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. 2022 Jun 30:13:911771.
doi: 10.3389/fphar.2022.911771. eCollection 2022.

Formulation Development and Characterization of pH Responsive Polymeric Nano-Pharmaceuticals for Targeted Delivery of Anti-Cancer Drug (Methotrexate)

Farhad Ullah  1 , Zafar Iqbal  1 , Amjad Khan  2 , Saeed Ahmad Khan  2 , Lateef Ahmad  3 , Amal Alotaibi  4 , Riaz Ullah  5 , Muhammad Shafique  6
Affiliations

Formulation Development and Characterization of pH Responsive Polymeric Nano-Pharmaceuticals for Targeted Delivery of Anti-Cancer Drug (Methotrexate)

Farhad Ullah et al. Front Pharmacol. .

Abstract

Oral administration of pH sensitive/stimuli responsive nanoparticles are gaining importance because of the limited side effects, minimum dose and controlled drug release. The objective of this study was to develop and evaluate pH sensitive polymeric nanoparticles for methotrexate with the aim to maximize the drug release at target site. In the presented study, pH sensitive polymeric nanoparticles of methotrexate were developed through modified solvent evaporation technique using polymer Eudragit S100. Different process parameters like drug to polymer ratio, speed of sonication, concentration of surfactant and time of sonication were optimized by evaluating their effects on particle size, PDI, zeta potential, entrapment/encapsulation efficiency. The developed formulations were evaluated for their size, polydispersity (PDI), zeta potential, encapsulation efficiency, XRD, scanning electron microscopy, in-vitro drug release and stability studies. Best results were obtained with poloxamer-407 and PVA and were selected as surfactants. Physicochemical characterization of the developed formulations showed that the particle size lies in the range 165.7 ± 1.85-330.4 ± 4.19, PDI 0.119 ± 0.02-0.235 ± 0.008, zeta potential -0.163 ± 0.11--5.64 ± 0.36 mV, and encapsulation efficiency more than 61%. The results of scanning electron microscopy revealed that nanoparticles have regular geometry with spherical shape. Initially the drug release occur through diffusion followed by erosion. The present studies showed that MTX-ES100 nanoparticles prepared during this study have the desired physicochemical properties, surface morphology and release characteristics used to target the desired organs.

Keywords: Eudragit; methotrexate; polymeric nanoparticles; solvent evaporation method; targeted drug delivery.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Schematic presentation of the process of preparation of methotrexate loaded polymeric nanoparticles.
FIGURE 2
FIGURE 2
Effect of Eudragit S100 conc. on (A) particles size (B) % Encapsulation efficiency of MTX nanoparticles using different emulsifiers (PVA and Poloxamer-407).
FIGURE 3
FIGURE 3
Effect of concentration of emulsifier (PVA and Poloxamer-407) on particles size, and encapsulation efficiency of MTX nanoparticles using Eudragit S100.
FIGURE 4
FIGURE 4
XRD curve of (A) MTX, (B) Eudragit S100 (C) Poloxamer-407 and (D) MTX- Eudragit S100 nanoparticles (MSX8).
FIGURE 5
FIGURE 5
Graphs showing particle size and zeta potential of optimal formulation of methotrexate loaded nanopatricles.
FIGURE 6
FIGURE 6
SEM images of methotrexate loaded nanoparticles prepared using Eudragit S100.
FIGURE 7
FIGURE 7
In-vitro release profile of methotrexate from eudragit S100 nanoparticles in different simulated GI tract fluids (SGF, simulated gastric fluid; SIF, simulated intestinal fluid; SCF, simulated colonic fluid).
See this image and copyright information in PMC

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