shapes

Mahmud

Discher

2011

IUBMB Life

View full text Add to dashboard Cite

SummarySystemic delivery of therapeutic agents via inhalation of particulates remains an attractive, noninvasive means of administration due to the possibilities of high bioavailability and high patient compliance. Optimization of particle shapes and particle properties for deep lung deposition after inhalation continues to be one of the key challenges. Here, we review several aspects of nanoparticle design for deep lung deposition as well as the nature and extent of translocation through the air-blood barrier for local or systemic vascular targeting. We describe filamentous influenza virus in comparison to worm-like ''filomicelle'' polymers as one example of a nature inspired design. IUBMBIUBMB Life, 63(8): 607-612, 2011

show abstract

New polymeric carriers for controlled drug delivery following inhalation or injection

Cited by 157 publications

References 37 publications

Biodegradable polymer nanoparticles that rapidly penetrate the human mucus barrier

Biodegradable polymer nanoparticles that rapidly penetrate the human mucus barrier

NanoCipro encapsulation in monodisperse large porous PLGA microparticles

Lung vascular targeting through inhalation delivery: Insight from filamentous viruses and other shapes

Contact Info

Product

Resources

About