In-Vitro and In-Vivo Evaluation of Velpatasvir- Loaded Mesoporous Silica Scaffolds. A Prospective Carrier for Drug Bioavailability Enhancement

Abstract

The limited aqueous solubility of many active pharmaceutical ingredients (APIs) is responsible for their poor performance and low drug levels in blood and at target sites. Various approaches have been adopted to tackle this issue. Most recently, mesoporous silica nanoparticles (MSN) have gained attention of pharmaceutical scientists for bio-imaging, bio-sensing, gene delivery, drug solubility enhancement, and controlled and targeted drug release. Here, we have successfully incorporated the poorly water soluble antiviral drug velpatasvir (VLP) in MSN. These spherical particles were 186 nm in diameter with polydispersity index of 0.244. Blank MSN have specific surface area and pore diameter of 602.5 ± 0.7 m2/g and 5.9 nm, respectively, which reduced after successful incorporation of drug. Drug was in amorphous form in synthesized VLP-loaded silica particles (VLP-MSN) with no significant interaction with carrier. Pure VLP showed poor dissolution with progressive increment in pH of dissolution media which could limit its availability in systemic circulation after oral administration. After VLP loading in silica carriers, drug released rapidly over a wide range of pH values, i.e., 1.2 to 6.8, thus indicating an improvement in the solubility profile of VLP. These particles were biocompatible, with an LD50 of 448 µg/mL, and in-vivo pharmacokinetic results demonstrated that VLP-MSN significantly enhanced the bioavailability as compared to pure drug. The above results clearly demonstrate satisfactory in-vitro performance, biocompatibility, non-toxicity and in-vivo bioavailability enhancement with VLP-MSN.

Mesoporous Silica Nanoparticles in Chemical Detection: From Small Species to Large Bio-Molecules

“…Since the 1990s, when mesoporous silica particles were published for the first time [ 5 ], many and very interesting applications were developed in different fields such as catalysis [ 6 ], energy applications [ 7 , 8 ] or nano-biomedicine, among others. In the latter, they demonstrated satisfactory in-vitro performance, biocompatibility, non-toxicity and in-vivo bioavailability enhancement [ 9 ], and they were applied both in controlled drug release [ 10 , 11 , 12 ] and in diagnostics [ 13 , 14 ]. Another relevant field is its application in sensing.…”

Short-Term Oral Administration of Mesoporous Silica Nanoparticles Potentially Induced Colon Inflammation in Rats Through Alteration of Gut Microbiota

“…Also, it would be easy for the modification of the functional group on MSNs’ surface to achieve the long period release of therapeutic agents. 2 , 3 For example, Shah’s group 4 fabricated a Velpatasvir (VLP) loaded MSNs with good biocompatibility, and this MSNs based drug delivery system showed prolonged VLP release both in vitro and in vivo. Meantime, a study by Yang et al 5 revealed a preparation of Breviscapine (BRE) loaded MSNs, which showed higher dissolution rate and higher oral absorption than BRE powder.…”

Response Surface Optimization for Simultanous Estimation of Sofosbuvir and Velpatasvir in Human Plasma Sample

“…11,16,17 Most of the chromatographic methods developed by peers used buffer of pH 1.8-3.5 18,13 which affects the shelf life of the column, and some RP-HPLC methods used pH 6-7 in the composition of mobile phase. 6,10,[19][20][21] The mobile phase was composed of organic modifier acetonitrile 30-80% by some peers, 6,13,17,21,22,24 whereas methanol 75% was used in one article 25 and methanol and acetonitrile 40:40 was used in one method development study. 19,26 The wavelength was varied from 240-285 nm and column temperature, flow rate was maintained at 30 0 C, 1 mL/min in all the methods.…”

“…6,10,[19][20][21] The mobile phase was composed of organic modifier acetonitrile 30-80% by some peers, 6,13,17,21,22,24 whereas methanol 75% was used in one article 25 and methanol and acetonitrile 40:40 was used in one method development study. 19,26 The wavelength was varied from 240-285 nm and column temperature, flow rate was maintained at 30 0 C, 1 mL/min in all the methods. The methods were reported using C8 and C18 columns with length varying from 250mm to 150mm.From consideration of all literature method variations of one factor at a time multi factor response optimized method development was initiated.…”