Enhanced stability of horseradish peroxidase encapsulated in acetalated dextran microparticles stored outside cold chain conditions

Kanthamneni, Naveen; Sharma, Sadhana; Meenach, Samantha A.; Billet, Beau; Zhao, Ji‐Cheng; Bachelder, Eric M.; Ainslie, Kristy M.

doi:10.1016/j.ijpharm.2012.04.043

Cited by 57 publications

(47 citation statements)

References 26 publications

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“…We have demonstrated that enzyme encapsulated within Ace-DEX MPs, illustrated stable activity across a broad range of temperatures inside and outside the cold chain, indicating enhanced cargo stability (Kanthamneni et al, 2012) which is needed in the desert and tropical regions where Leishmania is endemic (McDowell et al, 2011). Polyesters such as poly-lactic (co-glycolic) acid (PLGA) and polycaprolactone (PCL) do not retain their stability outside of the cold chain and thus have additional treatment costs for VL (Oyewumi et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Host-mediated Leishmania donovani treatment using AR-12 encapsulated in acetalated dextran microparticles

Collier

Peine

Gautam

et al. 2016

International Journal of Pharmaceutics

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Leishmaniasis is a disease caused by parasites of Leishmania sp., which effects nearly 12 million people worldwide and is associated with treatment complications due to widespread parasite resistance toward pathogen-directed therapeutics. The current treatments for visceral leishmaniasis (VL), the systemic form of the disease, involve pathogen-mediated drugs and have long treatment regimens, increasing the risk of forming resistant strains. One way to limit emergence of resistant pathogens is through the use of host-mediated therapeutics. The host-mediated therapeutic AR-12, which is FDA IND-approved for cancer treatment, has shown activity against a broad spectrum of intracellular pathogens; however, due to hydrophobicity and toxicity, it is difficult to reach therapeutic doses. We have formulated AR-12 into microparticles (AR-12/MPs) using the novel biodegradable polymer acetalated dextran (Ace-DEX) and used this formulation for the systemic treatment of VL. Treatment with AR-12/MPs significantly reduced liver, spleen, and bone marrow parasite loads in infected mice, while combinatorial therapies with amphotericin B had an even more significant effect. Overall, AR-12/MPs offer a unique, host-mediated therapy that could significantly reduce the emergence of drug resistance in the treatment of VL.

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Section: Introductionmentioning

confidence: 99%

Host-mediated Leishmania donovani treatment using AR-12 encapsulated in acetalated dextran microparticles

Collier

Peine

Gautam

et al. 2016

International Journal of Pharmaceutics

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“…liposomes) or by local activation of a pro-drug. [21] Nanoparticles designed for cancer therapy consist of various components, generally a nanocarrier and an active agent. [22] Drug-carrier nanoparticles are considered as submicroscopic colloidal systems that may act as drug vehicles, either as nanospheres (the matrix system in which the drug is dispersed) or nanocapsules (reservoirs in which the drug is confined in hydrophobic or hydrophilic core surrounded by a single polymeric membrane).…”

Section: Nanocariers For Anticancer Drugsmentioning

confidence: 99%

Nanocarrier drugs in the treatment of brain tumors

Černá¹,

Stiborová²,

Adam³

et al. 2016

JCMT

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Nanoparticle-mediated targeted delivery of drugs might significantly reduce the dosage and optimize their release properties, increase specificity and bioavailability, improve shelf life, and reduce toxicity. Some nanodrugs are able to overcome the blood-brain barrier that is an obstacle to treatment of brain tumors. Vessels in tumors have abnormal architecture and are highly permeable; moreover, tumors also have poor lymphatic drainage, allowing for accumulation of macromolecules greater than approximately 40 kDa within the tumor microenvironment. Nanoparticles exploit this feature, known as the enhanced permeability and retention effect, to target solid tumors. Active targeting, i.e. surface modification of nanoparticles, is a way to decrease uptake in normal tissue and increase accumulation in a tumor, and it usually involves targeting surface membrane proteins that are upregulated in cancer cells. The targeting molecules are typically antibodies or their fragments; aptamers; oligopeptides or small molecules. There are currently several FDA-approved nanomedicines, but none approved for brain tumor therapy. This review, based both on the study of literature and on the authors own experimental work describes a comprehensive overview of preclinical and clinical research of nanodrugs in therapy of brain tumors. This is an open access article distributed under the terms of the Creative Commons AttributionNonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms. For reprints contact: service@oaepublish.com ReviewOpen Access

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“…The reaction of dextran with 2-methoxypropene leads to the formation of both cyclic and acyclic acetals, causing a switch in solubility and providing a trigger for acid-mediated degradation ). Cyclic and acyclic acetals have completely different rates of hydrolysis (Fife 1965) and the amount of each present can be tailored by the extent of reaction allowing for the modulation of degradation rates from hour to weeks (Meenach 2012). …”

Section: Acetalated Dextran (Ac-dex) As a Novel Drug Delivery Platformmentioning

confidence: 99%

“…The use of Ac-Dex for the tandem delivery of agents significantly advances the development of a targeted biodegradable nanocarrier in that the carrier can be made to degrade fully within a day or up to a week without harmful polymer accumulation or degradation by-products. Thus far, Ac-Dex has been used in particle formulations for applications in immunology/vaccines , (Kanthamneni 2012, and pulmonary therapeutics (Meenach 2012). …”

Section: Acetalated Dextran (Ac-dex) As a Novel Drug Delivery Platformmentioning

confidence: 99%

“…In addition, the conversion of hydroxyl groups on the parent dextran to acetal group was at least 80% for all batches of Ac-Dex, indicating good coverage of acetals on the polymer backbone. The reported CAC value is appropriate for the desired application as Ac-Dex with this property is known to degrade with a few days , Meenach 2012, which is appropriate for the application of nanoparticles to tumors.…”

Section: Characterization Of Acetalated Dextran (Ac-dex)mentioning

confidence: 99%

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Tumor-penetrating acetalated dextran nanoparticles capable of tandem delivery of agents for the treatment of lung cancer

Sun

Meenach

2014

2014 40th Annual Northeast Bioengineering Conference (NEBEC)

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The overall survival rate for patients diagnosed with lung cancer is still extremely low and many affected patients are not eligible for first-line treatments such as surgery, chemotherapy, and radiation for the treatment due to the severe side effects associated with these therapies. Paclitaxel (PTX) along with imatinib mesylate are currently first-line therapies for many types of cancer (Kelly 2001, Schiller 2002.However, the successful delivery of paclitaxel faces many challenges due to its lipophilic nature and high protein affinity, which often results in low bioavailability. While the enhanced permeability and retention (EPR) effect has served as a key rationale for using nanoparticles to treat solid tumors, as it allows for increased uptake of NPs at the tumor site, it often does not enable uniform delivery of these particles to all regions of tumors. Tumor-penetrating peptides show great promise in overcoming the relevant physiological barriers preventing accumulation and penetrating into the avascular region of tumors. iRGD (internalizing RGD, CRGDKDPDC), has been shown to effectively target and penetrate both in vitro multicellular spheroids (MCS) and in vivo animal model tumors when conjugated to drugs or nanoparticles (Sugahara 2010). For the described research, I hypothesize that iRGD-conjugated nanoparticles containing PTX and imatinib will more effectively home to and penetrate lung cancer tumor spheroids for more effective treatment of this dismal disease.In particular, acetalated dextran (Ac-Dex) nanoparticles were synthesized to contain PTX and/or imatinib. These particles were shown to have sizes appropriate for systemic delivery (approximately 250 nm) and exhibited smooth, round morphology.All particle systems exhibited favorable homogeneity as evidenced by low polydispersity index values (less than 0.20) and were nearly neutral in charge with zeta potentials near zero. Both PTX and imatinib were successfully loaded into the nanoparticles with 50 and 14 weight % loading, respectively. 80% of iRGD was conjugated to the nanoparticles and the peptide showed affinity for A549 lung adenocarcinoma cells in vitro. A549 multicellular spheroids were generated to allow for evaluation of the newly developed therapeutics. Finally, in vitro analysis using A549 cells showed that the drug-loaded nanoparticles were more effective at killing cells than pure drugs. Overall, this work shows the promise of Ac-Dex drug-loaded nanoparticles conjugated with iRGD to enhance the treatment of lung cancer.iv ACKNOWLEDGMENTS

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Enhanced stability of horseradish peroxidase encapsulated in acetalated dextran microparticles stored outside cold chain conditions

Cited by 57 publications

References 26 publications

Host-mediated Leishmania donovani treatment using AR-12 encapsulated in acetalated dextran microparticles

Host-mediated Leishmania donovani treatment using AR-12 encapsulated in acetalated dextran microparticles

Nanocarrier drugs in the treatment of brain tumors

Tumor-penetrating acetalated dextran nanoparticles capable of tandem delivery of agents for the treatment of lung cancer

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