Biodegradable Block Copolymers Research Articles

Diblock Copolymer Targeted Lipid Nanoparticles: Next-Generation Nucleic Acid Delivery System Produced by Confined Impinging Jet Mixers.

Despite the recent advances and clinical demonstration of lipid nanoparticles (LNPs) for therapeutic and prophylactic applications, the extrahepatic delivery of nucleic acids remains a significant challenge in the field. This limitation arises from the rapid desorption of lipid-PEG in the bloodstream and clearance to the liver, which hinders extrahepatic delivery. In response, we explore the substitution of lipid-PEG with biodegradable block copolymers (BCPs), specifically poly(ε-caprolactone)-block-poly(ethylene glycol) (PCL-b-PEG). BCPs offer strong anchoring for large macromolecules, potentially enhancing cell-specific targeting. To develop and optimize BCP-stabilized LNPs (BCP-LNPs), we employed a Design of Experiment (DOE) approach. Through a systematic exploration, we identified optimal formulations for BCP-LNPs, achieving desirable physicochemical properties and encapsulation efficiency. Notably, BCP-LNPs exhibit surprising trends in transfection efficiency, with certain formulations showing up to a 40-fold increase in transfection in Hela cells, while maintaining minimal cytotoxicity. The lipid compositions that optimized PCL-b-PEG LNP transfection were different from the compositions that optimized PEG-lipid LNP transfection. Furthermore, our study confirms the versatility of BCP-LNPs in encapsulating and delivering both mRNA and pDNA, demonstrating their cargo-agnostic nature. Lastly, we showcased the targeted BCP-LNPs using a Cetuximab-conjugated formulation. These targeted LNPs show significant promise in delivering cargo specific to EGFR-overexpressing cells (A549 cells), with up to 2.4 times higher transfection compared to nontargeted LNPs. This finding underscores the potential of BCP-LNPs in targeted gene therapy, especially in challenging scenarios such as tumor targeting. Overall, our study establishes the viability of BCP-LNPs as a versatile, efficient, and targeted delivery platform for nucleic acids, opening avenues for advanced therapeutic applications.

2D ZIF-L(Zn) for Hybrid Copolymerization of Methyl Methacrylate and ε-Caprolactone under Solvent-free Medium

Herein, we report the hybrid copolymerization of methyl methacrylate (MMA) and ε-caprolactone (CL). 2D metal-organic frameworks, ZIF-L as a robust polymerization catalyst, can catalyze this hybrid copolymerization. Though these monomers differ from each other in structure and activity, different characterization techniques (1H-NMR, 13C-NMR, GPC, DSC, fractional precipitation techniques) confirm that they form biodegradable block copolymer PMMA-b-PCL with high molecular weight (1190 kg/mol). Also, PXRD and SEM results of the recovered ZIF-L reveal that the catalyst ZIF-L is remarkably stable even after a long-time polymerization reaction with no significant loss in activity.

Achieving Long-Acting Local Analgesia Using an Intelligent Hydrogel Encapsulated with Drug and pH Regulator.

Local anesthetics are important for the treatment of postoperative pain. Since a single injection of the solution of a drug such as bupivacaine (BUP) works only for a few hours, it is much required to develop a long-term injectable formulation that maintains its efficacy for more than 1 day. Herein, an intelligent copolymer hydrogel loaded with BUP microcrystals was invented. The biodegradable block copolymer was synthesized by us and composed of a central hydrophilic poly(ethylene glycol) (PEG) block and two hydrophobic poly(lactide-co-glycolide) (PLGA) blocks. The aqueous system of the amphiphilic copolymer underwent a sol-gel transition between room temperature and body temperature and, thus, physically gelled after injection. Considering the decrease of solubility of BUP with the increase of pH and the internal acidic environment due to the hydrolysis of PLGA, calcium carbonate (CaCO3) powder was introduced as a pH regulator. Then, the internal pH was found to be nearly neutral and many BUP microcrystals were dispersed in the gel network. In this way, BUP had achieved a sustained release out of the thermogel. The maximum possible effect (MPE) in a rat sciatic nerve blockade model was used to describe the sensory blockade effect. In vivo analgesic effects evaluated with a hot plate experiment of rats demonstrated that the thermogel encapsulated with BUP microcrystal and CaCO3 powder significantly prolonged analgesia up to 44 h, the duration time with respect to 50% MPE. The intramuscularly injected implant exhibited biocompatibility in histological analyses. Besides, the untreated leg of the rats was not influenced by the treated leg, indicating no obvious systematic anesthesia of this hydrogel formulation. Such an intelligent and composite formulation represents a potential strategy for long-acting analgesia therapy.

A New Biodegradable Linear mPEG‐b‐poly(Schiff Base‐Acetal) Copolymer Carrier Co‐Delivery Cinnamaldehyde and Gemcitabine for Combined Anticancer Therapy

AbstractDue to significant pH difference among the healthy tissue, tumor tissue as well as intracellular endo/lysosome, constructing pH‐responsive biodegradable nanodrug delivery systems has received more and more attention. Herein, double‐end alkenylated acetal monomer (based on cinnamaldehyde (CA)) and double‐end sulfhydrylation Schiff base monomer were designed and synthesized, and three pH‐responsive biodegradable block copolymer mPEG‐b‐poly(Schiff base‐acetal) (P1), mPEG‐b‐poly(acetal) (P2), and mPEG‐b‐poly(Schiff base) (P3) were obtained by Michael addition reaction. All these polymers could be self‐assembled with gemcitabine (GEM) to form GEM‐loaded micelles. Proton nuclear magnetic resonance (1H NMR) and dynamic light scattering (DLS) experiments proved that these polymer micelles have good pH responsiveness. The size and morphology of both blank and GEM‐loaded micelles were characterized by DLS and scanning electron microscope (SEM). The GEM/P1, GEM/P2, and GEM/P3 micelles exhibited pH‐sensitive drug release properties and the GEM/P1 micelles has the relatively fastest drug release rate. Containing multiple acetal and Schiff base moieties GEM/P1 micelles showed fastest cellular internalized rate and best in vitro antitumor activity among all GEM‐loaded micelles.

Biodegradable block copolymer as compatibilizer and blend component of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)-based polyester blends

Atactic poly(3-hydroxybutyrate) (PHB)-b-poly(ε-caprolactone) (PCL) diblock copolymer, a type of biodegradable block copolymer (BCP) was selected as compatibilizer for poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBH)/PCL immiscible blends. The additive effect of BCP on the morphologies and mechanical properties was dependent on the blend composition of PHBH/PCL. For 80/20 (w/w) PHBH/PCL blends, the incorporation of BCP did alter their mechanical properties by the increase in elongation at break with increasing BCP amount. However, the addition of BCP for 60/40 (w/w) PHBH/PCL blends were not greatly affected on their morphologies and mechanical properties. When BCP was used as one of binary blend components, the mechanical properties were significantly changed depending on the blend composition. PHBH/BCP blends also showed promising improvement in terms of mechanical performance. Presence of BCP in the ternary and binary blend systems decreased the enzymatic degradation rate by PHB depolymerase.

Self-assembled biodegradable block copolymer precursors for the generation of nanoporous poly(trimethylene carbonate) thin films

Even though the domain of nanoporous template manufacturing from self-assembled block copolymers is in full expansion, challenging studies addressing innovative biodegradable block copolymer assemblies are still not reported. Herein, we address the usage of an original biodegradable precursor to prepare nanoporous thin films: the PTMC-b-PDLLA-b-PTMC triblock copolymer. The copolymer is designed to have a favorable interaction parameter for phase-separation, which was confirmed by differential scanning calorimetry by the appearance of two distinctive glass transition temperatures, corresponding to each of the blocks. Thin films are firstly produced by spin-coating and two methods are investigated for achieving organized self-assembly of the system: solvent evaporation and solvent vapor annealing. Well-organized bicontinuous nanoscopic phase-separated morphologies consisting of PTMC and PDLLA domains are achieved under precise solvent vapor annealing conditions for a particular triblock copolymer composition. Triblock copolymer self-assembly is compared to the one occurring in PTMC/PDLLA blends where no ordered phase-separation is observed. Moreover, thin films photo-crosslinking of previously methacrylated PTMC end-blocks, beneficial to the stability and cohesion of the PTMC phase, as well as mechanical strength of the porous matrix, proved to preserve the phase separation. From the optimal oriented block copolymer thin films, selective etching via PDLLA mild hydrolysis resulted in nanoporous PTMC with maintained long-range order and stability. Such approach to generate nanoporous PTMC could have great potential in both biomedical applications and the energy field.

Novel degradable amphiphilic 4-arm star PLA-b-POEOA and PLGA-b-POEOA block copolymers: synthesis, characterization and self-assembly

Well-defined amphiphilic biodegradable block copolymers (BCPs) are promising materials as drug/gene carriers because they can self-assemble in aqueous medium and form various nanostructures.

Dual drug delivery system of RAPTA-C and paclitaxel based on fructose coated nanoparticles for metastatic cancer treatment

Ruthenium complexes have been widely studied as potential alternatives to platinum-type anticancer drugs due to their unique medical properties such as high selectivity, strong ability to inhibit solid tumour metastasis. However, non-specific biodistribution, and weak lethality of ruthenium to cancer cells limit its use in medical application. Drug delivery systems offer the ability to integrate multiple drugs in one system, which is particularly important to enhance the chemotherapeutic efficacy and to potentially achieve a synergistic effect of both drugs. Here, we report a dual drug nanocarrier that is based on a self-assembled biodegradable block copolymer, where the ruthenium complex (RAPTA-C) is chemically attached to the polymer chain, while another drug, paclitaxel (PTX), is entrapped in the core of the micelle. The dual drug delivery system was studied via in vitro tests using MDA-MB-231 breast cancer cells and it was observed that RAPTA-C in combination with PTX significantly enhanced anti-tumour and anti-metastasis activity.

Scalable and Uniform Length-Tunable Biodegradable Block Copolymer Nanofibers with a Polycarbonate Core via Living Polymerization-Induced Crystallization-Driven Self-assembly.

Uniform 1D block copolymer (BCP) nanofibers prepared by the seeded-growth approach termed living crystallization-driven self-assembly (CDSA) offer promising potential for various applications due to their anisotropy, length tunability, and variable core and coronal chemistries. However, this procedure consists of a multi-step process involving independent BCP synthesis and self-assembly steps, where the latter is performed at low solution concentrations (<1 wt %), hindering scale-up. Here, we demonstrate the use of a one-pot BCP synthesis and self-assembly process, polymerization-induced CDSA (PI-CDSA), to access length-disperse nanofibers with a biodegradable crystalline poly(fluorenetrimethylenecarbonate) (PFTMC) core and a hydrophilic poly(ethylene glycol) (PEG) corona derived from PEG-b-PFTMC at concentrations up to 20 wt %, 400 times higher than those previously reported. Furthermore, living PI-CDSA could be used to access scalable, low dispersity, and length-tunable 1D PEG-b-PFTMC nanofibers at concentrations of up to 10 wt %. This provides the first example of living PI-CDSA involving an all-organic and biodegradable BCP that utilizes a conveniently implemented BCP synthesis protocol and does not involve living anionic polymerization. Significantly, samples of low-dispersity nanofibers of controlled lengths from 100 to 660 nm (Lw/Ln = 1.08-1.20) were prepared, allowing for upscaled access to well-defined biodegradable nanofibers at useful length-scales for applications in nanomedicine. Interestingly, detailed studies revealed a key role for PFTMC homopolymer impurities in the BCP prepared in situ in the formation of nanofibers under the reaction conditions used.

One-Pot Reactive Melt Recycling of PLA Post-Consumer Waste for the Production of Block Copolymer Nanocomposites of High Strength and Ductility.

Post-consumer waste recycling is a crucial issue for building a sustainable society. However, mechanical recycling of poly(lactic acid) (PLA) often reduces the performance of the recycled material because PLA has a strong tendency to degrade during reprocessing. Therefore, it is of great interest to develop an effective recycling method to improve the mechanical performance of this material. This paper presents a one-pot melt process for turning PLA waste into a biodegradable block copolymer and its high strength and ductility composite. The process was conducted in a melt-mixer through a transesterification of PLA with poly(ethylene glycol) (PEG) or poly(propylene glycol) (PPG) as a soft component and clay as reinforcement. Effects of soft component content and sequence of clay addition on the mechanical performance of the prepared materials were focused. The results showed the successful preparation of PLA-based multiblock copolymers of high molecular weights (~100 kDa). Both virgin PLA and recycled source could serve as the starting material. PEG was more efficient than PPG in providing an intense improvement of PLA ductility. The nanocomposite of intercalated structure yielded nearly 100 times higher elongation at break (Eb = 506%) than the starting PLA (Eb = 5.6%) with high strength of 39.5 MPa and modulus of 1.4 GPa, considering the advantages of clay addition. Furthermore, the products with a broadened range of properties can be designed based on the ratio of PLA and soft component, as well as the organization and spatial distribution of clay in the copolymer matrices.

Switchable Polymerization: A Practicable Strategy to Produce Biodegradable Block Copolymers with Diverse Properties.

With the global demand for sustainable development, there has been an increasing interest in using natural biomass as raw resources to produce sustainable polymers as an alternative to petroleum-based polymers. Because monocomponent biodegradable polymers are often insufficient in performance, copolymers with well-engineered block structures are synthesized to reach wide tunability. Switchable polymerization is such a practical strategy to produce biodegradable block copolymers with diverse performance. This review focus on the performance of block copolymers bearing biodegradable polymer segments produced by diverse switchable polymerization. We highlight two main segments that are critical for biodegradable block copolymers, i. e., polyester and polycarbonate, summarize the multiple characters of materials from switchable polymerization such as antibacterial, shape memory, adhesives, etc. The state-of-the-art research on biodegradable block copolymers, as well as an outlook on the preparation and application of novel materials, are presented.

Toughening Poly(l-lactide) Blends: Effectiveness of Sequence-Controlled Six-Arm Star-Branched Block Copolymers of Poly(l-lactide) and Poly(ε-caprolactone).

Well-defined six-arm star-branched bio-degradable block copolymers of l-lactide and ε-caprolactone were prepared using controlled ring-opening polymerization and a sequential monomer addition method using dipentaerythritol as the initiator core and organocatalysts at low temperatures in solution. Sequence of enchainment was changed by reversing the order of monomer addition giving, either, a crystalline PLA block or an amorphous PCL block as the outer segment. Well-defined six-arm poly(ε-caprolactone-b-l-lactide, 6s-PCL-b-PLA) block copolymers were obtained with a range of segment molecular weights. However, in the case of six-arm poly(l-lactide-b-ε-caprolactone, 6s-PLA-b-PCL), disruption of the block structure was observed on account of competing transesterification reactions accompanying a chain-growth reaction. Such sequence-controlled block copolymers showed interesting phase morphologies, as evidenced by differential scanning calorimetry (DSC) studies. 6s-PCL-b-PLA showed two glass-transition temperatures and two melting temperatures characteristic of the amorphous and crystalline blocks. 6s-PCL-b-PLA and 6s-PLA-b-PCL with different segment chain lengths were solution blended (10 wt %) with a commercially sourced PLA. All the blends were highly transparent. The structure and properties of the blend were examined by DSC, measurement of mechanical properties, and scanning electron microscopy. The results show that a phase-separated 6s-PCL-b-PLA copolymer results in two- to three-fold improvement in tensile toughness without the loss of modulus. A possible hypothesis for the mechanism of tensile toughness in the blend has been proposed.

Recent developments in biodegradable block copolymers

AbstractBlock copolymers consist of two or more segments of polymer chains in a typical arrangement through connected covalent bonds. Biodegradable block copolymers have emerged as useful carriers for controlled drug release, tissue engineering, and other biomedical applications due to their ability to form colloidal systems and tunable properties. This review focuses on recent advancements in the synthesis, characterization, and biomedical applications of biodegradable block copolymers.

A rapid quantitation of cell attachment and spreading based on digital image analysis: Application for cell affinity and compatibility assessment of synthetic polymers

Accurate and rapid quantitation of cell attachment, spreading, and growth on a polymer thin film coated glass cover slide was developed by analyzing the digital images of cells stained with dyes. A biodegradable block copolymer poly(ethylene glycol)-block-poly(l-lactide-co-2-methyl-2-carboxyl-propylene carbonate) [PEG-b-P(LA-co-MCC)] was synthesized as model polymer with poly(L-lactic acid) [PLLA] as a control polymer. Only a small quantity of polymer (~5 mg) was needed in this method through dissolving in a solvent and casting on cover slides which were previously modified with dimethyl dichlorosilane (DMDC). Then it was seeded with cells and taken pictures with a digital camera under an optical microscope and analyzed with ImageJ software. Cell number and a series of morphological data were obtained, including cell area, circularity, perimeter and Feret's diameter, etc. The quantitative analysis results indicated that cells preferred to attach and spread on the surface of the copolymer PEG-b-P(LA-co-MCC) compared to PLLA during 24 h of cell culture. This efficient procedure provides a series of convincing statistical data to evaluate the direct interaction between cells and polymers with only an optical microscope, a digital camera and ImageJ software. It's a rapid, economic way for assessing cell affinity and compatibility of novel synthetic polymers by cell culture in vitro.

Self-Assembled PEGylated Amphiphilic Polypeptides for Gene Transfection

In the present study, three biodegradable block copolymers composed of a poly(ethylene glycole) block and a copolypeptide block with varying compositions of cationic L-lysine (L-Lys) and hydrophobic benzyl-L-glutamate (Bzl- L-Glu) were designed for gene delivery applications. The polypeptides were synthesized by ring opening polymerization (ROP) and after orthogonal deprotection of Boc-L-Lys side chains, the polymer exhibited an amphiphilic character. To bind or encapsulate plasmid DNA (pDNA), various formulations were investigated: Nanoprecipitation and emulsion technique using various organic solvents as well as an aqueous pH-controlled formulation method. The complex and nanoparticle (NP) formations were monitored by dynamic light scattering (DLS), and pDNA interaction was shown by gel electrophoresis and subsequent controlled release with heparin. The polypeptides were further tested for their cytotoxicity as well as biodegradability. The complexes and NPs presenting the most promising size distributions and DNA binding ability were subsequently evaluated for their transfection efficiency in HEK293T cells. The highest transfection efficiencies were obtained with an aqueous formulation of the polypeptide containing the highest L-Lys content and lowest proportion of hydrophobic, helical structures (P1* ), which is therefore a promising candidate for efficient gene delivery by biodegradable gene delivery vectors.

Design and Development of D‒α‒Tocopheryl Polyethylene Glycol Succinate‒block‒Poly(ε-Caprolactone) (TPGS-b-PCL) Nanocarriers for Solubilization and Controlled Release of Paclitaxel.

The objective of this study was to synthesize and characterize a set of biodegradable block copolymers based on TPGS-block-poly(ε-caprolactone) (TPGS-b-PCL) and to assess their self-assembled structures as a nanodelivery system for paclitaxel (PAX). The conjugation of PCL to TPGS was hypothesized to increase the stability and the drug solubilization characteristics of TPGS micelles. TPGS-b-PCL copolymer with various PCL/TPGS ratios were synthesized via ring opening bulk polymerization of ε-caprolactone using TPGS, with different molecular weights of PEG (1–5 kDa), as initiators and stannous octoate as a catalyst. The synthesized copolymers were characterized using 1H NMR, GPC, FTIR, XRD, and DSC. Assembly of block copolymers was achieved via the cosolvent evaporation method. The self-assembled structures were characterized for their size, polydispersity, and CMC using dynamic light scattering (DLS) technique. The results from the spectroscopic and thermal analyses confirmed the successful synthesis of the copolymers. Only copolymers that consisted of TPGS with PEG molecular weights ≥ 2000 Da were able to self-assemble and form nanocarriers of ≤200 nm in diameter. Moreover, TPGS2000-b-PCL4000, TPGS3500-b-PCL7000, and TPGS5000-b-PCL15000 micelles enhanced the aqueous solubility of PAX from 0.3 µg/mL up to 88.4 ug/mL in TPGS5000-b-PCL15000. Of the abovementioned micellar formulations, TPGS5000-b-PCL15000 showed the slowest in vitro release of PAX. Specifically, the PAX-loaded TPGS5000-b-PCL15000 micellar formulation showed less than 10% drug release within the first 12 h, and around 36% cumulative drug release within 72 h compared to 61% and 100% PAX release, respectively, from the commercially available formulation (Ebetaxel®) at the same time points. Our results point to a great potential for TPGS-b-PCL micelles to efficiently solubilize and control the release of PAX.

Minocycline hydrochloride loaded mPEG-PCLA membranes: Preparation and in vitro evaluation for periodontitis therapy

This study was aimed at alleviating shortcomings in the treatment of periodontitis by preparation of a biopolymer membrane loaded with minocycline hydrochloride (MH) inserted into periodontal pockets to treat infections. Monomethoxy-poly (ethylene glycol)-poly (ε-caprolactone-co-L-lactide) (mPEG-PCLA) is a biocompatible and biodegradable amphiphilic block copolymer. It, therefore, has attracted considerable attention in drug delivery systems and periodontal treatment. We chose it as a membrane material for MH-drug loading. The MH-loaded membranes were prepared by the solvent casting technique with the content of 5, 8 and 10 wt.%, respectively. Fourier transform infrared spectra (FTIR) revealed no interaction between MH and polymer. The drug-loaded membrane surface morphology was investigated by scanning electron microscopy (SEM). In vitro release studies showed that the initial drug release exceeded 40% within 24 h, followed by a sustained release for up to 2 weeks, which would enable the therapeutic level to maintain over a longer time. The antibacterial activity studies in vitro demonstrated a positive effect on the periodontal pathogen. MH drug-loaded membranes have no adverse effect on the growth of periodontal ligament fibroblasts in the MTT test. The study suggests that mPEG-PCLA membranes containing MH are a potential antibacterial drug delivery system for local treatment of periodontitis.

Photoactivated nanomotors via aggregation induced emission for enhanced phototherapy

Aggregation-induced emission (AIE) has, since its discovery, become a valuable tool in the field of nanoscience. AIEgenic molecules, which display highly stable fluorescence in an assembled state, have applications in various biomedical fields—including photodynamic therapy. Engineering structure-inherent, AIEgenic nanomaterials with motile properties is, however, still an unexplored frontier in the evolution of this potent technology. Here, we present phototactic/phototherapeutic nanomotors where biodegradable block copolymers decorated with AIE motifs can transduce radiant energy into motion and enhance thermophoretic motility driven by an asymmetric Au nanoshell. The hybrid nanomotors can harness two photon near-infrared radiation, triggering autonomous propulsion and simultaneous phototherapeutic generation of reactive oxygen species. The potential of these nanomotors to be applied in photodynamic therapy is demonstrated in vitro, where near-infrared light directed motion and reactive oxygen species induction synergistically enhance efficacy with a high level of spatial control.

Thermo-Rheological and Shape Memory Properties of Block and Random Copolymers of Lactide and ε-Caprolactone.

Biodegradable block and random copolymers have attracted numerous research interests in different areas, due to their capability to provide a broad range of properties. In this paper, an efficient strategy has been reported for preparing biodegradable PCL-PLA copolymers with improved thermal, mechanical and rheological properties. Two block-copolymers are synthesized by sequential addition of the cyclic esters lactide (L-LA or D,L-LA) and ε-caprolactone (CL) in presence of a dimethyl(salicylaldiminato)aluminium compound. The random copolymer of L-LA and CL was synthetized by using the same catalyst. Chain structure, molar mass, thermal, rheological and mechanical properties are characterized by NMR, SEC, TGA, DSC, Rheometry and DMTA. Experimental results show that by changing the stereochemistry and monomer distribution of the copolymers it is possible to obtain a variety of properties. Promising shape-memory properties are also observed in the di-block copolymers characterized by the co-crystallization of CL and L-LA segments. These materials show great potential to substitute oil-based polymers for packaging, electronics, and medicine applications.

Self-assembled PEGylated amphiphilic polypeptides for gene transfection.

In the present study, three biodegradable block copolymers composed of a poly(ethylene glycol) block and a copolypeptide block with varying compositions of cationic L-lysine (L-Lys) and hydrophobic benzyl-L-glutamate (Bzl-L-Glu) were designed for gene delivery applications. The polypeptides were synthesized by ring opening polymerization (ROP) and after orthogonal deprotection of Boc-L-Lys side chains, the polymer exhibited an amphiphilic character. To bind or encapsulate plasmid DNA (pDNA), different formulations were investigated: a nanoprecipitation and an emulsion technique using various organic solvents as well as an aqueous pH-controlled formulation method. The complex and nanoparticle (NP) formations were monitored by dynamic light scattering (DLS), and pDNA interaction was shown by gel electrophoresis and subsequent controlled release with heparin. The polypeptides were further tested for their cytotoxicity as well as biodegradability. The complexes and NPs presenting the most promising size distributions and pDNA binding ability were subsequently evaluated for their transfection efficiency in HEK293T cells. The highest transfection efficiencies were obtained with an aqueous formulation of the polypeptide containing the highest L-Lys content and lowest proportion of hydrophobic, helical structures (P1*), which is therefore a promising candidate for efficient gene delivery by biodegradable gene delivery vectors.