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A Facile and Novel Approach to Manufacture Paclitaxel-Loaded Proliposome Tablet Formulations of Micro or Nano Vesicles for Nebulization.

ABSTRACT: PURPOSE:The aim of this study was to develop novel paclitaxel-loaded proliposome tablet formulations for pulmonary drug delivery. METHOD:Proliposome powder formulations (i.e. F1 - F27) were prepared employing Lactose monohydrate (LMH), Microcrystalline cellulose (MCC) or Starch as a carbohydrate carriers and Soya phosphatidylcholine (SPC), Hydrogenated soya phosphatidylcholine (HSPC) or Dimyristoly phosphatidylcholine (DMPC) as a phospholipid. Proliposome powder formulations were prepared in 1:5, 1:15 or 1:25 w/w lipid phase to carrier ratio (lipid phase; comprising of phospholipid and cholesterol in 1:1 M ratio) and Paclitaxel (PTX) was used as model anticancer drug. RESULTS:Based on flowability studies, out of 27 formulations; F3, F6, and F9 formulations were selected as they exhibited an excellent angle of repose (AOR) (17.24?±?0.43, 16.41?±?0.52 and 15.16?±?0.72°), comparatively lower size of vesicles (i.e. 5.35?±?0.76, 6.27?±?0.59 and 5.43?±?0.68 ?m) and good compressibility index (14.81?±?0.36, 15.01?±?0.35 and 14.56?±?0.14) via Carr's index. The selected formulations were reduced into Nano (N) vesicles via probe sonication, followed by spray drying (SD) to get a dry powder of these formulations as F3SDN, F6SDN and F9SDN, and gave high yield (>53%) and exhibited poor to very poor compressibility index values via Carr's Index. Post tablet manufacturing, F3 tablets formulation showed uniform weight uniformity (129.40?±?3.85 mg), good crushing strength (14.08?±?1.95 N), precise tablet thickness (2.33?±?0.51 mm) and a short disintegration time of 14.35?±?0.56 min, passing all quality control tests in accordance with British Pharmacopeia (BP). Upon nebulization of F3 tablets formulation, Ultrasonic nebulizer showed better nebulization time (8.75?±?0.86 min) and high output rate (421.06?±?7.19 mg/min) when compared to Vibrating mesh nebulizer. PTX-loaded F3 tablet formulations were identified as toxic (60% cell viability) to cancer MRC-5 SV2 cell lines while safe to normal MRC-5 cell lines. CONCLUSION:Overall, in this study LMH was identified as a superior carbohydrate carrier for proliposome tablet manufacturing in a 1:25 w/w lipid to carrier ratio for in-vitro nebulization via Ultrasonic nebulizer.

SUBMITTER: Khan I

PROVIDER: S-EPMC7266847 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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A Facile and Novel Approach to Manufacture Paclitaxel-Loaded Proliposome Tablet Formulations of Micro or Nano Vesicles for Nebulization.

Khan Iftikhar I Lau Katie K Bnyan Ruba R Houacine Chahinez C Roberts Matthew M Isreb Abdullah A Elhissi Abdelbary A Yousaf Sakib S

Pharmaceutical research 20200602 6

<h4>Purpose</h4>The aim of this study was to develop novel paclitaxel-loaded proliposome tablet formulations for pulmonary drug delivery.<h4>Method</h4>Proliposome powder formulations (i.e. F1 - F27) were prepared employing Lactose monohydrate (LMH), Microcrystalline cellulose (MCC) or Starch as a carbohydrate carriers and Soya phosphatidylcholine (SPC), Hydrogenated soya phosphatidylcholine (HSPC) or Dimyristoly phosphatidylcholine (DMPC) as a phospholipid. Proliposome powder formulations were ...[more]

PMID: 32488363

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Project description:In this work, a 3D printed biocompatible micro-optofluidic (MoF) device for two-phase flow monitoring is presented. Both an air-water bi-phase flow and a two-phase mixture composed of micrometric cells suspended on a liquid solution were successfully controlled and monitored through its use. To manufacture the MoF device, a highly innovative microprecision 3D printing technique was used named Projection Microstereolithography (PμSL) in combination with the use of a novel 3D printable photocurable resin suitable for biological and biomedical applications. The concentration monitoring of biological fluids relies on the absorption phenomenon. More precisely, the nature of the transmission of the light strictly depends on the cell concentration: the higher the cell concentration, the lower the optical acquired signal. To achieve this, the microfluidic T-junction device was designed with two micrometric slots for the optical fibers' insertion, needed to acquire the light signal. In fact, both the micro-optical and the microfluidic components were integrated within the developed device. To assess the suitability of the selected biocompatible transparent resin for optical detection relying on the selected working principle (absorption phenomenon), a comparison between a two-phase flow process detected inside a previously fully characterized micro-optofluidic device made of a nonbiocompatible high-performance resin (HTL resin) and the same made of the biocompatible one (BIO resin) was carried out. In this way, it was possible to highlight the main differences between the two different resin grades, which were further justified with proper chemical analysis of the used resins and their hydrophilic/hydrophobic nature via static water contact angle measurements. A wide experimental campaign was performed for the biocompatible device manufactured through the PμSL technique in different operative conditions, i.e., different concentrations of eukaryotic yeast cells of Saccharomyces cerevisiae (with a diameter of 5 μm) suspended on a PBS (phosphate-buffered saline) solution. The performed analyses revealed that the selected photocurable transparent biocompatible resin for the manufactured device can be used for cell concentration monitoring by using ad hoc 3D printed micro-optofluidic devices. In fact, by means of an optical detection system and using the optimized operating conditions, i.e., the optimal values of the flow rate FR=0.1 mL/min and laser input power P∈{1,3} mW, we were able to discriminate between biological fluids with different concentrations of suspended cells with a robust working ability R2=0.9874 and Radj2=0.9811.

Dataset Information

A Facile and Novel Approach to Manufacture Paclitaxel-Loaded Proliposome Tablet Formulations of Micro or Nano Vesicles for Nebulization.

Publications

A Facile and Novel Approach to Manufacture Paclitaxel-Loaded Proliposome Tablet Formulations of Micro or Nano Vesicles for Nebulization.

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