FDA’s Poly (Lactic-Co-Glycolic Acid) Research Program and Regulatory Outcomes

Wang, Yan; Qin, Bin; Xia, Grace; Choi, Stephanie

doi:10.1208/s12248-021-00611-y

Cited by 101 publications

(50 citation statements)

References 18 publications

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“…Interestingly, acidic poly ( d,l -lactide-co-glycolide) (PLGA) nanoparticles, which constitute a family of FDA-approved biodegradable polymers synthesized from glycolic acid and lactic acid, have long been studied as delivery vehicles for a variety of drugs, proteins and other macromolecules. In fact, some earlier studies have shown that PLGA-encapsulated drugs/agents such as donepezil, memantine etc., can have beneficial effects on cellular and/or animal models of AD with satisfactory biocompatibility [ 36 – 41 ]. More recently, we reported that PLGA nanoparticles without functionalization with any agent/drug can suppress Aβ aggregation/toxicity in cellular and animal models of AD [ 42 , 43 ].…”

Section: Introductionmentioning

confidence: 99%

Unconjugated PLGA nanoparticles attenuate temperature-dependent β-amyloid aggregation and protect neurons against toxicity: implications for Alzheimer’s disease pathology

Paul

Cho

et al. 2022

J Nanobiotechnol

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Conversion of β-amyloid (Aβ) peptides from soluble random-coil to aggregated protein enriched with β-sheet-rich intermediates has been suggested to play a role in the degeneration of neurons and development of Alzheimer’s disease (AD) pathology. Aggregation of Aβ peptide can be prompted by a variety of environmental factors including temperature which can influence disease pathogenesis. Recently, we reported that FDA-approved unconjugated poly (d,l-lactide-co-glycolide) (PLGA) nanoparticles can have beneficial effects in cellular and animal models of AD by targeting different facets of the Aβ axis. In this study, using biochemical, structural and spectroscopic analyses, we evaluated the effects of native PLGA on temperature-dependent Aβ aggregation and its ability to protect cultured neurons from degeneration. Our results show that the rate of spontaneous Aβ1–42 aggregation increases with a rise in temperature from 27 to 40 °C and PLGA with 50:50 resomer potently inhibits Aβ aggregation at all temperatures, but the effect is more profound at 27 °C than at 40 °C. It appears that native PLGA, by interacting with the hydrophobic domain of Aβ1–42, prevents a conformational shift towards β-sheet structure, thus precluding the formation of Aβ aggregates. Additionally, PLGA triggers disassembly of matured Aβ1–42 fibers at a faster rate at 40 °C than at 27 °C. PLGA-treated Aβ samples can significantly enhance viability of cortical cultured neurons compared to neurons treated with Aβ alone by attenuating phosphorylation of tau protein. Injection of native PLGA is found to influence the breakdown/clearance of Aβ peptide in the brain. Collectively, these results suggest that PLGA nanoparticles can inhibit Aβ aggregation and trigger disassembly of Aβ aggregates at temperatures outside the physiological range and can protect neurons against Aβ-mediated toxicity thus validating its unique therapeutic potential in the treatment of AD pathology. Graphical Abstract

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Section: Introductionmentioning

confidence: 99%

Unconjugated PLGA nanoparticles attenuate temperature-dependent β-amyloid aggregation and protect neurons against toxicity: implications for Alzheimer’s disease pathology

Paul

Cho

et al. 2022

J Nanobiotechnol

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“…To assist the generic pharmaceutical companies in their ANDA application, the FDA publishes product-specific guidance (PSG) describing the Agency’s expectations on the development of generic drug products that are therapeutically equivalent to a specific RLD [ 22 ]. The PSG contain information about the recommended bioequivalence studies, dissolution test methods, sampling times, expectations and evidence that are required to support the ANDA approval.…”

Section: Complexity In Developing Generic Plga-based Lai Drug Productsmentioning

confidence: 99%

Challenges and Complications of Poly(lactic-co-glycolic acid)-Based Long-Acting Drug Product Development

Lim

Tan

et al. 2022

Pharmaceutics

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Poly(lactic-co-glycolic acid) (PLGA) is one of the preferred polymeric inactive ingredients for long-acting parenteral drug products that are constituted of complex formulations. Despite over 30 years of use, there are still many challenges faced by researchers in formulation-related aspects pertaining to drug loading and release. Until now, PLGA-based complex generic drug products have not been successfully developed. The complexity in developing these generic drug products is not just due to their complex formulation, but also to the manufacturing process of the listed reference drugs that involve PLGA. The composition and product attributes of commercial PLGA formulations vary with the drugs and their intended applications. The lack of standard compendial methods for in vitro release studies hinders generic pharmaceutical companies in their efforts to develop PLGA-based complex generic drug products. In this review, we discuss the challenges faced in developing PLGA-based long-acting injectable/implantable (LAI) drug products; hurdles that are associated with drug loading and release that are dictated by the physicochemical properties of PLGA and product manufacturing processes. Approaches to overcome these challenges and hurdles are highlighted specifically with respect to drug encapsulation and release.

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“…This polymer presents many advantages, most especially its biocompatibility. Other benefits include its adequate rate of biodegradation and the production of non-toxic biodegradation products; the approval by the Food and Drug Administration (FDA) of more than 20 PLGA-based pharmaceutical products to date [82]; and the potential to modify surface properties to provide better interaction with biological materials [83]. Sadeghi-Avalshahr et al [64] used PLGA to produce electrospun nanofibers, which are characterized by high hydrophobicity.…”

Section: Poly(lactic-co-glycolic Acids) (Plga)mentioning

confidence: 99%

Electrospun Fibers Loaded with Natural Bioactive Compounds as a Biomedical System for Skin Burn Treatment. A Review

2021

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Burns are a major threat to public health and the economy due to their costly and laborious treatment and high susceptibility to infection. Efforts have been made recently to investigate natural bioactive compounds with potential use in wound healing. The importance lies in the capacities that these compounds could possess both in infection control by common and resistant microorganisms, as well as in the regeneration of the affected tissues, having in both cases low adverse effects. However, some bioactive molecules are chemically unstable, poorly soluble, and susceptible to oxidative degradation or have low bioavailability. Therefore, developing new technologies for an efficient treatment of wound healing poses a real challenge. In this context, electrospun nanofibers have gained increasing research interest because bioactive molecules can be easily loaded within the nanofiber, resulting in optimal burst control and enhanced drug stability. Additionally, the nanofibers can mimic the extracellular collagen matrix, providing a suitable highly porous structural support for growing cells that facilitate and accelerate skin burns healing. This review gives an overview of the current state of electrospun fibers loaded with natural bioactive compounds as a biomedical system for skin burn treatment.

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FDA’s Poly (Lactic-Co-Glycolic Acid) Research Program and Regulatory Outcomes

Cited by 101 publications

References 18 publications

Unconjugated PLGA nanoparticles attenuate temperature-dependent β-amyloid aggregation and protect neurons against toxicity: implications for Alzheimer’s disease pathology

Unconjugated PLGA nanoparticles attenuate temperature-dependent β-amyloid aggregation and protect neurons against toxicity: implications for Alzheimer’s disease pathology

Challenges and Complications of Poly(lactic-co-glycolic acid)-Based Long-Acting Drug Product Development

Electrospun Fibers Loaded with Natural Bioactive Compounds as a Biomedical System for Skin Burn Treatment. A Review

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