N,N'‐methylenebis(acrylamide)‐crosslinked poly(acrylic acid) particles as doxorubicin carriers: A comparison between release behavior of physically loaded drug and conjugated drug via acid‐labile hydrazone linkage

Abstract

N,N'-methylenebis(acrylamide) (MBA)-crosslinked poly(acrylic acid) (PAA) particles with low degree of cross-linking were synthesized using distillation precipitation polymerization. Size and size distribution of particles were obtained using dynamic light scattering and field emission scanning electron microscopy( and results showed that microspheres had a narrow size dispersity. Proton nuclear magnetic resonance results indicated that amount of cross-linker in structure of particles is a little more than the molar percentage of feeded MBA because of greater activity ratio of MBA than AA. pH-responsive behavior of samples was investigated using UV-vis. absorption at 480 nm where each sample showed a sudden deplete in UV absorbance at a peculiar pH. Synthesized particles were used as carriers of anti-cancer drug doxorubicin using two different approaches including physically loading of drug and drug conjugation via an acid-labile hydrazone linkage. Release results showed that in the first case, amount of released drug has an inverse relationship with the amount of cross-linker in the structure and also, by adding an acid-labile linkage, the amount of burst release decreased drastically. Also, the amount of released drug for conjugated systems was much lesser than particles with physically loaded drug. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 342-348, 2018.

Nano/Microparticles Encapsulation Via Covalent Drug Conjugation

“…Drug release is via ring-opening hydrolysis and thiol exchange [82,83] behavior of doxorubicin that was conjugated onto the structure of nanoparticles. The conjugation was achieved via an acid-labile hydrazone linkage, and the effect of conjugation was compared with the nonconjugated drug [94] (Figure 7). The results of the in vitro investigation revealed that the release of doxorubicin was dependent on the amount of crosslinker.…”

A comparative study on solubility improvement of tetracycline and dexamethasone by poly(propylene imine) and polyamidoamine dendrimers: An insight into cytotoxicity and cell proliferation

“…All the above steps were repeated to synthesize fourth generation PAMAM dendrimer (G4.0 which had 32 primary amines per a dendrimer molecule). It is worth to mention that in synthesis of both dendrimers, the amount of reagents varied while their ratio was kept constant as first step. G0.0: (S( a CH 2  a CH 2 )[N( b CH 2  c CH 2 CO d NH 2  e CH 2  f CH 2  g NH 2 ) 2 ) 2 ] 2 ) 2 1 H NMR (CDCl 3 , 400 MHz, δ H (ppm)): 2.53 (4H,s,a); 2.94 (8H,t,b); 2.57 (8H,t,c); 7.90 (4H, bt,d); 3.31 (8H,bq,e); 2.25 (8H,p,f); 1.58 (8H,t,g). 13 C NMR (CDCl 3 , 400 MHz, δ (ppm)): a: 53.3; b: 49.3; c: 51.6; d: 71.3; e: 36.5; f: 32.7. FT‐IR main peaks (υ/cm −1 ): 1640 (CO); two band regions at 3,250 and 3,330 cm −1 due to asymmetrical and symmetrical NH stretch (Modarresi‐Saryazdi, Haddadi‐Asl, & Salami‐Kalajahi, ; Noein, Haddadi‐Asl, & Salami‐Kalajahi, ). G4.0: (S( a CH 2  a CH 2 )[N( b CH 2  c CH 2 CO d NH 2  e CH 2  f CH 2 N( g CH 2  h CH 2 CO i NH j CH 2  k CH 2 N( l CH 2  m CH 2 CO n NH o CH 2  p CH 2 N( q CH 2  r CH 2 CO s NH t CH 2  u CH 2 N( v CH 2  w CH 2  x CONH y CH 2  z CH 2  α NH 2 ) 2 ) 2 ) 2 ) 2 ) 2 ] 2 1 H NMR (CDCl 3 , 400 MHz, δ H (ppm)): 2.70–2.96 (500H, bm, a,b,c,g,h,l,m,q,r,v,w); 8.05–8.15 (124H, bm, d,i,n,s,x); 3.06–3.37 (248H, bm, e,j,o,t,y); 2.48–2.65 (120H, bm, f,k,p,u); 2.18–2.29 (128H, bp, z); 2.41–2.47 (128H, bt, α). FT‐IR main peaks (υ/cm −1 ): 1,650 (CO), 3,265 and 3,330 (NH 2 ) (Nikravan, Haddadi‐Asl, & Salami‐Kalajahi, ). …”

A Comprehensive Outlook of Synthetic Strategies and Applications of Redox‐Responsive Nanogels in Drug Delivery

“…[29,[175][176][177][178][179][180][181] Dual stimuli-responsive nanogels generally involve a combination of redox-responsive cross-linkers and pH-responsive polymeric matrix as important nanogel constituents. Some of the important examples of pH-responsive polymers are polyacrylamide (PAAm), [182][183][184] poly(acrylic acid) (PAA), [72,185,186] PMAA, [182,[187][188][189][190] poly(2-diethylaminoethyl methacrylate) (PDEAEMA), [191,192] polyethyleneimine, [193][194][195] poly(l-lysine), [196,197] poly(2-vinyl pyridine) (P2VP), [198] poly(Nvinylamine) (PVAm), [199] poly(4-vinyl pyridine) (P4VP), [200,201] and chitosan. [184,202] The pH-and redox-responsive nanogels hold excellent potential and play a diverse role for targeted intracellular release of drugs due to their multidimensional role in response to variation in GSH concentration and pH inside the cellular compartment.…”