Nanoengineered Particles for Enhanced Intra‐Articular Retention and Delivery of Proteins

Singh, Ankur; Agarwal, Rachit; Diaz-Ruiz, Carlos A.; Willett, Nick J.; Wang, Peiyi; Lee, L. Andrew; Wang, Qian; Guldberg, Robert E.; Garcı́a, Andrés J.

doi:10.1002/adhm.201400051

Cited by 59 publications

(77 citation statements)

References 32 publications

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“…These needles have a diameter of 0.84 mm-0.21 mm respectively and that is why the average particle size has to be small enough not to clog the needles. Since Singh et al 26 applied nanoengineered particles with average particle size of 303±13 nm and 500±22 nm intraarticularly via 27G needle without any clogging problem, the hydrogel formulation bearing F6 coded nanoparticle with 190.8±3.1 nm average particle size may be applied via syringe equipped with 18G or 27G needle in the present study.…”

Section: Resultsmentioning

confidence: 99%

<i>In Situ</i> Hydrogel Formulation for Intra-Articular Application of Diclofenac Sodium-Loaded Polymeric Nanoparticles

Küçüktürkmen

Öz

Bozkır

2017

tjps

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Objectives: The world's population is getting older and the number of people suffering from arthritis is a major problem according to World Health Organization's data. In this respect, the need for more efficient treatment for arthritis becomes an urgent issue. In this research, nanoparticle bearing in situ gelling hydrogel formulation was developed for prolonged local delivery of diclofenac sodium (DS). Materials and Methods: Emulsion-solvent evaporation technique was used for the preparation of nanoparticles. Particle size, encapsulation efficiency, morphology, and drug release profile of DS loaded biodegradable nanoparticles as well as gel viscosity and gelation time of in situ gelling hydrogel formulations were optimized to increase the time interval between each dose application for enhanced patience compliance. Results:The spherical nanoparticles with a mean particle diameter of 168 nm was obtained and confirmed by both transmission electron microscope and atomic force microscope. Different types of surfactants were tested in the first emulsification step of nanoparticle production process and Arlacel ® -C significantly increased the encapsulation efficiency to 89.7%. Thirty days prolonged in vitro release of DS was achieved by using the combined formulation of polymeric nanoparticles and in situ hydrogel prepared by using poloxomer 407 and chitosan. Conclusion: Local administration of DS with this novel delivery system could be considered of having potential to minimize side effects associated with decreased amount of drug in dosage form compared to conventional oral dose. Key words: Diclofenac sodium, drug delivery, PLGA, Poly(ε-caprolactone), thermosensitive hydrogel, poloxamers ABSTRACT ÖZ Amaç: Dünya Sağlık Örgütü'nün verilerine göre dünya çapında insanların yaş ortalaması ve bağlantılı olarak artrit hastalığından mağdur olan insan sayısı da artmaktadır. Bu açıdan bakıldığında, artrit tedavisi için daha etkili tedavilerin gerekliliği önemli hale gelmiştir. Bu araştırmada, diklofenak sodyumun (DS) uzatılmış lokal taşınımı için nanopartikül içeren in situ hidrojel formülasyonları geliştirilmiştir. Gereç ve Yöntemler: Nanopartiküllerin hazırlanmasında emülsiyon-çözücü buharlaştırma yöntemi kullanılmıştır. DS yüklü nanopartiküllerin partikül büyüklüğü, enkapsülasyon etkinliği, morfolojisi ve ilaç salım profilleri ile in situ hidrojelin jel viskozitesi ve jelleşme süresi, hasta uyuncunu artırmak için her bir dozun uygulanması arasındaki zamanı artırmak amacıyla optimize edilmiştir. Bulgular: Ortalama partikül büyüklüğü 168 nm olan küresel nanopartiküller elde edilmiş ve geçirimli elektron mikroskobu ve atomik kuvvet mikroskobu ile desteklenmiştir. Nanopartikül üretim sürecinin ilk emülsifikasyon adımında farklı sürfaktanlar denenmiş ve Arlacel ® -C diklofenak sodyumun enkapsülasyon etkinliğini %89.7'ye yükseltmiştir. DS'nin 30 güne uzatılmış in vitro salımı, nanopartiküllerin ve poloksamer 407/kitozan ile hazırlanmış in situ hidrojelin kombine kullanılmasıyla başarılmıştır. Sonuç: DS'nin bu yenilikçi taşıy...

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Section: Resultsmentioning

confidence: 99%

<i>In Situ</i> Hydrogel Formulation for Intra-Articular Application of Diclofenac Sodium-Loaded Polymeric Nanoparticles

Küçüktürkmen

Öz

Bozkır

2017

tjps

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“…These particles also demonstrated increased retention time in the articular space with a half-life of 3.01 ± 0.09 days for IL1Ra particles compared to 0.96 ± 0.08 days for soluble IL1Ra (Figure 2B). Follow-up work by the same research group demonstrated that modulation of the size of the particle from 500 nm to 900 nm using a poly-hydroxyethylmethacrylate (pHEMA) backbone functionalized with hydrophobic pyridine side chains increased average particle retention time in the knee joint (Figure 2C–D) [25]. The pHEMA particles were then used in an in vitro setting with IL1Ra, and it was demonstrated that cells treated with IL1β and exposed to IL1Ra nanoparticles maintained NF-κB expression levels similar to those of unstimulated controls, demonstrating protection [26].…”

Section: Low Complexity: Single Cytokine Interventionsmentioning

confidence: 99%

“…In a subsequent study 900 nm particles were developed (C) which maintained bioactivity while increasing total signal retention in the knee as measured by near-infrared fluorescent signal intensity (D). Reproduced with permission from references [24] (A–B), [26] (C), and [25] (D).…”

Section: Figurementioning

confidence: 99%

Biomaterial strategies for generating therapeutic immune responses

Kelly

Shores

Votaw

et al. 2017

Advanced Drug Delivery Reviews

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Biomaterials employed to raise therapeutic immune responses have become a complex and active field. Historically, vaccines have been developed primarily to fight infectious diseases, but recent years have seen the development of immunologically active biomaterials towards an expanding list of non-infectious diseases and conditions including inflammation, autoimmunity, wounds, cancer, and others. This review structures its discussion of these approaches around a progression from single-target strategies to those that engage increasingly complex and multifactorial immune responses. First the targeting of specific individual cytokines is discussed, both in terms of delivering the cytokines or blocking agents, and in terms of active immunotherapies that raise neutralizing immune responses against such single cytokine targets. Next, non-biological complex drugs such as randomized polyamino acid copolymers are discussed in terms of their ability to raise multiple different therapeutic immune responses, particularly in the context of autoimmunity. Last, biologically derived matrices and materials are discussed in terms of their ability to raise complex immune responses in the context of tissue repair. Collectively, these examples reflect the tremendous diversity of existing approaches and the breadth of opportunities that remain for generating therapeutic immune responses using biomaterials.

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“…This study showed that IL-1Ra NPs are indeed capable of blocking IL-1β activity in response to NF-κβ signaling activation in vitro . In another study, Singh et al 86 engineered nanoparticles made of PHEMA modified with hydrophobic pyridine (Figure 4B). The unique hydrophilic/hydrophobic balance of properties of the polymer allowed for precise control of the size of NPs in the 300-900 nm range and demonstrated a size dependent retention of protein-nanoparticle in a healthy rat knee joint with 900 nm protein particles localized to the knee for at least 14 days compared to depletion of bolus protein within hours of injection.…”

Section: Drugs That Inhibit Inflammationmentioning

confidence: 99%

“…VivoTag-S 750-BSA-particles with 900 nm size show sustained signal compared to 500 nm nanoparticles and soluble BSA. Reproduced with permission 86,40 .…”

Section: Figurementioning

confidence: 99%

Osteoarthritis: Pathology, Mouse Models, and Nanoparticle Injectable Systems for Targeted Treatment

et al. 2016

Self Cite

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Osteoarthritis (OA) is a progressive, degenerative disease of articulating joints that not only affects the elderly, but also involves younger, more active individuals with prolonged participation in high physical-demand activities. Thus, effective therapies that are easy to adopt clinically are critical in limiting the societal burden associated with OA. This review is focused on intra-articular injectable regimens and provides a comprehensive look at existing in vivo models of OA that might be suitable for developing, testing, and finding a cure for OA by intra-articular injections. We first discuss the pathology, molecular mechanisms responsible for the initiation and progression of OA, and challenges associated with disease-specific targeting of OA. We proceed to discuss available animal models of OA and provide a detailed perspective on the use of mouse models in studies of experimental OA. We finally provide a closer look at intra-articular injectable treatments for OA, focusing on biomaterials-based nanoparticles, and provide a comprehensive overview of the various nanometer-size ranges studied.

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Nanoengineered Particles for Enhanced Intra‐Articular Retention and Delivery of Proteins

Cited by 59 publications

References 32 publications

<i>In Situ</i> Hydrogel Formulation for Intra-Articular Application of Diclofenac Sodium-Loaded Polymeric Nanoparticles

<i>In Situ</i> Hydrogel Formulation for Intra-Articular Application of Diclofenac Sodium-Loaded Polymeric Nanoparticles

Biomaterial strategies for generating therapeutic immune responses

Osteoarthritis: Pathology, Mouse Models, and Nanoparticle Injectable Systems for Targeted Treatment

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