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Nanomaterials in Chemotherapy
Published in D. Sakthi Kumar, Aswathy Ravindran Girija, Bionanotechnology in Cancer, 2023
P. K. Hashim, Anjaneyulu Dirisala
Dendrimers are unimolecular, highly branched, and three-dimensional polymers (Figure 8.7), which can be synthesized from monomeric units by adding new branches in a step-by-step manner until a uniform tree-like structure is formed. Depending on the branching architecture, one can design perfect dendrimers, dendrons, dendronized polymers, and hyperbranched polymers. A typical dendrimer possesses unique nanoarchitecture with an average diameter of 1–10 nm, low viscosity, high solubility, high surface functionality, and biocompatibility. Due to the presence of active termini on its surface, easy functionalization is possible in dendrimers. In comparison to linear polymers, dendritic polymer architecture is advantageous for drug delivery applications [162]. For example, due to its defined multivalency and drug conjugation, the addition of targeting ligand and/or solubilizing modalities can be incorporated in a single dendrimer. Dendrimer-based drug carriers showed extended circulation time and altered biodistribution profiles compared to bare drugs in preclinical animal models.
Recent Developments in Bioresponsive Drug Delivery Systems
Published in Deepa H. Patel, Bioresponsive Polymers, 2020
Drashti Pathak, Deepa H. Patel
Hydrogels have also evolved over the years through several generations wherein increased conferred functionality, control of polymer architecture and improved processing has enabled new and innovative applications resulting in the moniker of “smart materials.” Among these smart applications is one wherein the ability to sense and react with a biological entity is integrated with the physicochemical responses of the hydrogel.
PEGylated Dendritic Nanoparticulate Carriers of Anti-Cancer Drugs
Published in Mansoor M. Amiji, Nanotechnology for Cancer Therapy, 2006
D. Bhadra, S. Bhadra, N. K. Jain
The group of evaluated polymers was designed to include a range of MWs (from 20,000 to 160,000) and architectures with the number of PEO arms ranging from two to eight. In vitro experiments revealed that the polymers were non-toxic to cells and were degraded to lower MW species at pH 7.4 and pH 5.0. Biodistribution studies with 125I-radiolabeled polymers showed that the high MW carriers (> 40,000) exhibited long circulation half-lives. Comparison of the renal clearances for the four-arm versus eight-arm polymers indicated that the more branched polymers were excreted more slowly into the urine, a result attributed to their decreased flexibility. Because of their essentially linear architecture that does not provide for good isolation of the iodinated phenolic moieties, the polymers with two arms were rapidly taken up by the liver. The biodistributions of two long-circulating high MW polymers in mice bearing subcutaneous B16F10 tumors were evaluated, and high levels of tumor accumulation were observed. These new carriers are promising for applications in drug delivery and are also useful for improving the understanding of the effect of polymer architecture on pharmacokinetic properties (Elizabeth et al. 2005).
An overview of PLGA in-situ forming implants based on solvent exchange technique: effect of formulation components and characterization
Published in Pharmaceutical Development and Technology, 2021
Tarek Metwally Ibrahim, Nagia Ahmed El-Megrab, Hanan Mohammed El-Nahas
In the case of parenteral preparations, FDA states that the qualitative (Q1) and quantitative (Q2) composition of the test and reference products should be similar and the product copies should satisfy the Q1/Q2 sameness to be authorized with the Abbreviated New Drug Application (ANDA) (Hua et al. 2021). For example, the in-vitro and in-vivo performance of the polymeric PLGA-based products can be significantly influenced by the alterations in the manufacturing process in addition to the changes in the chemical properties of PLGA polymer regarding its composition, molecular weight and end-capping. This can result in major changes in the biopharmaceutical properties and bioavailability of the proposed drug. Given the complexity of this context, FDA requires a complete characterization of PLGA polymer to fulfill the Q1/Q2 requirements by the comparison of polymer composition, molecular weight distribution and polymer architecture (Zhou et al. 2018). After the marketing authorization, the marketed product may introduce some changes or adverse outcomes that clearly may lead to alterations in the quality, safety and efficacy of the drug. Therefore, several procedures including continuous clinical study analyses in patients should be followed by the manufacturer to ensure the maintenance of positive long-term performance and safety of the product (FDA 2016, 2018b).
Synthetic biodegradable polyesters for implantable controlled-release devices
Published in Expert Opinion on Drug Delivery, 2022
Jinal U. Pothupitiya, Christy Zheng, W. Mark Saltzman
Synthetic biodegradable polyesters are extensively used to manufacture biomedical implants that provide sustained drug release, including implants that have been approved by the US FDA for use in humans. Among the synthetic polyesters available, aliphatic polyesters such as polylactide (PLA), polyglycolide (PGA), polycaprolactone (PCL), polyvalerolactone (PVL), polydioxanone (PDO), and poly(lactide-co-glycolide) (PLGA) have received the most attention, although copolymers of pentadecalatone and dioxanone – poly(PDL-co-DO) – have also been used [33–35]. Degradation of these polymers occurs via hydrolytic cleavage of the ester backbone, and their degradation products are generally excreted through natural metabolic pathways [36]. Degradation rates of these polyesters can be tuned by manipulating the polymer architecture to promote faster or slower degradation kinetics, often by shifting the ratio of hydrophilic to hydrophobic co-monomers. Commercial availability and simple but controlled synthetic methods to produce these polymers make them attractive as candidates. The ease of processing a variety of copolymer compositions, molecular weight, and polymer architectures increase their utility in different applications. Here, we review the properties of synthetic polyesters that are most commonly used for biodegradable implants. Physical and chemical properties of these polyesters are summarized in Table 1. Examples of polyesters used for clinically tested controlled drug delivery applications, as compared to some other degradable polymers, are shown in Table 2.
A biocompatible reverse thermoresponsive polymer for ocular drug delivery
Published in Drug Delivery, 2019
Asitha Balachandra, Elsa C. Chan, Joseph P. Paul, Sze Ng, Vicki Chrysostomou, Steven Ngo, Roshan Mayadunne, Peter van Wijngaarden
While the high initial burst release of bevacizumab can be beneficial in ocular drug release, allowing for rapid increase of intravitreal drug concentration to a therapeutic level, depletion of the drug in the matrix is a potential concern. Nevertheless, if the rate of release of the drug from the polymer gel during the degradation phase can counteract the natural rate of removal of the drug from the eye, the current profile would, in principle, be well suited for drug delivery in vivo. Achieving a higher initial drug loading, together with an increase in the hydrophilicity of the polymer matrix, through changes to the polymer architecture or additives, would be needed to minimize burst release and prolong the window of release in vivo.