Building the design, translation and development principles of polymeric nanomedicines using the case of clinically advanced poly(lactide(glycolide))–poly(ethylene glycol) nanotechnology as a model: An industrial viewpoint

Lakkireddy, Harivardhan Reddy; Bazile, Didier

doi:10.1016/j.addr.2016.08.012

Cited by 33 publications

(24 citation statements)

References 380 publications

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“…Modulation of cellular uptake, extracellular transport and intracellular drug delivery is achieved by tuning size, shape, surface chemistry, antimicrobials’ intrinsic properties and microenvironments that PNs need to overstep. Targeting can be passive, activated by ligands attached to the outermost nanoparticle surface and drug release by natural ways or triggered by an external or internal stimulus [ 45 , 51 , 52 ].…”

Section: Polymeric Nanocarriers Against Intracellular Infections: mentioning

confidence: 99%

Recent Advances in Polymeric Nanoparticle-Encapsulated Drugs against Intracellular Infections

2020

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Polymeric nanocarriers (PNs) have demonstrated to be a promising alternative to treat intracellular infections. They have outstanding performance in delivering antimicrobials intracellularly to reach an adequate dose level and improve their therapeutic efficacy. PNs offer opportunities for preventing unwanted drug interactions and degradation before reaching the target cell of tissue and thus decreasing the development of resistance in microorganisms. The use of PNs has the potential to reduce the dose and adverse side effects, providing better efficiency and effectiveness of therapeutic regimens, especially in drugs having high toxicity, low solubility in the physiological environment and low bioavailability. This review provides an overview of nanoparticles made of different polymeric precursors and the main methodologies to nanofabricate platforms of tuned physicochemical and morphological properties and surface chemistry for controlled release of antimicrobials in the target. It highlights the versatility of these nanosystems and their challenges and opportunities to deliver antimicrobial drugs to treat intracellular infections and mentions nanotoxicology aspects and future outlooks.

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Section: Polymeric Nanocarriers Against Intracellular Infections: mentioning

confidence: 99%

Recent Advances in Polymeric Nanoparticle-Encapsulated Drugs against Intracellular Infections

2020

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“…[1][2][3][4][5][6][7][8][9][10] Their applications span a wide field, ranging from green wrapping materials and fibres [11][12][13] to surgical polymers, tissue engineering, drug delivery and other biomedical applications. 5,[14][15][16][17][18] The most frequently used biomedical polymers comprise homo-and copolymers of poly(lactic acid) (PLA), poly(glycolic acid) (PGA) and poly-(ε-caprolactone) (PCL). [19][20][21][22][23][24] Their synthesis via ringopening polymerization (ROP) is most commonly conducted with tin(II) 2-ethylhexanoate Sn(Oct) 2 .…”

Section: Introductionmentioning

confidence: 99%

Mono-BHT heteroleptic magnesium complexes: synthesis, molecular structure and catalytic behavior in the ring-opening polymerization of cyclic esters

et al. 2017

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Numerous heteroleptic 2,6-di-tert-butyl-4-methylphenolate (BHT) magnesium complexes have been synthesized by treatment of (BHT)MgBu(THF) with various alcohols. Molecular structures of the complexes have been determined by X-ray diffraction. The magnesium coordination number in [(BHT)Mg(μ-OBn)(THF)] (3) and [(BHT)Mg(μ-O-tert-BuCH)(THF)] (4) is equal to 4. Complexes formed from esters of glycolic and lactic acids, [(BHT)Mg(μ-OCHCOOEt)(THF)] (5) and [(BHT)Mg(μ-OCH(CH)COOCHCOOBu)(THF)] (6) contain chelate fragments with pentacoordinated magnesium. Compounds 3-6 contain THF molecules coordinated to magnesium atoms. Complex {(BHT)Mg[μ-O(CH)CON(CH)]} (7) does not demonstrate any tendency to form an adduct with THF. It has been experimentally determined that complexes 3 and 5 are highly active catalysts of lactide polymerization. The activity of 4 is rather low, and complex 7 demonstrates moderate productivity. According to DOSY NMR experiments, compounds 3 and 5 retain their dimeric structures even in THF. The free energies of model dimeric [(DBP)Mg(μ-OMe)(Sub)] and monomeric (DBP)Mg(OMe)(Sub) products on treatment of [(DBP)Mg(μ-OMe)(THF)] with a series of σ-electron donors (Sub) have been estimated by DFT calculations. These results demonstrate that the substitution of THF by Sub in a dimeric molecule is an energetically allowed process, whereas the dissociation of dimers is energetically unfavorable. DFT modeling of ε-CL and (dl)-lactide ROP catalyzed by dimeric and monomeric complexes showed that a cooperative effect of two magnesium atoms occurs within the ROP for binuclear catalytic species. A comparison of the reaction profiles for ROP catalyzed by binuclear and mononuclear species allowed us to conclude that the binuclear mechanism is favorable in early stages of ROP initiated by dimers 3 and 5.

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“…Since the 1970s, the use of polymeric NP formulations has rapidly expanded [85]. Polymers offer greater stability, more control over structure and drug loading, increased opportunities for high-throughput synthesis compared to lipid-based systems and better quality control.…”

Section: Polymersmentioning

confidence: 99%

“…Subtle differences in architectures and the physicochemical properties of the NP complexes (i.e. size, stiffness, surface potential, morphology, hydrophobicity) [112,113] can have significant effects on the in vitro and in vivo delivery efficiency [85]. Thus polymer composition should be carefully considered when designing such delivery vehicles.…”

Section: Polymersmentioning

confidence: 99%

Polymers in the Delivery of siRNA for the Treatment of Virus Infections

2017

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Viral diseases remain a major cause of death worldwide. Despite advances in vaccine and antiviral drug technology, each year over three million people die from a range of viral infections. Predominant viruses include human immunodeficiency virus, hepatitis viruses, and gastrointestinal and respiratory viruses. Now more than ever, robust, easily mobilised and cost-effective antiviral strategies are needed to combat both known and emerging disease threats. RNA interference and small interfering (si)RNAs were initially hailed as a "magic bullet", due to their ability to inhibit the synthesis of any protein via the degradation of its complementary messenger RNA sequence. Of particular interest was the potential for attenuating viral mRNAs contributing to the pathogenesis of disease that were not able to be targeted by vaccines or antiviral drugs. However, it was soon discovered that delivery of active siRNA molecules to the infection site in vivo was considerably more difficult than anticipated, due to a number of physiological barriers in the body. This spurred a new wave of investigation into nucleic acid delivery vehicles which could facilitate safe, targeted and effective administration of the siRNA as therapy. Amongst these, cationic polymer delivery vehicles have emerged as a promising candidate as they are low-cost and easy to produce at an industrial scale, and bind to the siRNA by non-specific electrostatic interactions. These nanoparticles (NPs) can be functionally designed to target the infection site, improve uptake in infected cells, release the siRNA inside the endosome and facilitate delivery into the cell cytoplasm. They may also have the added benefit of acting as adjuvants. This chapter provides a background around problems associated with the translation of siRNA as antiviral treatments, reviews the progress made in nucleic acid therapeutics and discusses current methods and progress in overcoming these challenges. It also addresses the importance of combining physicochemical characterisation of the NPs with in vitro and in vivo data.

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Building the design, translation and development principles of polymeric nanomedicines using the case of clinically advanced poly(lactide(glycolide))–poly(ethylene glycol) nanotechnology as a model: An industrial viewpoint

Cited by 33 publications

References 380 publications

Recent Advances in Polymeric Nanoparticle-Encapsulated Drugs against Intracellular Infections

Recent Advances in Polymeric Nanoparticle-Encapsulated Drugs against Intracellular Infections

Mono-BHT heteroleptic magnesium complexes: synthesis, molecular structure and catalytic behavior in the ring-opening polymerization of cyclic esters

Polymers in the Delivery of siRNA for the Treatment of Virus Infections

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