Biodegradable Drug Delivery System Research Articles

Application of ultrasound-assisted compression and 3D-printing semi-solid extrusion techniques to the development of sustained-release drug delivery systems based on a novel biodegradable aliphatic copolyester

The purpose of this study was to investigate the ability of two advanced hot-processing technologies, Ultrasound-Assisted Compression (USAC) and 3D-printing Semi-solid Extrusion (SSE), to manufacture sustained-release drug delivery systems based on a novel biodegradable aliphatic copolyester. The copolymer was synthesized from ω-pentadecalactone (PDL), 1,4-cyclohexanedimethanol (CHDM) and dimethyl succinate (DMS) (monomer ratio PDL/CHDM/DMS 70/30/30) by enzymatic ring opening polymerization and two-step melt polycondensation processes and has a random microstructure, a high molecular weight (107,100 g mol−1) and a relatively low melting point (∼65 °C). The antibacterial agent metronidazole (MTZ) was chosen as model drug and binary physical mixtures copolymer:drug were prepared at 90:10 and 70:30 w/w ratios. Thermal analysis studies evidenced that the formulations could be processed below their degradation temperatures. Drug delivery devices with dense and meshed structures were manufactured using USAC and SSE techniques, respectively, with USAC devices exhibiting more reproducible physical properties than the SSE systems. Powder X-ray diffraction and scanning electron microscopy studies showed a partial sintering of the copolyester during USAC processing while MTZ remained mostly crystalline. In contrast, the copolymer melted and the drug underwent some amorphization when processed using SSE. In vitro drug release studies in phosphate buffer (pH 6.8) showed that, after an initial burst release of metronidazole, USAC and SSE devices exhibited a prolonged and/or sustained drug release over 20 days. The initial burst release was dependent on the manufacturing technique and the drug/polymer ratio, being minimized for SSE devices containing 10 wt% MTZ. The whole drug release profiles fitted well to the Peppas-Sahlin model, being drug diffusion the predominant release mechanism. After the burst release, the sustained release period of USAC and SSE devices containing 10 wt% MTZ showed a good fit to the zero-order kinetic model, with faster drug release from the SSE devices due to the larger surface area of their meshed structure. In conclusion, this work demonstrates that processing the aliphatic copolyester by both USAC and SSE technologies provides an attractive strategy to manufacture biodegradable drug delivery systems for long-term release of metronidazole.

Hydrogel-Based Therapy for Age-Related Macular Degeneration: Current Innovations, Impediments, and Future Perspectives.

Age-related macular degeneration (AMD) is an ocular disease that leads to progressive photoreceptor death and visual impairment. Currently, the most common therapeutic strategy is to deliver anti-vascular endothelial growth factor (anti-VEGF) agents into the eyes of patients with wet AMD. However, this treatment method requires repeated injections, which potentially results in surgical complications and unwanted side effects for patients. An effective therapeutic approach for dry AMD also remains elusive. Therefore, there is a surge of enthusiasm for the developing the biodegradable drug delivery systems with sustained release capability and develop a promising therapeutic strategy. Notably, the strides made in hydrogels which possess intricate three-dimensional polymer networks have profoundly facilitated the treatments of AMD. Researchers have established diverse hydrogel-based delivery systems with marvelous biocompatibility and efficacy. Advantageously, these hydrogel-based transplantation therapies provide promising opportunities for vision restoration. Herein, we provide an overview of the properties and potential of hydrogels for ocular delivery. We introduce recent advances in the utilization of hydrogels for the delivery of anti-VEGF and in cell implantation. Further refinements of these findings would lay the basis for developing more rational and curative therapies for AMD.

Effect of Biodegradable Mifepristone Drug Delivery System on the Ultrastructure and Angiogenesis Related Factors of Adenomyosis Cells

The aim of this research aimed to analyze the effects of degradable mifepristone nano-drug delivery system (DDS) on the ultrastructure, proliferation, apoptosis, and angiogenesis of adenomyosis cells. Drug-loaded nanoparticles (DNPs) of poly lactic-co-glycolic acid (PLGA) were prepared. The particle size distribution and surface Zeta potential (SZP) of nanoparticles (NPs) were detected. The morphology of NPS was subjected to observation by transmission electron microscope (TEM). Adenomyosis lesion cells were cultured by tissue digestion method, and the cell morphology was observed and identified. The cells were divided into blank control (NC), mifepristone, and mifepristone/PLGA groups. The cell proliferation, ultrastructure, apoptosis, and the expression of Survivin, VEGFR1, and VEGFR2 were detected by MTT, TEM, flow cytometry (FC), and immuno-histochemistry, respectively. The results suggested that the average particle size of mifepristone/PLGA NPs was (185.6±12.9) nm, and the SZP was (−9.5±0.9) mV. It presented the characteristics of circularity, uniform distribution, and smooth surface under TEM. As against the raw drug mifepristone, the release time of mifepristone/PLGA NPs was prolonged, and the drug release rate reached 87.4% at 72 h. As against NC, the cell proliferation rate (CPR) was clearly decreased, the apoptosis rate (AR) was increased, and Survivin, VEGFR1, and VEGFR2 had a decrease in mifepristone and mifepristone/PLGA groups (P <0.05). As against mifepristone group, the CPR was clearly decreased, the AR was increased, and Survivin, VEGFR1, and VEGFR2 had a decrease in mifepristone/PLGA group (P <0.05). In conclusion, mifepristone PLGA DNPs were able to delay drug release. Mifepristone can inhibit angiogenesis and promote apoptosis of adenomyosis by affecting the expression of Survivin, VEGFR1, and VEGFR2, thus playing a role in the treatment of adenomyosis.

A functional tacrolimus-releasing nerve wrap for enhancing nerve regeneration following surgical nerve repair

JOURNAL/nrgr/04.03/01300535-202501000-00036/figure1/v/2024-05-10T114357Z/r/image-tiff Axonal regeneration following surgical nerve repair is slow and often incomplete, resulting in poor functional recovery which sometimes contributes to lifelong disability. Currently, there are no FDA-approved therapies available to promote nerve regeneration. Tacrolimus accelerates axonal regeneration, but systemic side effects presently outweigh its potential benefits for peripheral nerve surgery. The authors describe herein a biodegradable polyurethane-based drug delivery system for the sustained local release of tacrolimus at the nerve repair site, with suitable properties for scalable production and clinical application, aiming to promote nerve regeneration and functional recovery with minimal systemic drug exposure. Tacrolimus is encapsulated into co-axially electrospun polycarbonate-urethane nanofibers to generate an implantable nerve wrap that releases therapeutic doses of bioactive tacrolimus over 31 days. Size and drug loading are adjustable for applications in small and large caliber nerves, and the wrap degrades within 120 days into biocompatible byproducts. Tacrolimus released from the nerve wrap promotes axon elongation in vitro and accelerates nerve regeneration and functional recovery in preclinical nerve repair models while off-target systemic drug exposure is reduced by 80% compared with systemic delivery. Given its surgical suitability and preclinical efficacy and safety, this system may provide a readily translatable approach to support axonal regeneration and recovery in patients undergoing nerve surgery.

Investigating the Impact of Polyvinyl Alcohol Addition on the Thermal Behavior and Chemical Structure of Electrospun Cellulose Nanofibers

The study aimed to investigate the effect of adding polyvinyl alcohol (PVA) on the chemical and thermal properties of cellulose nanofibers (CNFs). The CNF was prepared using electrospinning with varying amounts of PVA, and the resulting samples were analyzed using Fourier-transform infrared (FTIR) spectroscopy and Thermogravimetric analysis (TGA). The FTIR results showed that adding PVA did not significantly affect the chemical structure of CNF but led to the appearance of new peaks attributed to the characteristic peaks of both CNF and PVA. Moreover, the TGA results revealed that all samples underwent weight degradation after being heated from 350°C. The addition and removal of PVA did not significantly alter the thermal behavior of the CNF. Overall, the results suggested that PVA can be used as a compatible additive to CNF without significant changes to their properties, which could have potential applications in various fields, including biodegradable packaging and drug delivery systems.

Lentinan-functionalized PBAE-G-nanodiamonds as an adjuvant to induce cGAS-STING pathway-mediated macrophage activation and immune enhancement

A series of biodegradable nanoparticle-based drug delivery systems have been designed utilizing poly(β-amino ester)-guanidine-phenylboronic acid (PBAE-G) polymers. In this study, a novel Lentinan-Functionalized PBAE-G-nanodiamond system was developed to carry ovalbumin (LNT-PBAE-G-ND@OVA). The impact of this drug delivery system on the activation and maturation of macrophages was then assessed. Furthermore, LNT-PBAE-G-ND@OVA induced potent antibody response and showed no obvious toxicity in vitro and in vivo. Moreover, treatment with LNT-PBAE-G-ND@OVA was sufficient to alter the expression of genes associated with the cGAS-STING pathway, and the LNT-PBAE-G-ND@OVA induced upregulation of costimulatory molecules. LNT-PBAE-G-ND@OVA treatment was sufficient to induce macrophage activation through a complex mechanism in which cGAS-STING signaling plays an integral role.

Exploiting Benefits of Vaterite Metastability to Design Degradable Systems for Biomedical Applications.

The widespread application of calcium carbonate is determined by its high availability in nature and simplicity of synthesis in laboratory conditions. Moreover, calcium carbonate possesses highly attractive physicochemical properties that make it suitable for a wide range of biomedical applications. This review provides a conclusive analysis of the results on using the tunable vaterite metastability in the development of biodegradable drug delivery systems and therapeutic vehicles with a controlled and sustained release of the incorporated cargo. This manuscript highlights the nuances of vaterite recrystallization to non-porous calcite, dissolution at acidic pH, biodegradation at in vivo conditions and control over these processes. This review outlines the main benefits of vaterite instability for the controlled liberation of the encapsulated molecules for the development of biodegradable natural and synthetic polymeric materials for biomedical purposes.

Biodegradable polyester-based nano drug delivery system in cancer chemotherapy: a review of recent progress (2021-2023).

Cancer presents a formidable threat to human health, with the majority of cases currently lacking a complete cure. Frequently, chemotherapy drugs are required to impede its progression. However, these drugs frequently suffer from drawbacks such as poor selectivity, limited water solubility, low bioavailability, and a propensity for causing organ toxicity. Consequently, a concerted effort has been made to seek improved drug delivery systems. Nano-drug delivery systems based on biodegradable polyesters have emerged as a subject of widespread interest in this pursuit. Extensive research has demonstrated their potential for offering high bioavailability, effective encapsulation, controlled release, and minimal toxicity. Notably, poly (ε-caprolactone) (PCL), poly (lactic-co-glycolic acid) (PLGA), and polylactic acid (PLA) have gained prominence as the most widely utilized options as carriers of the nano drug delivery system. This paper comprehensively reviews recent research on these materials as nano-carriers for delivering chemotherapeutic drugs, summarizing their latest advancements, acknowledging their limitations, and forecasting future research directions.

Evaluation of the properties of dry bacterial cellulose synthesized from coffee kombucha fermentation dried with different drying methods

The fermentation of coffee kombucha (CK) utilizes carbohydrate substrates to produce bacterial cellulose (BC), a naturally occurring material synthesized by some bacteria including Gluconacetobacter spp. BC can be used to develop materials for biomedical and food industry applications including biomaterial and biodegradable packaging materials, medical devices, biosensors, or drug delivery systems. BC contains approximately 97% water, which is not convenient and portable for many applications. Drying increases the stability of BC and may influence the properties of BC. The effect of drying methods on the BC properties can determine the suitability of the material for various applications. The objectives of this study were to use four drying methods to synthesize BCs from the fermentation of CK and evaluate their physicochemical, mechanical, and morphological properties. The drying methods included: oven-drying (OD), freeze-drying, vacuum-oven-drying, and Büchner funnel vacuum-drying (BFVD). FTIR analyses confirmed the structure of cellulose for all methods. OD-BCs had the highest tensile stress at break with 24.67 ± 4.40 (MPa). SEM images showed randomly structured fibers with diameters ranging from 61.58 to 72.18 nm. XRD analysis revealed that OD had the highest degree of crystallinity with 78.67%. All BCs decomposed between 230 and 400 °C. This study demonstrated that using different drying methods could alter the structural properties of BCs potentially providing distinctive applications in various industries.

Complexation between chitosan and carboxymethyl cellulose in weakly acidic, neutral, and weakly alcaline media

The interaction between carboxymethyl cellulose and partially reacetylated chitosan soluble in acidic and alkaline aqueous media is studied by light scattering and isothermal titration calorimetry in a wide pH range. It is shown that the formation of polyelectrolyte complexes (PEC) can occur in the pH range of 6–8, while this pair of polyelectrolytes loses the ability to complexation upon transition to a more alkaline medium. The revealed dependence of the observed enthalpy of interaction on the ionization enthalpy of the buffer indicates the participation of proton transfer from the buffer substance to chitosan and its additional ionization in the binding process. This phenomenon is first observed in a mixture of a weak polybase chitosan and a weak polyacid. The possibility to obtain soluble nonstoichiometric PEC by a direct mixing of the components in a weakly alkaline medium is shown. The resulting PECs are polymolecular particles in shape close to homogeneous spheres with a radius of about 100 nm. The obtained results are promising for creating of biocompatible and biodegradable drug delivery systems.

Synthesis and Characterization of Curcumin Incorporated Multi Component Nano-Scaffold with Enhanced Anti-bacterial and Wound Healing Properties.

Wound healing is one of the major challenges in chronic diseases; the current treatment options are less effective with undesirable side effects and are expensive. Extensive research is carried out to develop cost-effective, natural, biodegradable wound dressings that can reduce oxidative stress and inflammation and prevent bacterial infections. Curcumin has a plethora of therapeutic applications; however, its low solubility limits its clinical use. In this study, curcumin nanoparticles (Cur NP) and curcumin-chitosan nanoparticles (CCNP) were incorporated into the chitosan collagen vanillin scaffold, characterized, and investigated their potential wound healing properties. The nano-scaffolds were prepared by freeze-drying method and were characterized using Fourier transform infrared spectroscopy, X-ray diffraction, nanoparticle tracking analysis, and scanning electron microscopy. The drug release, antioxidant, antibacterial, and wound healing properties were assessed by in vitro assays. Cur nano-scaffolds showed particle sizes of 195.9 nm and 110.6 nm for Cur NP+VC and CCNP+VC, respectively. The curcumin encapsulated in the Cur NP+VC and CC+VC nano-scaffolds showed a release profile of > 60% and an improved antioxidant activity of greater than 80%. The nanoscaffolds were antagonistic against Escherichia coli and Staphylococcus aureus and enhanced wound healing capacity of 85.62 % and 77.05% in the murine cell line. The curcumin nano-scaffold is a biodegradable and effective drug delivery system for topical use that can act as an antioxidant, facilitate wound healing, as well as prevent bacterial infections.

Biodegradable Microspheres and Hydrogel Drug Delivery System of Tumor Necrosis Factor (TNF) Inhibitor and Growth Differentiation Factor 5 (GDF5) Reduces Disk Inflammation in the Rabbit Model.

Preclinical study. Develop and test a drug delivery system (DDS) composed of anti-inflammatories and growth factors in the rabbit disk injury model. Biological therapies that inhibit inflammation or enhance cell proliferation can alter intervertebral disk (IVD) homeostasis to favor regeneration. As biological molecules have short half-lives and one molecule may not cover multiple disease pathways, effective treatments may require a combination of growth factors and anti-inflammatory agents delivered in a sustained manner. Biodegradable microspheres were generated separately to encapsulate tumor necrosis factor alpha (TNFα) inhibitors [etanercept (ETN)] or growth differentiation factor 5 (GDF5) and were embedded into a thermoresponsive hydrogel. Release kinetics and activity of ETN and GDF5 were measured in vitro . For in vivo testing, New Zealand White rabbits (n=12) underwent surgery for disk puncture and treatment with blank-DDS, ETN-DDS, or ETN+GDF5-DDS at levels L34, L45, and L56. Radiographic and magnetic resonance images of the spines were obtained. The IVDs were isolated for histologic and gene expression analyses. ETN and GDF5 were encapsulated into poly (L-lactide-co-glycolide) microspheres and had average initial bursts of 2.4±0.1 and 11.2±0.7μg from DDS, respectively. In vitro studies confirmed that ETN-DDS inhibited TNFα-induced cytokine release and GDF5-DDS induced protein phosphorylation. In vivo studies showed that rabbit IVDs treated with ETN+GDF5-DDS had better histologic outcomes, higher levels of extracellular, and lower levels of inflammatory gene expression than IVDs treated with blank-DDS or ETN-DDS. This pilot study demonstrated that DDS can be fabricated to deliver sustained and therapeutic dosages of ETN and GDF5. In addition, ETN+GDF5-DDS may have greater anti-inflammatory and regenerative effects than ETN-DDS alone. Thus, intradiscal injection of controlled release TNF-α inhibitors and growth factors may be a promising treatment to reduce disk inflammation and back pain.

Abstract 2703: Evaluation of the effect of tumor-targeted and immunomodulating nanoparticles on the activity of cytotoxic T cells using CAR T cells as an in vitro model

Abstract In solid tumors, there are multiple barriers that prevent anticancer agents and T cells from being able to be delivered into and reach tumor cells. For effective antitumor activity, it is necessary to have direct interactions between cytotoxic T cells and tumor cells. Hyaluronic acid and Iron oxide both have distinctive properties that are advantageous for the development of biocompatible and biodegradable nanoparticle drug delivery systems for cancer. We have developed several targeting and immunomodulatory ligands that can be conjugated to the nanoparticles while carrying chemotherapy or molecular targeted agents for targeted cancer therapy as shown in Table 1. Although the therapeutic efficacy of those targeted nanoparticles has been demonstrated in mouse tumor models, the effect of nanoparticles and their payload drugs on the activities of tumor specific cytotoxic T cells is still unclear. To determine the effect of those nanoparticles on T cell immune responses, CAR T cells provided a well-suited in vitro cellular model. In this study, anti-mesothelin CAR T cells generated from lentiviral CAR T vector transduced T cells were incubated with nanoparticle/drugs and free drugs. The effect of various nanoparticles on CAR T cell viability, and in vitro cytotoxicity on pancreatic cancer cells was evaluated by live/dead, Alamarblue and SRB proliferation Assays. Our results showed that the incubation of CAR T cells with targeted nanoparticles/drugs did not reduce CAR T cells' viability and did not inhibit T cells' activity in killing tumor cells. The ATFmmp14-HANP/SN38 nanoparticle showed an enhanced effect of CAR T cells. Thus, this nanoparticle/drug has the potential for the development of combination therapy with CAR T cells to improve the CAR T cell delivery while synergizing anti-tumor effect by targeted drug delivery, stroma modulation, and tumor cell killing by drug and CAR T cells. Table 1. Nanoparticle formulations overview Nanoparticle Types Target Payload Mechanism of action Observed Results (in vivo) Observed Results (in vitro) ATFmmp14-HANP/SN38:ATFmmp14 conjugated HANP uPAR CD44 SN38 (an active metabolite of irinotecan) Inhibits DNA topoiso-merase I, causing DNA single strand breaks and DNA damage. Significant tumor growth inhibition in human pancreatic and breast cancer PDX models. HANP more effective towards pancreatic cell line and less toxic against CAR T cells: Greater anti-tumor with combination HANP/GKT831: HANP CD44 Setanaxib (GKT831:an inhibitor of NOX1 and NOX4 Reduce the level of reactive oxygen species (ROS): DNA repair downregulation, increases DNA damage Efficient delivery into mouse breast PDX tumors and sensitizing tumor cells to radiotherapy and DNA damaging agents. Nontoxic towards CAR T cells: limited additional therapeutic effects PDY1-HANP/Avasimibe: PD-L1 blocking PDY1 peptide conjugated HANP PD-L1 CD44 Avasimibe (Ava), an inhibitor of acyl-Coenzyme A:cholesterolacyltransferase Decreases intracellular cholesterol.Inhibit tumor cell growth, Activate cytotoxic T cells Efficient delivery into mouse colon tumors, Inhibition of tumor growth: Increased levels of CD8+ T cells and CD68+ Macrophages in tumors Nontoxic towards pancreatic cell lines and CAR T cells: limited additional therapeutic effects ATFmmp14-IONP-DOX: ATFmmp14 conjugated IONP uPAR Doxorubicin Direct DNA damage and inhibits DNA repair by inhibiting topoisomerase Significantly inhibited tumor growth in human pancreatic and breast cancer PDX model ATFmmp14-IONP/DOX more effective towards pancreatic cancer cell lines and less toxic against CAR T cells: slightly increased killing of tumor cells with combination ATFmmp14: Amino terminal fragment (ATF) of uPA fused with MMP14 catalytic domain; PD1Y: PD1 peptide mimetic that binds to and inhibit PD-L1 HANP: Hyaluronic acid nanoparticle; IONP: Iron oxide nanoparticle Citation Format: Kory Wells, Tongrui Lui, Lei Zhu, Chrystal Paulos, Lily Yang. Evaluation of the effect of tumor-targeted and immunomodulating nanoparticles on the activity of cytotoxic T cells using CAR T cells as an in vitro model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2703.

Disulfide-Bridged Dendritic Organosilicas-Based Biodegradable Molecularly Imprinted Polymers for Multiple Targeting and pH/Redox-Responsive Drug Release toward Chemical/Photodynamic Synergistic Tumor Therapy.

In this study, a sialic acid (SA) and transferrin (TF) imprinted biodegradable disulfide bridging organosilicas-based drug delivery system (SS-DMONS/DOX-Ce6@MIPs) for targeted cancer therapy is constructed, for the first time. Disulfide bridged dendritic mesoporous organosilicas nanoparticles (SS-DMONs) not only enhance drug loading as the drug repository, but also provide enough specific surface area for the molecular imprinting shell to expose more degradation and imprinted sites on the surface. In addition, SS can be disturbed in a highly reducing tumor microenvironment to achieve degradation. The biodegradable imprinting film, prepared with customized 2-amino-N-(3,4-dihydroxyphenethyl)-3-mercaptopropanamide and 4-mercaptophenylboronic acid as functional monomers, endows SS-DMONs with active targeting capacity, and responsive drug release through degradation under acidic and highly reductive tumor microenvironment. SS-DMONS/DOX-Ce6@MIPs after binding of TF can target tumor cells actively through multiple interactions, including the affinity between antigen and antibody, and the specific recognition between molecularly imprinted polymers and template molecules. Under laser irradiation the loaded chlorin e6 (Ce6) that can produce toxic reactive oxygen, combined with the doxorubicin (DOX), achieves chemical/photodynamic synergistic anticancer effects. SS-DMONS/DOX-Ce6@MIPs present excellent tumor targeting and dual-responsive drug release, which provides an effective strategy for chemical/photodynamic antitumor therapy.

Nanofibers: The Novel Technology

Abstract: Polymer nanofibers, with diameters in the nanometer range, possess larger surface areas per unit mass and permit easier addition of surface functionalities compared with polymer microfibers. Research on polymer nanofibers, nanofiber mats, and their applications has seen a remarkable growth over the last few years. Unique properties of Nanofibers have attracted for the designing of controlled drug delivery systems due to high surface area to volume ratio, porosity so only we can applied in advance application such as Biodegradable and controlled drug delivery systems. The benefits of the fibrous carriers are site specific delivery of drugs to the body.

Overcoming Treatment Challenges in Posterior Segment Diseases with Biodegradable Nano-Based Drug Delivery Systems.

Posterior segment eye diseases present a challenge in treatment due to the complex structures in the eye that serve as robust static and dynamic barriers, limiting the penetration, residence time, and bioavailability of topical and intraocular medications. This hinders effective treatment and requires frequent dosing, such as the regular use of eye drops or visits to the ophthalmologist for intravitreal injections, to manage the disease. Moreover, the drugs must be biodegradable to minimize toxicity and adverse reactions, as well as small enough to not affect the visual axis. The development of biodegradable nano-based drug delivery systems (DDSs) can be the solution to these challenges. First, they can stay in ocular tissues for longer periods of time, reducing the frequency of drug administration. Second, they can pass through ocular barriers, offering higher bioavailability to targeted tissues that are otherwise inaccessible. Third, they can be made up of polymers that are biodegradable and nanosized. Hence, therapeutic innovations in biodegradable nanosized DDS have been widely explored for ophthalmic drug delivery applications. In this review, we will present a concise overview of DDSs utilized in the treatment of ocular diseases. We will then examine the current therapeutic challenges faced in the management of posterior segment diseases and explore how various types of biodegradable nanocarriers can enhance our therapeutic arsenal. A literature review of the pre-clinical and clinical studies published between 2017 and 2023 was conducted. Through the advances in biodegradable materials, combined with a better understanding of ocular pharmacology, the nano-based DDSs have rapidly evolved, showing great promise to overcome challenges currently encountered by clinicians.

Updates on Biodegradable Formulations for Ocular Drug Delivery.

The complex nature of the ocular drug delivery barrier presents a significant challenge to the effective administration of drugs, resulting in poor therapeutic outcomes. To address this issue, it is essential to investigate new drugs and alternative delivery routes and vehicles. One promising approach is the use of biodegradable formulations to develop potential ocular drug delivery technologies. These include hydrogels, biodegradable microneedles, implants, and polymeric nanocarriers such as liposomes, nanoparticles, nanosuspensions, nanomicelles, and nanoemulsions. The research in these areas is rapidly growing. In this review, we provide an overview of recent updates in biodegradable formulations for ocular drug delivery over the past decade. Additionally, we examine the clinical use of different biodegradable formulations in various ocular diseases. The aim of this review is to gain a deeper understanding of potential future trends in biodegradable ocular drug delivery systems and to raise awareness of their potential for practical clinical application as a means of providing new treatment options for ocular diseases.

The Advancement of Biodegradable Polyesters as Delivery Systems for Camptothecin and Its Analogues-A Status Report.

Camptothecin (CPT) has demonstrated antitumor activity in lung, ovarian, breast, pancreas, and stomach cancers. However, this drug, like many other potent anticancer agents, is extremely water-insoluble. Furthermore, pharmacology studies have revealed that prolonged schedules must be administered continuously. For these reasons, several of its water-soluble analogues, prodrugs, and macromolecular conjugates have been synthesized, and various formulation approaches have been investigated. Biodegradable polyesters have gained popularity in cancer treatment in recent years. A number of biodegradable polymeric drug delivery systems (DDSs), designed for localized and systemic administration of therapeutic agents, as well as tumor-targeting macromolecules, have entered clinical trials, demonstrating the importance of biodegradable polyesters in cancer therapy. Biodegradable polyester-based DDSs have the potential to deliver the payload to the target while also increasing drug availability at intended site. The systemic toxicity and serious side-effects associated with conventional cancer therapies can be significantly reduced with targeted polymeric systems. This review elaborates on the use of biodegradable polyesters in the delivery of CPT and its analogues. The design of various DDSs based on biodegradable polyesters has been described, with the drug either adsorbed on the polymer's surface or encapsulated within its macrostructure, as well as those in which a hydrolyzed chemical bond is formed between the active substance and the polymer chain. The data related to the type of DDSs, the kind of linkage, and the details of in vitro and in vivo studies are included.

Biodegradable porous polymeric drug as a drug delivery system: alleviation of doxorubicin-induced cardiotoxicity via passive targeted release.

Doxorubicin (DOX) is an effective chemotherapeutic drug developed against a broad range of cancers, and its clinical applications are greatly restricted by the side effects of severe cardiotoxicity during tumour treatment. Herein, the DOX-loaded biodegradable porous polymeric drug, namely, Fc-Ma-DOX, which was stable in the circulation, but easy to compose in the acidic medium, was used as the drug delivery system avoiding the indiscriminate release of DOX. Fc-Ma was constructed via the copolymerization of 1,1'-ferrocenecarbaldehyde with d-mannitol (Ma) through the pH-sensitive acetal bonds. Echocardiography, biochemical parameters, pathological examination, and western blot results showed that DOX treatment caused increased myocardial injury and oxidative stress damage. In contrast, treatment with Fc-Ma-DOX significantly reduced myocardial injury and oxidative stress by DOX treatment. Notably, in the Fc-Ma-DOX treatment group, we observed a significant decrease in the uptake of DOX by H9C2 cells and a significant decrease in reactive oxygen species (ROS) production.

Application of Degradable Polymers for the Treatment of Wounds and Tumors

Degradable polymers are of great significance in bacteriostatic and cancer treatment. Biodegradable biomaterials have the characteristics of high safety, good environmental protection and good therapeutic effect. This article mainly introduces the application of the polymerization strategy in the biomedical field. In the direction of bacteriostasis, degradable polymers provide a series of new and effective ideas for researchers. For example, the biodegradable antimicrobial gene vector based on tobramycin, a kind of antibiotic, coupled with polyaspartic acid (TPT) effectively realized the antimicrobial treatment and restoration of skin damage. A multifunctional injectable hydrogel dressing that integrates electrical conductivity, good antioxidant capacity and antibacterial properties has been designed to treat skin injuries. Supramolecular polymers with strong antibacterial effect and controllable degradability were used to prepare biodegradable antibiotics to enhance the antibacterial effect of antibiotics against drug-resistant bacteria. In addition, degradable polymers also show great potential in the treatment of cancer. For example, scientists have discovered that drug release can be triggered from tumor-targeted polymer nanoparticles through the process of polymer degradation mediated by reactive oxygen species. The development of a rapidly degraded chitosan based multilayer controlled release membrane provides a theoretical basis for the preparation of customized multilayer membranes for drug administration. The adoption of the concept of the macromolecular engineering, which mixes drugs with polymers, opens up a new way to design polymer biodegradable drug delivery systems. Thus, the potential of biodegradable polymers in various interdisciplinary fields has been highly valued, and they will be more widely used in production and life in the future.