l-Cysteine conjugated polyl-lactide nanoparticles containing 5-fluorouracil: formulation, characterization, release and uptake by tissuesin vivo

Abstract

Context: Targeted delivery of drugs is still a therapeutic challenge and numerous methods have been reported for the same. Objective: In this study, emphasis was placed on developing nanoparticles loaded with 5-fluorouracil (FU) and modifying the surface of the nanoparticles by conjugation with amino acid, to improve the distribution of 5-FU in the lungs. Methods: An emulsion solvent evaporation technique was used to formulate nanoparticles of FU using Poly L-lactide and Pluronic F-68. The nanoparticles were conjugated with L-Cysteine using EDC as the activator of COOH group and were evaluated for product yield, particle size, surface morphology, amount of conjugation by Ellman's method and in vitro drug release study. Results and conclusion: The results indicated 60-65% yield with an average particle size of 242.7 ± 37.11 nm for the cysteine conjugated nanoparticle (CNP) formulation and more than 70% conjugation of cysteine. The cumulative percentage of drug released over a period of 24 h was found to be 58%. An increase in distribution of the delivery system in lungs (11.4% ID after 1 h) in mice was found indicating the role of L-Cysteine in the transport mechanism to the lungs. In vivo kinetic studies in rats revealed higher circulation time of CNP as compared to pure FU solution. The study helps in designing a colloidal delivery system for increased distribution of drugs to the lungs and may be helpful in delivery of drugs in conditions like non-small cell lung carcinomas.

Radiation‐Sensitive Dendrimer‐Based Drug Delivery System

“…G4.5 dendrimers are characterized by C=O stretching vibrations (1650 cm −1 ), NH stretching (3272 cm −1 ), and NH bending (1570 cm −1 ). As activated carboxyl groups reacted with amino groups of l ‐Cys, forming amide bonds,36 C=O stretching, NH bending, and NH stretching peaks were slightly shifted. Additionally, S—H stretching vibration of l ‐Cys (intense absorption at 2550 cm −1 )37 was absent in GC, indicating formation of disulfide bonds, with Raman bands in the fingerprint region (strong sharp band near 500 cm −1 )38 supporting this finding (Figure 1C).…”

Targeted delivery of etoposide to cancer cells by folate-modified nanostructured lipid drug delivery system

“…The CT26, SGC7901 and NCI-H209 cells were treated with FA-ETP-NLCs, ETP-NLCs, ETP solution and NLCs, respectively (Mishra et al, 2015). The cells were seeded in a 96-well plate and allowed to adhere for 24 h prior to the assay.…”

“…Surface charge is an important indication for the structure and stability of nanoparticle system. The positive charged particle surfaces could have a higher binding affinity toward the negatively charged cell surfaces (Mishra et al, 2015).…”

An alternative choice of lidocaine-loaded liposomes: lidocaine-loaded lipid–polymer hybrid nanoparticles for local anesthetic therapy

“…The air-dried samples were then directly examined under the transmission electron microscopy (TEM, JEM-1200EX; JEOL Ltd., Tokyo, Japan) (Mishra et al, 2015).…”