Covalent Polymer-Drug Conjugates

Elvira, Carlos; Gallardo, Alberto; Román, Julio San; Cifuentes, Alejandro

doi:10.3390/10010114

Cited by 102 publications

(51 citation statements)

References 32 publications

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“…Controlled drug delivery systems have now been developed to the point where they can facilitate site-specific delivery at precisely controlled rates [4][5][6][7][8][9]. Control over the delivery rate minimizes the toxicity and side effects of the drug being delivered [1,[10][11][12][13][14][15]. In order for a drug delivery system to provide a therapeutic payload with the maximum therapeutic benefit, the release profile of new drug delivery systems typically need to be carefully adapted to the particular application.…”

mentioning

confidence: 99%

Controlled Drug Delivery From Composites of Nanostructured Porous Silicon and Poly( L -Lactide)

et al. 2012

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Aims: Porous silicon (pSi) and poly(L-lactide) (PLLA) both display good biocompatibility and tunable degradation behavior, suggesting that composites of both materials are suitable candidates as biomaterials for localized drug delivery into the human body. The combination of a pliable and soft polymeric material with a hard inorganic porous material of high drug loading capacity may engender improved control over degradation and drug release profiles and be beneficial for the preparation of advanced drug delivery devices and biodegradable implants or scaffolds. Materials & methods: In this work, three different pSi and PLLA composite formats were prepared. The first format involved grafting PLLA from pSi films via surface-initiated ring-opening polymerization (pSi–PLLA [grafted]). The second format involved spin coating a PLLA solution onto oxidized pSi films (pSi–PLLA [spin-coated]) and the third format consisted of a melt-cast PLLA monolith containing dispersed pSi microparticles (pSi–PLLA [monoliths]). The surface characterization of these composites was performed via infrared spectroscopy, scanning electron microscopy, atomic force microscopy and water contact angle measurements. The composite materials were loaded with a model cytotoxic drug, camptothecin (CPT). Drug release from the composites was monitored via fluorimetry and the release profiles of CPT showed distinct characteristics for each of the composites studied. Results: In some cases, controlled CPT release was observed for more than 5 days. The PLLA spin coat on pSi and the PLLA monolith containing pSi microparticles both released a CPT payload in accordance with the Higuchi and Ritger–Peppas release models. Composite materials were also brought into contact with human lens epithelial cells to determine the extent of cytotoxicity. Conclusion: We observed that all the CPT containing materials were highly efficient at releasing bioactive CPT, based on the cytotoxicity data. Original submitted 16 December 2010; Revised submitted 29 September 2011; Published online 6 March 2012

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confidence: 99%

Controlled Drug Delivery From Composites of Nanostructured Porous Silicon and Poly( L -Lactide)

et al. 2012

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“…The generation of protein conjugates, e.g., proteins equipped with functional groups such as fluorescent molecules and affinity tags, or proteins linked to drugs and other proteins, is of special interest for many biophysical, biotechnological and biomedical applications [92,93]. For instance, there is a great interest in the generation of potent antibody-drug conjugates, which facilitate the targeting of cytotoxic payloads to cancer cells, ideally leading to reduced side effects and an enlarged therapeutic window of the chemotherapeutic reagent.…”

Section: Scfv Fusion Proteinsmentioning

confidence: 99%

Cell-Free Synthesis Meets Antibody Production: A Review

Stech

Kubick

2015

Antibodies

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Engineered antibodies are key players in therapy, diagnostics and research. In addition to full size immunoglobulin gamma (IgG) molecules, smaller formats of recombinant antibodies, such as single-chain variable fragments (scFv) and antigen binding fragments (Fab), have emerged as promising alternatives since they possess different advantageous properties. Cell-based production technologies of antibodies and antibody fragments are well-established, allowing researchers to design and manufacture highly specific molecular recognition tools. However, as these technologies are accompanied by the drawbacks of being rather time-consuming and cost-intensive, efficient and powerful cell-free protein synthesis systems have been developed over the last decade as alternatives. So far, prokaryotic cell-free systems have been the focus of interest. Recently, eukaryotic in vitro translation systems have enriched the antibody production pipeline, as these systems are able to mimic the natural pathway of antibody synthesis in eukaryotic cells. This review aims to overview and summarize the advances made in the production of antibodies and antibody fragments in cell-free systems.

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“…Even for the development of IV formulations the water insoluble nature of paclitaxel causes trouble for development using aqueous solvents with painless administration. The research involving the conversion of paclitaxel into its prodrug form using conjugation with biopolymers or synthetic polymers wasexploited to achieve optimum therapeutic effect 3 .…”

Section: Introductionmentioning

confidence: 99%

Polyethylene Glycol Conjugates of Paclitaxel as Prodrugs by Simple Technique Such as Solvent Evaporation

Meghana¹,

Prabhakar²

2017

Int. Res. J. Pharm.

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Paclitaxel (PACL) is an anti-cancer drug used to treat breast cancer, lung cancer, ovarian cancer etc. It is available as IV infusion and not as oral formulation. It is practically insoluble in water and hence possesses problems for development as oral or per oral formulations. Hence in the present research work, polyethylene glycol conjugates of PACL were prepared by simple technique such as solvent evaporation technique using high molecular weight polyethylene glycols such as PEG15000 and PEG35000 without linking agents. Eight compositions in drug to PEG15000/PEG35000 ratio of (1:10), (1:20) (1:25) and (1:50) were prepared. The prepared conjugates were evaluated by solubility studies, drug content uniformity and analysis by FTIR and DSC. Solubility of paclitaxel was enhanced in case of all prepared PACL-PEG conjugates. PACL: PEG35000(1:50) exhibited 0.317±0.081 mg/ml and all other PACL: PEG35000 conjugates of ratios (1:10), (1:20) (1:25) and (1:50) also evidenced same values with slight variation.The low c.v. values in percent drug content values of all conjugates ensured the uniformity of drug in prepared conjugates. FTIR spectra of paclitaxel PACL:PEG35000 evidenced disappearance of -N-H vibrational stretch at 3311.35 cm -1 indicating conjugation of this end hydroxyl group with amine group of paclitaxel. The shift in the endothermic peak of the PEG conjugate (67.29 0 C) compared to the respective pure drug (221.57 0 C) confirmed the formation of drug-PEG conjugate. This work indicates PEG conjugates of paclitaxel will act as prodrugs and upon dissolution of polyethylene glycol moieties they parent drug in body fluids without effecting required therapeutic effect of paclitaxel.

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Covalent Polymer-Drug Conjugates

Cited by 102 publications

References 32 publications

Controlled Drug Delivery From Composites of Nanostructured Porous Silicon and Poly( L -Lactide)

Controlled Drug Delivery From Composites of Nanostructured Porous Silicon and Poly( L -Lactide)

Cell-Free Synthesis Meets Antibody Production: A Review

Polyethylene Glycol Conjugates of Paclitaxel as Prodrugs by Simple Technique Such as Solvent Evaporation

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