Exploring dendrimer towards dual drug delivery: pH responsive simultaneous drug-release kinetics

Abstract

A major problem associated with conventional leukaemia chemotherapy is the development of resistance that can be surmounted well by combination chemotherapy. The objective of the present investigation is to report a novel technology to load two anti-leukaemic drugs of choice simultaneously inside the PAMAM dendrimer. Under optimized conditions of pH and dialysis time, one molecule of PAMAM dendrimer was found to be capable of entrapping 27.02 ± 0.51 and 8.00 ± 0.46 molecules of Methotrexate and all-trans Retinoic acid (ATRA), respectively. The simultaneous in-vitro release profiling of the loaded drugs was studied at pH 4, 7.4 and 10. The release kinetics was found to be governed by degree of dendrimer protonation, with more sustained and controlled behaviour at pH 7.4. Terminal loading of dendrimer with less haemolytic bioactive (ATRA) reduced the haemolytic toxicity of the dendrimer formulation. A cytotoxicity study was performed on HeLa cell lines by MTT assay, wherein after 72 h, the dual-drug loaded dendrimer was found to be more efficient (IC(50) 0.5 µM) as compared to that of the free drug combination (IC(50) 0.75 µM).

Dendrimer, Liposomes, Carbon Nanotubes and PLGA Nanoparticles: One Platform Assessment of Drug Delivery Potential

“…In the current scenario, different nanocarriers like liposomes, nanoparticles, dendrimers, and carbon nanotubes are hot topics of explorations in lab throughout the globe (1,2,4-6,8-11) including our lab (12,20,21,23,25,(28)(29)(30)34,(36)(37)(38)(39)(40)(41), and are believed to revolutionize the field of biomedicine. In this line, allied reports on various formulation aspects of these nanocarriers (like size, loading efficacy, release kinetics, hemolytic toxicity, drug delivery potential, tumor localization, etc.)…”

“…Hemolytic toxicity of all the developed formulations was assessed under similar experimental condition by employing previously reported methodology, with slight modification in procedure (36)(37)(38). Briefly, whole human blood was collected in hiclot anti-vial (HiMedia, Mumbai, India) and centrifuged to collect red blood corpuscles (RBCs).…”

“…The MTT cytotoxicity assay determines the ability of viable cells to convert a soluble tetrazolium salt [3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) into an insoluble formazan precipitate (20,37,38). The MTT cytotoxicity assay was performed on human SiHa cell lines.…”

Nano drug delivery in oral cancer therapy: An emerging avenue to unveil

“…[7,8] Owing to their branching nature, Tekade et al, had co-encapsulated methotrexate (a hydrophobic anticancer drug) and all-trans retinoic acid (a hydrophilic agent with mild anticancer activity) in 5 poly(propyleneimine) dendrimer and reported that this conjugation was effective than free drug delivery when performed on HeLa cell lines. [7,33] …”

Dendrimers as therapeutic agents: a systematic review

“…This study was the first to report the simultaneous targeting of pro-inflammatory mediators and neoangiogenesis by dendrimers, with the capability of preventing scar tissue formation with higher levels of safety following surgery. [22] These therapeutic effects of dendrimers, coupled with their nanoscopic size, low polydispersity, ease of synthesis and stability, [106][107][108][109][110] demand their further scientific exploration.…”