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. 2022 Nov 2;12(48):31402-31411.
doi: 10.1039/d2ra05639a. eCollection 2022 Oct 27.

In-depth drug delivery to tumoral soft tissues via pH responsive hydrogel

Shumaila Sarwar  1   2 , Sajid Bashir  2 , Mulazim Hussain Asim  2 , Fakhera Ikram  1 , Arsalan Ahmed  1 , Ume Omema  1 , Anila Asif  1 , Aqif Anwar Chaudhry  1 , Yong Hu  3 , Cem Bulent Ustundag  4
Affiliations

In-depth drug delivery to tumoral soft tissues via pH responsive hydrogel

Shumaila Sarwar et al. RSC Adv. .

Abstract

A pH responsive nanoparticle-hydrogel hybrid drug delivery system was investigated for in-depth anticancer drug delivery to solid tumours. It consists of acid susceptible polymer nanoparticles loaded in a chitosan hydrogel. The hybrid formulation was characterized by UV-visible spectroscopy, FTIR, SEM, TEM, particle size analysis, zeta potential measurement and viscosity measurement. Drug encapsulation and nanoparticle loading efficiencies were found to be 48% and 72% respectively which describes the efficient interaction of the chemical entities in this hybrid drug delivery system. The hydrogel exhibited pH responsive behaviour: minimal drug and nanoparticle release at physiological pH but an increase in viscosity under acidic conditions and fast nanoparticle and drug release. The cytotoxicity of the drug loaded hydrogel was investigated against the MCF-7 breast cancer cell line along with the drug and nanoparticles without hydrogel. The drug loaded hydrogel showed a better cytotoxic effect on MCF-7 cancer cells. Thus, drug loaded nanoparticles containing hydrogel could be a better option for maximum drug distribution in tumours.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Fig. 1
Fig. 1. Schematic illustration of formulation and characterization of nanoparticles–hydrogel drug delivery system.
Fig. 2
Fig. 2. Possible molecular interactions between nanoparticles and hydrogel (a) at high pH (structural stability due to hydrogen bonding) and (b) at low pH (disruption in molecular interactions).
Fig. 3
Fig. 3. FTIR spectra of hydrogel and copolymers (a), UV-visible spectra of PCL-PEI-Fol for the estimation of folate (b), and NMR spectra of hydrogel and copolymers.
Fig. 4
Fig. 4. Graphs of size calculation of nanoparticles using dynamic light scattering (a), and charge reversibility of nanoparticles observed at different pH values using zeta potential (b).
Fig. 5
Fig. 5. SEM image of nanoparticles without loading in hydrogel (a), and TEM image nanoparticles after loading in hydrogel (2).
Fig. 6
Fig. 6. Visual images of acidic environment responsive viscosity change (a), and agglomeration of nanoparticles at acidic pH (b).
Fig. 7
Fig. 7. Estimation of gel-to-sol transition of hydrogel in normal and acidic media through capillary rise method (a), release of nanoparticles from hydrogel in acidic and normal media (b), and release of drug from nanoparticles–hydrogel drug delivery system at normal and acidic media (c).
Fig. 8
Fig. 8. Cell viability of nanoparticles–hydrogel drug delivery system and its components against MCF-7 cancer cell line at different time intervals.
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