Preclinical study of Doxorubicine-loaded liposomal drug delivery for the treatment of head and neck cancer: Optimization by Box-Behnken statistical design

Acta Biochimica Polonica ◽

10.18388/abp.2020_5142 ◽

2020 ◽

Author(s):

Baihui Yang

Keyword(s):

Drug Delivery ◽

Particle Size ◽

Head And Neck Cancer ◽

Head And Neck ◽

Neck Cancer ◽

Average Particle Size ◽

Statistical Design ◽

Liposomal Formulation ◽

Average Particle

The present investigation aimed at developing Doxorubicin (DOX)-loaded liposome-mediated drug delivery system for head and neck cancer. The liposomes were prepared by film hydration technique using egg phosphatidylcholine and cholesterol using Box-Behnken statistical design. The prepared liposomes were evaluated for the percentage encapsulation efficiency, particle size and in vitro release. The average particle size of the DOX-encapsulating liposomes formulated by thin-film hydration technique was between 150.5 nm and 200 nm with an average particle size of 165.80 nm. The PDI (Polydispersity index) was found to be 0.315 which indicated that particles were monodispersed and narrow-dispersed. In vitro drug release of DOX-loaded liposomes and DOX-loaded peptide-conjugated liposomes was performed in phosphate buffered saline (pH 7.4) and both formulations showed sustained release behavior over the period of 40 hours. The optimized liposomal formulation was conjugated to a peptide and subsequently radiolabeled with 186Re-perrhenate solution and BMEDA-glucoheptonate-stannous chloride solution. Comparative cytotoxicity assay of DOX, DOX-liposomes and DOX-liposomes-peptide on SCC9 cells was performed and it was found that liposomal formulation was not cytotoxic. The antitumor efficacy of 186Re-liposomes, unlabelled liposomes, 186Re-perrhenate solution and 186Re-BMEDA solution was determined in SCC cell lines injected into BALB/c-nu/nu athymic nude rats. The efficacy of antitumor activity was found to be in the following order: peptide-conjugated DOX-loaded liposomes>unlabelled liposomes>186Re-perrhenate solution>186Re-BMEDA solution. The present investigation showed that peptide-conjugated DOX-loaded liposomes significantly suppress the tumor growth in the nude rat model. These results suggest the significant potential of liposomes as carriers for clinical applications in head and neck cancer.

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Indinavir-Loaded Nanostructured Lipid Carriers to Brain Drug Delivery: Optimization, Characterization and Neuropharmacokinetic Evaluation

Current Drug Delivery ◽

10.2174/1567201816666190123124429 ◽

2019 ◽

Vol 16 (4) ◽

pp. 341-354 ◽

Cited By ~ 1

Author(s):

Mohammad Nasiri ◽

Amir Azadi ◽

Mohammad Reza Saghatchi Zanjani ◽

Mehrdad Hamidi

Keyword(s):

Drug Delivery ◽

Particle Size ◽

Zeta Potential ◽

Average Particle Size ◽

In Vitro Release ◽

Free Drug ◽

Average Particle ◽

The Brain

Purpose: As an anti-retroviral Protease Inhibitor (PI), Indinavir (IDV) is part of the regimen known as Highly Active Anti-Retroviral Therapy (HAART) widely used for Human Immunodeficiency Virus (HIV) infection. The drug efficiency in treatment of the brain manifestations of HIV is, however, limited which is mainly due to the efflux by P-glycoprotein (P-gp) expressed at the Blood-Brain Barrier (BBB). Methods: To overcome the BBB obstacle, NLCs were used in this study as carriers for IDV, which were optimized through two steps: a “one-factor-at-a-time” screening followed by a systematic multiobjective optimization. Spherical smooth-surfaced Nanoparticles (NPs), average particle size of 161.02±4.8 nm, Poly-Dispersity Index (PDI) of 0.293±0.07, zeta potential of -40.62±2.21 mV, entrapment efficiency of 93±1.58%, and loading capacity of 9.15±0.15% were obtained after optimization which were, collectively, appropriate in terms of the objective of this study. Result: The surface of the optimized NPs was, then, modified with human Transferrin (TR) to improve the drug delivery. The particle size, zeta potential, and PDI of the TR-modified NLCs were 185.29±6.7nm, -28.68±3.37 mV, and 0.247±0.06, respectively. The in vitro release of IDV molecules from the NPs was best fitted to the Weibull model indicating hybrid diffusion/erosion behavior. Conclusion: As the major in vivo findings, compared to the free drug, the NLCs and TR-NLCs displayed significantly higher and augmented concentrations in the brain. In this case, NLC and TR-NLC were 6.5- and 32.75-fold in their values of the brain uptake clearance compared to free drug.

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Formulating SLN and NLC as Innovative Drug Delivery Systems for Non-Invasive Routes of Drug Administration

Current Medicinal Chemistry ◽

10.2174/0929867326666190624155938 ◽

2020 ◽

Vol 27 (22) ◽

pp. 3623-3656 ◽

Cited By ~ 1

Author(s):

Bruno Fonseca-Santos ◽

Patrícia Bento Silva ◽

Roberta Balansin Rigon ◽

Mariana Rillo Sato ◽

Marlus Chorilli

Keyword(s):

Drug Delivery ◽

Particle Size ◽

Drug Release ◽

Drug Loading ◽

Average Particle Size ◽

Delivery Systems ◽

Average Particle ◽

Minor Importance ◽

Routes Of Administration ◽

Non Invasive

Colloidal carriers diverge depending on their composition, ability to incorporate drugs and applicability, but the common feature is the small average particle size. Among the carriers with the potential nanostructured drug delivery application there are SLN and NLC. These nanostructured systems consist of complex lipids and highly purified mixtures of glycerides having varying particle size. Also, these systems have shown physical stability, protection capacity of unstable drugs, release control ability, excellent tolerability, possibility of vectorization, and no reported production problems related to large-scale. Several production procedures can be applied to achieve high association efficiency between the bioactive and the carrier, depending on the physicochemical properties of both, as well as on the production procedure applied. The whole set of unique advantages such as enhanced drug loading capacity, prevention of drug expulsion, leads to more flexibility for modulation of drug release and makes Lipid-based nanocarriers (LNCs) versatile delivery system for various routes of administration. The route of administration has a significant impact on the therapeutic outcome of a drug. Thus, the non-invasive routes, which were of minor importance as parts of drug delivery in the past, have assumed added importance drugs, proteins, peptides and biopharmaceuticals drug delivery and these include nasal, buccal, vaginal and transdermal routes. The objective of this paper is to present the state of the art concerning the application of the lipid nanocarriers designated for non-invasive routes of administration. In this manner, this review presents an innovative technological platform to develop nanostructured delivery systems with great versatility of application in non-invasive routes of administration and targeting drug release.

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Hydroxyurea, fluorouracil, and concomitant radiotherapy in poor-prognosis head and neck cancer: a phase I-II study.

Journal of Clinical Oncology ◽

10.1200/jco.1989.7.6.761 ◽

1989 ◽

Vol 7 (6) ◽

pp. 761-768 ◽

Cited By ~ 97

Author(s):

E E Vokes ◽

W R Panje ◽

R L Schilsky ◽

R Mick ◽

A M Awan ◽

...

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Neck Cancer ◽

Poor Prognosis ◽

Local Therapy ◽

Complete Response ◽

Synergistic Activity ◽

Dose Levels ◽

Concomitant Radiotherapy

Hydroxyurea and fluorouracil (5-FU) are active cytotoxic drugs in head and neck cancer and have shown synergistic activity in vitro. Both drugs also act as radiosensitizers. Therefore, we administered radiotherapy at daily fractions of 180 to 200 cGy with simultaneous continuous infusion 5-FU at 800 mg/m2/d and escalating daily doses of hydroxyurea for five days. Cycles were repeated every other week until completion of radiotherapy. Thirty-nine inoperable patients were treated at six dose levels of hydroxyurea ranging from 500 mg to 3,000 mg orally daily. Little effect of hydroxyurea on the WBC or platelet count was noted in patients receiving less than 2,000 mg daily, whereas both parameters decreased progressively in patients receiving 2,000 mg daily or more. Mucositis occurred at all dose levels, requiring frequent dose reduction of 5-FU; however, in patients receiving a daily hydroxyurea dose of 2,000 mg or less, the median weekly 5-FU dose administered was 1,725 mg/m2 (86% of the intended 5-FU dose), whereas at daily hydroxyurea doses exceeding 2,000 mg, the median weekly 5-FU dose decreased to 1,133 mg/m2 (57%) (P = .001). Of 15 evaluable patients with recurrent disease after prior local therapy only one failed to respond; six had a complete response (CR), and eight a partial response (PR). Of 17 evaluable patients without prior local therapy, 12 had a CR, with no patient developing recurrence in the irradiated field to date; five patients had a PR. We conclude that the recommended dose of hydroxyurea in this regimen is 2,000 mg daily. That dose will cause mild to moderate myelosuppression and will allow for delivery of greater than 80% of the intended 5-FU dose. The activity of this regimen in poor-prognosis head and neck cancer exceeds 90%; its further investigation in previously untreated patients is warranted.

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Ionizing radiation affects the composition of the proteome of extracellular vesicles released by head-and-neck cancer cells in vitro

Journal of Radiation Research ◽

10.1093/jrr/rrz001 ◽

2019 ◽

Vol 60 (3) ◽

pp. 289-297 ◽

Cited By ~ 17

Author(s):

Agata Abramowicz ◽

Anna Wojakowska ◽

Lukasz Marczak ◽

Malgorzata Lysek-Gladysinska ◽

Mateusz Smolarz ◽

...

Keyword(s):

Head And Neck Cancer ◽

Ionizing Radiation ◽

Head And Neck ◽

Cancer Cells ◽

Extracellular Vesicles ◽

Neck Cancer

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Water-Dispersible Phytosterol Nanoparticles: Preparation, Characterization, and in vitro Digestion

Frontiers in Nutrition ◽

10.3389/fnut.2021.793009 ◽

2022 ◽

Vol 8 ◽

Author(s):

Ao Li ◽

Aixia Zhu ◽

Di Kong ◽

Chunwei Wang ◽

Shiping Liu ◽

...

Keyword(s):

Particle Size ◽

Soybean Lecithin ◽

Average Particle Size ◽

Soy Protein Isolate ◽

In Vitro Digestion ◽

Bimodal Distribution ◽

Average Particle ◽

Food Ingredients ◽

The Impact

For improving solubility and bioaccessibility of phytosterols (PS), phytosterol nanoparticles (PNPs) were prepared by emulsification–evaporation combined high-pressure homogenization method. The organic phase was formed with the dissolved PS and soybean lecithin (SL) in anhydrous ethanol, then mixed with soy protein isolate (SPI) solution, and homogenized into nanoparticles, followed by the evaporation of ethanol. The optimum fabrication conditions were determined as PS (1%, w/v): SL of 1:4, SPI content of 0.75% (w/v), and ethanol volume of 16 ml. PNPs were characterized to have average particle size 93.35 nm, polydispersity index (PDI) 0.179, zeta potential −29.3 mV, and encapsulation efficiency (EE) 97.3%. The impact of temperature, pH, and ionic strength on the stability of fabricated PNPs was determined. After 3-h in vitro digestion, the bioaccessibility of PS in nanoparticles reached 70.8%, significantly higher than the 18.2% of raw PS. Upon freeze-drying, the particle size of PNPs increased to 199.1 nm, resulting in a bimodal distribution. The solubility of PS in water could reach up to 2.122 mg/ml, ~155 times higher than that of raw PS. Therefore, this study contributes to the development of functional PS-food ingredients.

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Sodium Alginate Nanoparticles of Isoniazid: Preparation and Evaluation

International Journal of Pharmaceutical Sciences and Drug Research ◽

10.25004/ijpsdr.2019.110616 ◽

2019 ◽

Vol 11 (06) ◽

Author(s):

Sumit Kumar ◽

Dinesh Chandra Bhatt

Keyword(s):

Particle Size ◽

Sodium Alginate ◽

Encapsulation Efficiency ◽

Drug Loading ◽

Average Particle Size ◽

Average Particle ◽

In Vitro Drug Release ◽

Ionotropic Gelation ◽

Preparation And Evaluation

Fabrication and evaluation of the Isoniazid loaded sodium alginate nanoparticles (NPs) was main objective of current investigation. These NPs were engineered using ionotropic gelation technique. The NPs fabricated, were evaluated for average particle size, encapsulation efficiency, drug loading, and FTIR spectroscopy along with in vitro drug release. The particle size, drug loading and encapsulation efficiency of fabricated nanoparticles were ranging from 230.7 to 532.1 nm, 5.88% to 11.37% and 30.29% to 59.70% respectively. Amongst all batches studied formulation F-8 showed the best sustained release of drug at the end of 24 hours.

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Preparation and characterization of domperidone nanoparticles for dissolution improvement

Iraqi Journal of Pharmaceutical Sciences ( P-ISSN 1683 - 3597 E-ISSN 2521 - 3512) ◽

10.31351/vol27iss1pp39-52 ◽

2018 ◽

Vol 27 (1) ◽

pp. 39-52

Author(s):

Mohammed Sabar Al-lami ◽

Malath H. Oudah ◽

Firas A. Rahi

Keyword(s):

Particle Size ◽

Average Particle Size ◽

In Vitro Release ◽

Methyl Cellulose ◽

Precipitation Method ◽

Average Particle ◽

Antisolvent Precipitation ◽

Stirring Time

This study was carried out to prepare and characterize domperidone nanoparticles to enhance solubility and the release rate. Domperidone is practically insoluble in water and has low and an erratic bioavailability range from 13%-17%. The domperidone nanoparticles were prepared by solvent/antisolvent precipitation method at different polymer:drug ratios of 1:1 and 2:1 using different polymers and grades of poly vinyl pyrolidone, hydroxy propyl methyl cellulose and sodium carboxymethyl cellulose as stabilizers. The effect of polymer type, ratio of polymer:drug, solvent:antisolvent ratio, stirring rate and stirring time on the particle size, were investigated and found to have a significant (p? 0.05) effect on particle size. The best formula was obtained with lowest average particle size of 84.05. This formula was studied for compatibility by FTIR and DSC, surface morphology by FESEM and crystalline state by XRPD. Then domperidone nanoparticles were formulated into a simple capsule dosage form in order to study of the in vitro release of drug from nanoparticles in comparison raw drug and mixture of polymer:drug ratios of 2:1. The release of domperidone from best formula was highly improved with a significant (p? 0.05) increase.

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Dual synthesis of Silver and Iron oxide nanoparticles from edible greens Amaranthus Viridis and their in vitro antioxidant activity and antimicrobial studies

Current Biotechnology ◽

10.2174/2211550110666211206101654 ◽

2021 ◽

Vol 10 ◽

Author(s):

Venkata Subbaiah Kotakadi ◽

Bhulakshmi Kolapalli ◽

Susmila Aparna Gaddam ◽

Sai Gopal Divi Venkata Ramana

Keyword(s):

Antioxidant Activity ◽

Particle Size ◽

Green Synthesis ◽

Metallic Nanoparticles ◽

Iron Nanoparticles ◽

Average Particle Size ◽

Leafy Vegetable ◽

Size Analysis ◽

Average Particle

Background: There is an increasing commercial demand for nanoparticles due to their wide applicability in various areas such as chemistry, catalysis, energy and medicine. Metallic nanoparticles are traditionally synthesized by wet chemical techniques where the chemicals used are quite often toxic and flammable. Objective: In the present study, we described a simple, cost effective and environmentally-friendly technique for green synthesis of silver and iron nanoparticles by using the aqueous extract of leafy vegetable Amaranthus viridis as a reducing agent. Methods: The silver and Iron nanoparticles (Av-AgNPs, Av-IONPs) were characterized by different spectral methods. The surface Plasmon resonance spectrums of Av-AgNPs, Av-IONPs were recorded at 422nm and 261nm. The Scanning electron microscopy (SEM) analysis reveals that the Av-AgNPs, Av-IONPs are roughly spherical in shape. Energy dispersive absorption spectroscopy (EDAX) of biosynthesized Av-AgNPs, Av-IONPs indicates the reduction of silver ions to elemental silver and iron ions to elemental iron. Results: The particle size analysis of Av-AgNPs and Av-IONPs was carried out by Dynamic light scattering (DLS) method the results reveal that both Av-AgNPs and Av-IONPs were polydispered in nature. The average particle size of Av-AgNPs is 55.8 nm with a polydispered index (PI) of 0.297, similarly the average particle size of Av-IONPs is 80.6 nm with an polydispered index (PI) of 0.469. Zeta-potential of Av-AgNPs was detected at -24.6 mV and Av-IONPs were detected at 28.8 mV, the result reveals that they high stability due their high negative charge and positive charge respectively. The dual synthesized Av-AgNPs, Av-IONPs exhibits excellent antioxidant activity by DPPH, H2O2 and NO methods. DPPH was proven to be the best when compared with the other two methods. The biosynthesized Av-AgNPs, Av-IONPs proved to have very good antimicrobial activity against gram +ve and gram –ve bacteria. Conclusion: when compared with standard antibiotic. There were several reports on green synthesis of metal nanoparticles using various plant parts, but here edible leafy vegetable Amaranthus viridis was used for biosynthesis of both Av-AgNPs and Av-IONPs.

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