Microencapsulation of nanoparticles with enhanced drug loading for pH‐sensitive oral drug delivery for the treatment of colon cancer

Abstract

Drug-delivery carriers must endure harsh pH conditions in the gastrointestinal tract and still maintain a high drug loading (DL) for oral therapeutic drugs to be effectively delivered to the colon area. In this research, a pH-sensitive drug-delivery system with an enhanced DL was developed by the coating of 5-fluorouracil (5-FU)-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) with Eudragit S100 with an oil-in-oil solvent evaporation technique. The enhanced DL and encapsulation efficiency were achieved by the optimization of the fabrication parameters and by the use of particles of a proper size. A DL of 5.8% was obtained by a moderate initial drug feeding, a high volume ratio of the outer water phase to the organic phase, and by the adjustment of the pH value of the outer aqueous phase to the isoelectric point of 5-FU. An in vitro drug-dissolution test showed that the coating of the Eudragit S100 microspheres could effectively prevent drugs from being released in an environment with a pH lower than 7. The PLGA NPs showed an initial burst release followed by a slow and sustained release over an extended period of over 120 h at pH value of 7.4. Therefore, the prepared systems have great potential for practical applications in the treatment of colorectal cancer.

Fabrication of high specificity hollow mesoporous silica nanoparticles assisted by Eudragit for targeted drug delivery

“…When the pH is decreased from 8.0 to 5.5, the release rate is accelerated and the total amount of 5-FU released increases. The net charge decreases [65] near the isoelectric point of 5-FU (pKa = 8.02). Thus, electrostatic attractions between the inorganic carrier and drug molecules are minimal.…”

“…Thus, electrostatic attractions between the inorganic carrier and drug molecules are minimal. However, at low pH (pH = 5.5) the elevated electrostatic repulsion leads to the higher transport of 5-FU through the mesoporous silica shell and thus a greater release rate and capacity [65]. The amount of 5-FU released from HMSNs in pH 8.0 and 5.5 PBS solutions is $38.0% and $44.0% at 25 h, respectively.…”

Targeted delivery of 5-fluorouracil to HT-29 cells using high efficient folic acid-conjugated nanoparticles

“…Formulation of PLGA-based nano-drug delivery carrier 5-FU loaded PLGA nanoparticles were fabricated by a modified W 1 /O/W 2 multiple emulsion and solvent evaporation technique (Wang et al, 2013b). Briefly, 100 mg of PLGA was dissolved in 6 mL methylene chloride (DCM).…”

PLGA Biodegradable Nanoparticles Containing Perphenazine or Chlorpromazine Hydrochloride: Effect of Formulation and Release

“…The PLGA polymer was also used for the nanoformulation of levofloxacin, for which the average size of NPs obtained for different conditions was 268 nm [ 10 ]. Using different pH and optimization methods of NPs, fabrications with theoretical drug loading ranged from 5% to 20% ( w / w ), the NPs of 5-fluorouracil in PLGA ( M W 15,000) sized in range 189.2 and 233.6 nm were obtained [ 11 ]. The process of praziquantel NPs formation using PLGA ( M W 40,000–100,000), with drug loading 10% to 30% ( w / w ) and emulsion formation, the particle sizes were obtained in a range of 250 to 340 nm [ 12 ].…”