Green synthesis of methoxy-poly(ethylene glycol)-block-poly(<scp>l</scp>-lactide-co-glycolide) copolymer using zinc proline as a biocompatible initiator for irinotecan delivery to colon cancer in vivo

Giram, Prabhanjan S.; Wang, Julie; Walters, Adam A.; Rade, Priyanka P.; Akhtar, Muhammad; Han, Shunping; Faruqu, Farid N.; Abdel-Bar, Hend Mohamed; Garnaik, Baijayantimala; Al‐Jamal, Khuloud T.

doi:10.1039/d0bm01421d

Cited by 17 publications

(13 citation statements)

References 47 publications

(54 reference statements)

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“…The neutropenia side effect of Ir signi cantly reduced in Ir encapsulated P-DSPE-Ir/P-DSPE-PEG-Ir nanocarriers. In the literature our previous study report m-PEG-PLGA based nanoparticles with Tween-80 and Pluronics coating successfully used for pancreatic, colon cancer delivery-PEG-PLGA based nanoparticles shown better tumor growth delay and non-immunogenicity, biocompatibility [47]. In the present study Overall results, reported synthesis of PLGA and theire characterization and further well characterized for colonic delivery applications.…”

Section: Discussionsupporting

confidence: 56%

Irinotecan Loaded Lipomers: Development, And Characterization For Proof of Concept To Combat Colon Cancer

Giram

Garnaik

2021

Preprint

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PLGA Poly (lactide-co-Glycolide) is a biocompatible and biodegradable copolymer gained popularity for tissue engineering, drug delivery, biosensing, and biomedical applications. In the present study PLGA of (Mw =13,900) has synthesized by ring opening polymerization with zinc proline initiator. Irinotecan (Ir) loaded Lipomers (LPs) formulated with PLGA, DSPE-PEG (2000) (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino (polyethylene glycol)-2000) and soya lecithin excipients by nanoprecipitation method. These formulated LPs further validated by physicochemical and biological potential for colon delivery applications. The potential of LPs for delivery of Irinotecan (Ir), a poorly water-soluble chemotherapeutic drug used for the treatment of colon cancer was studied. LPs of controlled size (80-120 nm), surface charge (~ -35 mV), sustained release potential and significant cytotoxicity against CT-26 (colon) cancer cells, were successfully prepared. In-vivo biodistribution and tumor site retention in CT-26 xenografts tumor bearing Balb/C mice showed promising result for tumor uptake and retention for prolong time period. Unlike P-DSPE-Ir, PEG coated P-DSPE-PEG-Ir LPs exhibit significant tumor growth delay compared to untreated and blank formulation treated groups in the CT-26 subcutaneous tumor model, after 4 treatments of 10 mg Ir/kg dose. The biocompatibility, safety of LPs confirmed by acute toxicity study of optimized formulation. Overall, this proof-of-concept study demonstrates that the LPs improved efficacy, bioavailability and decreases neutropenia of Ir to combat colon cancer.

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Section: Discussionsupporting

confidence: 56%

Irinotecan Loaded Lipomers: Development, And Characterization For Proof of Concept To Combat Colon Cancer

Giram

Garnaik

2021

Preprint

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“…However, with the advent of biocompatibility and biodegradable polymers, the development of suitable polymer micellar drug delivery systems coupled with sustained drug release has made excellent carriers for antitumor drugs ( Gao et al, 2015 ; Tan L et al, 2017 ; Li et al, 2020 ; Lu et al, 2020 ; Chen et al, 2021 ). Moreover, self-assembly and passive targeting of EPR might contribute to a greater therapeutic effect ( Tan L et al, 2017 ; Lu et al, 2020 ; Li et al, 2020 ; Giram et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

mPEG-PDLLA Micelles Potentiate Docetaxel for Intraperitoneal Chemotherapy in Ovarian Cancer Peritoneal Metastasis

et al. 2022

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Ovarian cancer is the second most common cause of gynecological cancer death in women. It is usually diagnosed late and accompanied by peritoneal metastasis. For ovarian cancer with peritoneal metastasis, intraperitoneal (IP) chemotherapy can maintain a high drug concentration in the abdominal cavity and reduce local and systemic toxicity. Recently, docetaxel (DTX) has shown broad-spectrum antitumor activity against various malignant tumors, including ovarian cancer with peritoneal metastasis. However, DTX has limited clinical applications due to its poor water solubility, predisposition to hypersensitivity, fluid retention, and varying degrees of neurotoxicity. In this study, we prepared methoxy-poly(ethylene glycol)-block-poly(D,L-lactide) (mPEG-PDLLA) micelles loaded with DTX and developed an alternative, less toxic, more effective DTX formulation, without Tween 80, and evaluated its pharmacokinetics in the abdominal cavity and its efficacy in ovarian cancer with peritoneal metastasis. The mean diameter of DTX-mPEG-PDLLA was about 25 nm, and the pharmacokinetics of BALB/c mice via IP showed that the plasma exposure of DTX-mPEG-PDLLA was about four times lower than that of DTX. Importantly, DTX-mPEG-PDLLA was significantly more effective than DTX and prolonged the survival period in a SKOV-3 ovarian cancer peritoneal metastasis model. Moreover, the apoptosis rate was significantly increased in vitro. Based on these findings, it is expected that DTX-mPEG-PDLLA can enhance efficacy against ovarian cancer peritoneal metastasis, while reducing toxic side effects, and has the potential to be used in the clinical treatment of peritoneal metastatic cancer.

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“…To preserve the sink condition, 3 mL of test samples were withdrawn and replaced with fresh buffer at 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 h. Cellulose acetate syringe filters with a pore size 0.45 µm were used to filter each sample taken. 35 The concentration of EPL in IC and NP was measured at 388 nm wavelength using a UV-Vis spectrophotometer and analyzed using DD-Solver (Microsoft Add-In) software.…”

Section: Methodsmentioning

confidence: 99%

Enhanced Oral Bioavailability of Epalrestat SBE7-β-CD Complex Loaded Chitosan Nanoparticles: Preparation, Characterization and in-vivo Pharmacokinetic Evaluation

Alvi¹,

Akhtar²,

Mahmood³

et al. 2021

IJN

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Background Epalrestat (EPL) is a carboxylic acid derivative with poor aqueous solubility and its pharmacokinetic features are not fully defined. Purpose Current research aimed to fabricate inclusion complexation of EPL with SBE 7 β-CD (IC) and EPL/SBE 7 β-CD CS NPs (NP). Methods EPL was complexed with SBE 7 β-CD using the co-precipitation method, and the prepared complex was fabricated into nanoparticles using the ionic gelation method. The prepared formulations were characterized for particle size analysis, surface morphology, and in vitro dissolution study. The % inhibition of EPL against α-glucosidase enzyme was also conducted to check the drug’s antidiabetic activity. Finally, an in vivo pharmacokinetic investigation was carried out to determine the concentration of EPL in rabbit plasma of the prepared formulation. In vivo pharmacokinetic studies were conducted by giving a single dose of pure EPL, IC, and NP. Results The size of NP was found to be 241.5 nm with PDI 0.363 and zeta potential of +31.8 mV. The surface of the prepared NP was non-porous, smooth and spherical when compared with pure EPL, SBE 7 β-CD and IC. The cumulative drug release (%) from IC and NP was 73% and 88%, respectively, as compared to pure drug (25%). The % inhibition results for in vitro α-glucosidase was reported to be 74.1% and the predicted binding energy for in silico molecular docking was calculated to be −6.6 kcal/mol. The calculated C max values for EPL, IC and NP were 4.75±3.64, 66.91±7.58 and 84.27±6.91 μg/mL, respectively. The elimination half-life of EPL was 4 h and reduced to 2 h for IC and NP. The AUC 0-α for EPL, IC and NP were 191.5±164.63, 1054.23±161.77 and 1072.5±159.54 μg/mL*h, respectively. Conclusion Taking these parameters into consideration it can be concluded that IC and NP have prospective applications for greatly improved delivery and regulatedt release of poorly water soluble drugs, potentially leading to increase therapeutic efficacy and fewer side effects.

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Green synthesis of methoxy-poly(ethylene glycol)-block-poly(l-lactide-co-glycolide) copolymer using zinc proline as a biocompatible initiator for irinotecan delivery to colon cancer in vivo

Abstract: Green synthesis of mPEG–PLGA and nanoformulation for delivery of irinotecan to colon cancer.

Cited by 17 publications

References 47 publications

Irinotecan Loaded Lipomers: Development, And Characterization For Proof of Concept To Combat Colon Cancer

Irinotecan Loaded Lipomers: Development, And Characterization For Proof of Concept To Combat Colon Cancer

mPEG-PDLLA Micelles Potentiate Docetaxel for Intraperitoneal Chemotherapy in Ovarian Cancer Peritoneal Metastasis

Enhanced Oral Bioavailability of Epalrestat SBE7-β-CD Complex Loaded Chitosan Nanoparticles: Preparation, Characterization and in-vivo Pharmacokinetic Evaluation

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