An injectable drug delivery platform for sustained combination therapy

Baumann, M. Douglas; Kang, Catherine E.; Stanwick, Jason C.; Wang, Yuanfei; Kim, Howard; Lapitsky, Yakov; Shoichet, Molly S.

doi:10.1016/j.jconrel.2009.05.009

Cited by 174 publications

(119 citation statements)

References 44 publications

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“…Therefore, developing dual drug delivery systems (DDDS), which can control the release behaviour of each drug, is needed. However, so far there has been limited research on dual drug delivery systems [2][3][4][5][6][7][8][9] .…”

Section: Introductionmentioning

confidence: 99%

Dual Drug Release of Triamterene and Aminophylline from Poly (N-Isopropylacrylamide) Hydrogels

Castro

Mosquera

Katime³

2012

Nanomaterials and Nanotechnology

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We used temperature-sensitive poly(Nisopropylacrylamide) hydrogels as drug delivery systems, so changes in body temperature induced by pathogens could act like external stimuli to activate controlled release of the drugs incorporated in the hydrogel. In the distilled water combined release studies, we chose two model drugs: aminophylline and triamterene. The amount of drug released was measured by UV-Vis spectroscopy following the evolution of the absorption peaks of aminophylline (271 nm) and triamterene (365 nm). The maximum release time was greater for triamterene than for aminophylline at 37 ºC, so these time-release profiles enabled the active ingredients to work over different periods of time. By increasing molar mass or solubility of the drug, we observed that the diffusion coefficient decreased. On the contrary, increasing hydrophobicity of the drug leads to a diffusion coefficient increase. The evolution of pore size distribution of hydrogels during loading and releasing was measured by quasi-elastic light scattering and by environmental electronic scanning microscope. When loading and releasing the drugs, the pore size of the hydrogel decreased and increased again without reaching the initial pore size of the hydrogel, respectively. We observed that the greater the concentration of drug loaded into the hydrogel, the greater the reduction in pore size.

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Section: Introductionmentioning

confidence: 99%

Dual Drug Release of Triamterene and Aminophylline from Poly (N-Isopropylacrylamide) Hydrogels

Castro

Mosquera

Katime³

2012

Nanomaterials and Nanotechnology

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“…In this case, the NCC/drug suspensions were transferred to dialysis bags with a molecular weight cutoff of 10,000 Da (Spectra/Por ® , Spectrum Laboratories, Inc., Rancho Dominguez, CA, USA) and dialyzed against dH 2 O overnight in the dark at 4°C. The concentration of unbound drug in the dialysate was determined by UV Vis spectroscopy, allowing for the calculation of the amount of drug bound to the NCC according to Equation 1.…”

Section: Ncc Drug Bindingmentioning

confidence: 99%

“…1 Despite an extended history of use in tableting, there is still considerable c ontinuing research into the use of MCC and other types of cellulose in advanced pelleting s ystems whereby the rate of tablet disintegration and drug release may be controlled by microparticle inclusion, excipient layering or tablet coating. [2][3][4][5][6][7][8][9][10][11] Derivatized cellulose has also been used extensively in pharmaceutical preparations so that ethyl cellulose, methyl cellulose, carboxymethyl cellulose, and numerous other forms are used in oral, topical, and injectable formulations. For example, c arboxymethyl cellulose is the primary component of Seprafilm™, which is applied to surgical sites to prevent post surgical adhesions.…”

Section: Introductionmentioning

confidence: 99%

“…Recently, the use of MCC in self-emulsifying drugdelivery systems and semisolid injectable formulations has also been described. 2,12 The use of these forms of cellulose in such formulations points to the inertness and excellent biocompatibility of cellulose in humans. Additionally, hydroxypropyl methyl cellulose has recently been used as a hydrogel matrix for chondrocyte implantation into animal joints for cartilage repair.…”

Section: Introductionmentioning

confidence: 99%

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The use of nanocrystalline cellulose for the binding and controlled release of drugs

Jackson¹,

Letchford²,

Wasserman³

et al. 2011

IJN

109

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The objective of this work was to investigate the use of nanocrystalline cellulose (NCC) as a drug delivery excipient. NCC crystallites, prepared by an acid hydrolysis method, were shown to have nanoscopic dimensions and exhibit a high degree of crystallinity. These crystallites bound significant quantities of the water soluble, ionizable drugs tetratcycline and doxorubicin, which were released rapidly over a 1-day period. Cetyl trimethylammonium bromide (CTAB) was bound to the surface of NCC and increased the zeta potential in a concentration-dependent manner from −55 to 0 mV. NCC crystallites with CTAB-modified surfaces bound significant quantities of the hydrophobic anticancer drugs docetaxel, paclitaxel, and etoposide. These drugs were released in a controlled manner over a 2-day period. The NCC-CTAB complexes were found to bind to KU-7 cells, and evidence of cellular uptake was observed.

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“…These FGF2-loaded nanoparticles were dispersed in a formulation of HAMC optimized for long-term drug delivery based on in vitro swelling, degradation and drug release [Baumann et al, 2009]. The safety and biocompatibility of this composite HAMC/PLGA was established when injected in the intrathecal space [Baumann et al, 2010].…”

Section: Introductionmentioning

confidence: 99%

Localized and Sustained Delivery of Fibroblast Growth Factor-2 from a Nanoparticle-Hydrogel Composite for Treatment of Spinal Cord Injury

Kang

Baumann

Tator

et al. 2012

Cells Tissues Organs

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After traumatic spinal cord injury, grossly injured blood vessels leak blood and fluid into the parenchyma, leading to a large cystic cavity. Fibroblast growth factor-2 (FGF2) can reduce immediate vasoconstriction of vessels in the tissue surrounding the primary injury and promote angiogenesis. A localized delivery system would both achieve restricted delivery of FGF2 to the spinal cord and limit possible systemic effects such as mitogenesis. To enhance the endogenous angiogenic response after spinal cord injury, FGF2 was encapsulated in poly(lactide-co-glycolide) (PLGA) nanoparticles which were embedded in a biopolymer blend of hyaluronan and methylcellulose (HAMC) and then injected into the intrathecal space. Treatment began immediately after a 26 g clip compression spinal cord injury in rats and consisted of intrathecal delivery of FGF2 from the HAMC/PLGA/FGF2 composite. Control animals received intrathecal HAMC loaded with blank nanoparticles, intrathecal HAMC alone or intrathecal artificial cerebrospinal fluid alone. Sustained and localized delivery of FGF2 from composite HAMC/PLGA/FGF2 achieved higher blood vessel density in the dorsal horns 28 days post-injury, due to either greater angiogenesis near the epicenter of the injury or vasoprotection acutely after spinal cord injury. Importantly, delivery of FGF2 from composite HAMC/PLGA/FGF2 did not produce proliferative lesions that had been previously reported for FGF2 delivered locally using a minipump/catheter. These results suggest that localized and sustained delivery with composite HAMC/PLGA/FGF2 is an excellent system to deliver biomolecules directly to the spinal cord, thereby circumventing the blood spinal cord barrier and avoiding systemic side effects.

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An injectable drug delivery platform for sustained combination therapy

Cited by 174 publications

References 44 publications

Dual Drug Release of Triamterene and Aminophylline from Poly (N-Isopropylacrylamide) Hydrogels

Dual Drug Release of Triamterene and Aminophylline from Poly (N-Isopropylacrylamide) Hydrogels

The use of nanocrystalline cellulose for the binding and controlled release of drugs

Localized and Sustained Delivery of Fibroblast Growth Factor-2 from a Nanoparticle-Hydrogel Composite for Treatment of Spinal Cord Injury

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