Particle size reduction to the nanometer range: a promising approach to improve buccal absorption of poorly water-soluble drugs

Rao, Shasha; Song, Yunmei; Peddie, Frank; Evans, Allan M.

doi:10.2147/ijn.s19151

Cited by 31 publications

(9 citation statements)

References 28 publications

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“…Additionally, we investigated the effect of nanoparticle diameter on in vivo efficacy, as size is often regarded as an important factor in delivery ability to various physiological targets. 23,24 All LNPs formulated in this study had diameters less than 300 nm. For these diameters, no correlation between size and in vivo efficacy was observed at an siRNA dose of 5 mg/kg (Figure 5b) or at lower siRNA doses (< 0.5 mg/kg, data not shown).…”

Section: Resultsmentioning

confidence: 90%

In Vitro–In Vivo Translation of Lipid Nanoparticles for Hepatocellular siRNA Delivery

Whitehead

Matthews²,

Chang³

et al. 2012

ACS Nano

103

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A significant challenge in the development of clinically-viable siRNA delivery systems is a lack of in vitro – in vivo translatability: many delivery vehicles that are initially promising in cell culture do not retain efficacy in animals. Despite its importance, little information exists on the predictive nature of in vitro methodologies, most likely due to the cost and time associated with generating in vitro – in vivo data sets. Recently, high-throughput techniques have been developed that have allowed the examination of hundreds of lipid nanoparticle formulations for transfection efficiency in multiple experimental systems. The large resulting data set has allowed the development of correlations between in vitro and characterization data and in vivo efficacy for hepatocellular delivery vehicles. Consistency of formulation technique and the type of cell used for in vitro experiments was found to significantly affect correlations, with primary hepatocytes and HeLa cells yielding the most predictive data. Interestingly, in vitro data acquired using HeLa cells was more predictive of in vivo performance than mouse hepatoma Hepa1-6 cells. Of the characterization parameters, only siRNA entrapment efficiency was partially predictive of in vivo silencing potential, while zeta potential and, surprisingly, nanoparticle size (when < 300 nm) as measured by dynamic light scattering were not. These data provide guiding principles in the development of clinically-viable siRNA delivery materials and have the potential to reduce experimental costs while improving the translation of materials into animals.

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Section: Resultsmentioning

confidence: 90%

In Vitro–In Vivo Translation of Lipid Nanoparticles for Hepatocellular siRNA Delivery

Whitehead

Matthews²,

Chang³

et al. 2012

ACS Nano

103

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“…Several clinical studies have reported the use of ultramicronized PEA (um-PEA) in the treatment of various syndromes associated with chronic pain that are poorly responsive to standard therapies [ 24 – 26 ]. The ultramicronization process is often used in the preparation of pharmaceuticals, as it yields a crystalline structure with higher energy content and smaller particle size which contributes to better distribution and diffusion and therefore a greater pharmacological efficacy [ 27 , 28 ]. Interestingly, a recent study reported that micronized PEA/um-PEA displayed better oral efficacy compared to nonmicronized PEA in a rat model of inflammatory pain [ 29 ].…”

Section: Introductionmentioning

confidence: 99%

Palmitoylethanolamide in the Treatment of Failed Back Surgery Syndrome

Paladini

Varrassi

Bentivegna

et al. 2017

Pain Research and Treatment

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Introduction This observational study was designed to evaluate the efficacy of ultramicronized palmitoylethanolamide (um-PEA) (Normast®) administration, as add-on therapy for chronic pain, in the management of pain-resistant patients affected by failed back surgery syndrome. Methods A total of 35 patients were treated with tapentadol (TPD) and pregabalin (PGB). One month after the start of standard treatment, um-PEA was added for the next two months. Pain was evaluated by the Visual Analogue Scale (VAS) at the time of enrollment (T0) and after one (T1), two (T2), and three (T3) months. Results After the first month with TDP + PGB treatment only, VAS score decreased significantly from 5.7 ± 0.12 at the time of enrollment (T0) to 4.3 ± 0.11 (T1) (p < 0.0001); however, it failed to provide significant subjective improvement in pain symptoms. Addition of um-PEA led to a further and significant decrease in pain intensity, reaching VAS scores of 2.7 ± 0.09 (T2) and 1.7 ± 0.11 (T3, end of treatment) (p < 0.0001) without showing any side effects. Conclusions This observational study provides evidence, albeit preliminary, for the efficacy and safety of um-PEA (Normast) as part of a multimodal therapeutic regimen in the treatment of pain-resistant patients suffering from failed back surgery syndrome.

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“…The milk distribution study showed that nano-sized lasalocid exhibited faster distribution of the active compound in the milk than microsized lasalocid. This may be the result of nanosized active compound having faster dissolution characteristics, 41 leading to a faster distribution of the active compound throughout the mammary gland. This is consistent with the finding that best tissue distribution rates are expected when the active compound is administered in a formulation with homogeneously distributed particles of small size.…”

Section: Discussionmentioning

confidence: 99%

Development of intramammary delivery systems containing lasalocid for the treatment of bovine mastitis: impact of solubility improvement on safety, efficacy, and milk distribution in dairy cattle

Wang¹,

Song²,

Petrovski³

et al. 2015

DDDT

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BackgroundMastitis is a major disease of dairy cattle. Given the recent emergence of methicillin-resistant Staphylococcus aureus as a cause of bovine mastitis, new intramammary (IMA) treatments are urgently required. Lasalocid, a member of the polyether ionophore class of antimicrobial agents, has not been previously administered to cows by the IMA route and has favorable characteristics for development as a mastitis treatment. This study aimed to develop an IMA drug delivery system (IMDS) of lasalocid for the treatment of bovine mastitis.MethodsMinimum inhibitory concentrations (MICs) were determined applying the procedures recommended by the Clinical and Laboratory Standards Institute. Solid dispersions (SDs) of lasalocid were prepared and characterized using differential scanning calorimetry and Fourier transform infrared spectroscopy. IMDSs containing lasalocid of micronized, nano-sized, or as SD form were tested for their IMA safety in cows. Therapeutic efficacy of lasalocid IMDSs was tested in a bovine model involving experimental IMA challenge with the mastitis pathogen Streptococcus uberis.ResultsLasalocid demonstrated antimicrobial activity against the major Gram-positive mastitis pathogens including S. aureus (MIC range 0.5–8 μg/mL). The solubility test confirmed limited, ion-strength-dependent water solubility of lasalocid. A kinetic solubility study showed that SDs effectively enhanced water solubility of lasalocid (21–35-fold). Polyvinylpyrrolidone (PVP)-lasalocid SD caused minimum mammary irritation in treated cows and exhibited faster distribution in milk than either nano or microsized lasalocid. IMDSs with PVP-lasalocid SD provided effective treatment with a higher mastitis clinical and microbiological cure rate (66.7%) compared to cloxacillin (62.5%).ConclusionLasalocid SD IMDS provided high cure rates and effectiveness in treating bovine mastitis with acceptable safety in treated cows.

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Particle size reduction to the nanometer range: a promising approach to improve buccal absorption of poorly water-soluble drugs

Cited by 31 publications

References 28 publications

In Vitro–In Vivo Translation of Lipid Nanoparticles for Hepatocellular siRNA Delivery

In Vitro–In Vivo Translation of Lipid Nanoparticles for Hepatocellular siRNA Delivery

Palmitoylethanolamide in the Treatment of Failed Back Surgery Syndrome

Development of intramammary delivery systems containing lasalocid for the treatment of bovine mastitis: impact of solubility improvement on safety, efficacy, and milk distribution in dairy cattle

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