Nanosponges: As a Dynamic Drug Delivery Approach for Targeted Delivery

Recent advancements in nanotechnology have resulted in improved medicine delivery to the target site. Nanosponges are three-dimensional drug delivery systems that are nanoscale in size and created by cross-linking polymers. The introduction of Nanosponges has been a significant step toward overcoming issues such as drug toxicity, low bioavailability, and predictable medication release. Using a new way of nanotechnology, nanosponges, which are porous with small sponges (below one microm) flowing throughout the body, have demonstrated excellent results in delivering drugs. As a result, they reach the target place, attach to the skin's surface, and slowly release the medicine. Nanosponges can be used to encapsulate a wide range of medicines, including both hydrophilic and lipophilic pharmaceuticals. The medication delivery method using nanosponges is one of the most promising fields in pharmacy. It can be used as a biocatalyst carrier for vaccines, antibodies, enzymes, and proteins to be released. The existing study enlightens on the preparation method, evaluation, and prospective application in a medication delivery system and also focuses on patents filed in the field of nanosponges.Copyright © 2023 The Authors.

An industry update: the latest developments in therapeutic delivery covering May 2020.

The present industry update covers the period 1-31 May 2020, with information sourced from company press releases, regulatory and patent agencies as well as scientific literature.

Recent advancements in single dose slow-release devices for prophylactic vaccines.

Single dose slow-release vaccines herald a new era in vaccine administration. An ideal device for slow-release vaccine delivery would be minimally invasive and self-administered, making these approaches an attractive alternative for mass vaccination programs, particularly during the time of a pandemic. In this review article, we discuss the latest advances in this field, specifically for prophylactic vaccines able to prevent infectious diseases. Recent studies have found that slow-release vaccines elicit better immune responses and often do not require cold chain transportation and storage, thus drastically reducing the cost, streamlining distribution, and improving efficacy. This promise has attracted significant attention, especially when poor patient compliance of the standard multidose vaccine regimes is considered. Single dose slow-release vaccines are the next generation of vaccine tools that could overcome most of the shortcomings of present vaccination programs and be the next platform technology to combat future pandemics. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Implantable Materials and Surgical Technologies > Nanomaterials and Implants Biology-Inspired Nanomaterials > Protein and Virus-Based Structures.

Controlled release nanomedicine (CRNM) of aspirin using "biomimetic niosomal nanoparticles (BNNs)”for Covid-19 and cardiovascular treatment: DOE based optimization

Biomimetic strategies can be adopted to improve biopharmaceutical aspects. Subsequently, Biomimetic reconstitutable pegylated amphiphilic lipid nanocarriers have high translational potential for systemic controlled drug delivery;however, such an improvised system for systemic aspirin delivery exploring nanotechnology is not available. Systemic administration of aspirin and its controlled delivery can significantly control blood clotting events, leading to stroke, which has immediate applications in cardiovascular diseases and Covid-19. In this work, we are developing aspirin sustained release pegylated amphiphilic self-assembling nanoparticles to develop reconstitutable aspirin injections by solvent-based co-precipitation method with phase inversion technique that leads to novel "biomimetic niosomal nanoparticles (BNNs).” DOE led optimization is done to develop Design of space for optimized particles. Upon reconstitution of solid powder, the particle size was 144.8 ± 12.90 nm with a surface charge of -29.2 ± 2.24 mV. The entrapment efficiency was found to be 49 ± 0.15%, wherein 96.99 ± 1.57% of the drug was released in 24hr showing super case II transport-based drug release mechanism. The formulation has the least hemolysis while showing significant suppression of platelet aggregation. MTT assay does not show any significant cytotoxicity. This is a potential nanoparticle that can be explored for developing aspirin injection, which is not available.

Stimuli-responsive hydrogels for cancer immunotherapy

Immunotherapy plays an important role in cancer treatment by activating or suppressing the immune system. However, there are still a series of challenges to overcome regarding the delivery vehicles of immunotherapeutic agents and their effective activation at tumor sites. Meanwhile, owing to their well-hydrated environment and capability of immobilizing biological cargos, hydrogels in combination with immunotherapies provide a chance to enhance the antitumor immune response with reduced side effects. In addition, stimuli-responsiveness has been also widely applied to optimize the pharmacokinetics with an improved therapeutic outcome. In this review, we discuss the opportunities for the combination of immunotherapy and stimuli-responsive hydrogels, such as light, temperature, ultrasound and magnetically responsive hydrogels, for effective cancer treatment. Finally, we explore the potential of stimuli-responsive hydrogels as vaccine implants against cancer and Covid-19.

A comprehensive review on the COVID-19 vaccine and drug delivery applications of interpenetrating polymer networks.

An interpenetrating polymer network (IPNs) is a concoction of two or more polymers (natural, synthetic, and/or a combination of both) in which at least one polymer is synthesized or crosslinked in the intimate presence of the other. These three-dimensional networked systems have gained prominence in a series of biomedical applications, especially in the last two decades. The last decades witnessed a surge in the meaningful applications of interpenetrating polymer networks, especially in drug delivery as simple IPN systems advanced and resulted in the formation of highly efficient microspheres, nanoparticles, nanogels, and hydrogels, intelligent enough to sense and respond to changes in external stimuli such as temperature, pH, and ionic strength. The structure of the polymers, crosslinking agents, crosslinking density, and polymerization method play an integral role in determining the properties and application of IPNs in drug delivery. This review article is a modest effort to highlight the importance and applications of different types of interpenetrating polymer networks for the sustained, site-specific drug delivery of various therapeutic formulations, as witnessed in scientific research literature over the past 22 years (2000-2022). A special section of the manuscript is devoted to studying the efficacy of network polymers in vaccine delivery and highlighting the future scope (if any) of incorporating the IPN system in COVID-related vaccine/drug delivery. Four key focus areas in this review article [1, 2].

Nanosponges: Advancement in Nanotherapeutics

The emergence of nanotechnology paves the way for improving disease therapy strategies. An investigation into the progression of the release of the medication targeting the specified predetermined location is a significant factor to consider. Due to the ability to advance existing products and to develop new products in a variety of applications, the nanotechnology industry is considered an evolving technology. Cyclodextrin-based porous nanoparticles or unique nano-sponges (NSs) which have recently been used in the pharmaceutical, biomedical, and cosmetic industries are the main elements of this growth. This superior technology can circumvent the defects of current techniques by its ability to attack and visualize tumour sites. A biodegradable and biocompatible feature along with a built-in high surface area resulting in enormous amounts of drug loading and biomimetic design, and the ability to control nanoparticles size are just a handful of good attractive attributes that find this technique as an overwhelming advantage in the field of nanomedicine. This review article is organized such that we first explored the unique features of these nanosponges and the diverse methods for synthesizing, followed by the drug loading and release principle and application based on drug delivery, targeting, boosting solubility of BCS Class II and IV drugs, others in biomedicine and more. Finally, the recent progress on the use of biomimetic nanosponge as a pandemic tool due to the SARS-CoV-2 virus briefly comes into line. Copyright © RJPT All right reserved.

Encapsulation of Bromelain in Combined Sodium Alginate and Amino Acid Carriers: Experimental Design of Simplex-Centroid Mixtures for Digestibility Evaluation.

Bromelain has potential as an analgesic, an anti-inflammatory, and in cancer treatments. Despite its therapeutic effects, this protein undergoes denaturation when administered orally. Microencapsulation processes have shown potential in protein protection and as controlled release systems. Thus, this paper aimed to develop encapsulating systems using sodium alginate as a carrier material and positively charged amino acids as stabilizing agents for the controlled release of bromelain in in vitro tests. The systems were produced from the experimental design of centroid simplex mixtures. Characterizations were performed by FTIR showing that bromelain was encapsulated in all systems. XRD analyses showed that the systems are semi-crystalline solids and through SEM analysis the morphology of the formed systems followed a pattern of rough microparticles. The application of statistical analysis showed that the systems presented behavior that can be evaluated by quadratic and special cubic models, with a p-value < 0.05. The interaction between amino acids and bromelain/alginate was evaluated, and free bromelain showed a reduction of 74.0% in protein content and 23.6% in enzymatic activity at the end of gastric digestion. Furthermore, a reduction of 91.6% of protein content and 65.9% of enzymatic activity was observed at the end of intestinal digestion. The Lis system showed better interaction due to the increased stability of bromelain in terms of the amount of proteins (above 63% until the end of the intestinal phase) and the enzymatic activity of 89.3%. Thus, this study proposes the development of pH-controlled release systems aiming at increasing the stability and bioavailability of bromelain in intestinal systems.

Microfluidic preparation of antimicrobial microparticles composed of l-lactide/1,3-dioxolane (co)polymers loaded with quercetin.

The resistance of microorganisms against commonly used antibiotics is becoming an increasingly important problem in the food and pharmaceutical industries. Therefore, the development of novel bactericidal agents, as well as the design of drug delivery systems based on materials composed of biocompatible and biodegradable building blocks, has attracted increasing attention. To address this challenge, microparticles composed of l-lactide homopolymer and l-lactide/1,3-dioxolane (co)polymers loaded with quercetin (Q) were fabricated by using a microfluidic technique. This method enables the preparation of homogeneous particles with sizes ranging from 60 to 80 µm, composed of degradable semicrystalline or amorphous (co)polyesters. The microencapsulation of Q in a (co)polymeric matrix enables prolonged release of the antimicrobial agent. The antibacterial properties of the obtained biocompatible microparticles are confirmed by the agar diffusion plate method for various bacterial strains. Therefore, Q-loaded microparticles can have important applications in food preservation as a novel antimicrobial system.

Advances in delivery methods of Arthrospira platensis (spirulina) for enhanced therapeutic outcomes.

Arthrospira platensis (A. platensis) aqueous extract has massive amounts of natural products that can be used as future drugs, such as C-phycocyanin, allophycocyanin, etc. This extract was chosen because of its high adaptability, which reflects its resolute genetic composition. The proactive roles of cyanobacteria, particularly in the medical field, have been discussed in this review, including the history, previous food and drug administration (FDA) reports, health benefits and the various dose-dependent therapeutic functions that A. platensis possesses, including its role in fighting against lethal diseases such as cancer, SARS-CoV-2/COVID-19, etc. However, the remedy will not present its maximal effect without the proper delivery to the targeted place for deposition. The goal of this research is to maximize the bioavailability and delivery efficiency of A. platensis constituents through selected sites for effective therapeutic outcomes. The solutions reviewed are mainly on parenteral and tablet formulations. Moreover, suggested enteric polymers were discussed with minor composition variations applied for better storage in high humid countries alongside minor variations in the polymer design were suggested to enhance the premature release hindrance of basic drugs in low pH environments. In addition, it will open doors for research in delivering active pharmaceutical ingredients (APIs) in femtoscale with the use of various existing and new formulations.Abbrevations: SDGs; Sustainable Development Goals, IL-4; Interleukin-4, HDL; High-Density Lipoprotein, LDL; Low-Density Lipoprotein, VLDL; Very Low-Density Lipoprotein, C-PC; C-Phycocyanin, APC; Allophycocyanin, PE; Phycoerythrin, COX-2; Cyclooxygenase-2, RCTs; Randomized Control Trials, TNF-α; Tumour Necrosis Factor-alpha, γ-LFA; Gamma-Linolenic Fatty Acid, PGs; Polyglycans, PUFAs: Polyunsaturated Fatty Acids, NK-cell; Natural Killer Cell, FDA; Food and Drug Administration, GRAS; Generally Recognized as Safe, SD; Standard Deviation, API; Active Pharmaceutical Ingredient, DW; Dry Weight, IM; Intramuscular, IV; Intravenous, ID; Intradermal, SC; Subcutaneous, AERs; Adverse Event Reports, DSI-EC; Dietary Supplement Information Executive Committee, cGMP; Current Good Manufacturing Process, A. platensis; Arthrospira platensis, A. maxima; Arthrospira maxima, Spirulina sp.; Spirulina species, Arthrospira; Spirulina, Tecuitlatl; Spirulina, CRC; Colorectal Cancer, HDI; Human Development Index, Tf; Transferrin, TfR; Transferrin Receptor, FR; Flow Rate, CPP; Cell Penetrating Peptide, SUV; Small Unilamenar Vesicle, LUV; Large Unilamenar Vesicle, GUV; Giant Unilamenar Vesicle, MLV; Multilamenar Vesicle, COVID-19; Coronavirus-19, PEGylated; Stealth, PEG; Polyethylene Glycol, OSCEs; Objective Structured Clinical Examinations, GI; Gastrointestinal Tract, CAP; Cellulose Acetate Phthalate, HPMCP, Hydroxypropyl Methyl-Cellulose Phthalate, SR; Sustained Release, DR; Delay Release, Poly(MA-EA); Polymethyl Acrylic Co-Ethyl Acrylate, f-DR L-30 D-55; Femto-Delay Release Methyl Acrylic Acid Co-Ethyl Acrylate Polymer, MW; Molecular Weight, Tg; Glass Transition Temperature, SN2; Nucleophilic Substitution 2, EPR; Enhance Permeability and Retention, VEGF; Vascular Endothelial Growth Factor, RGD; Arginine-Glycine-Aspartic Acid, VCAM-1; Vascular Cell Adhesion Molecule-1, P; Coefficient of Permeability, PES; Polyether Sulfone, pHe; Extracellular pH, ζ-potential; Zeta potential, NTA; Nanoparticle Tracking Analysis, PB; Phosphate Buffer, DLS; Dynamic Light Scattering, AFM; Atomic Force Microscope, Log P; Partition Coefficient, MR; Molar Refractivity, tPSA; Topological Polar Surface Area, C log P; Calculated Partition Coefficient, CMR; Calculated Molar Refractivity, Log S; Solubility Coefficient, pka; Acid Dissociation Constant, DDAB; Dimethyl Dioctadecyl Ammonium Bromide, DOPE; Dioleoylphosphatidylethanolamine, GDP; Good Distribution Practice, RES; Reticuloendothelial System, PKU; Phenylketonuria, MS; Multiple Sclerosis, SLE; Systemic Lupus Erythematous, NASA; National Aeronautics and Space Administration, DOX; Doxorubicin, ADRs; Adverse Drug Reactions, SVM; Support Vector Machine, MDA; Malondialdehyde, TBARS; Thiobarbituric Acid Reactive Substances, CRP; C-Reactive Protein, CK; Creatine Kinase, LDH; Lactated Dehydrogenase, T2D; Type 2 Diabetes, PCB; Phycocyanobilin, PBP; Phycobiliproteins, PEB; Phycoerythrobilin, DPP-4; Dipeptidyl Peptidase-4, MTT; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide, IL-2; Interleukin-2, IL-6; Interleukin-6, PRISMA; Preferred Reporting Items for Systematic Reviews and Meta-Analyses, STATA; Statistics, HepG2; Hepatoblastoma, HCT116; Colon Cancer Carcinoma, Kasumi-1; Acute Leukaemia, K562; Chronic Leukaemia, Se-PC; Selenium-Phycocyanin, MCF-7; Breast Cancer Adenocarcinoma, A375; Human Melanoma, RAS; Renin-Angiotensin System, IQP; Ile-Gln-Pro, VEP; Val-Glu-Pro, Mpro; Main Protease, PLpro; Papin-Like Protease, BMI; Body Mass Index, IC50; Inhibitory Concentration by 50%, LD50; Lethal Dose by 50%, PC12 Adh; Rat Pheochromocytoma Cells, RNS; Reactive Nitrogen Species, Hb1Ac; hemoglobin A1c.

Increase awareness of the impact and multi-disciplinary up-to-date roles of A. platensis on human lives and the importance of having further research on microalgae.Soliciting a critical analysis study on A. platensis biocomposition for drug delivery research.Insights on the correlation between ionization and drug bioavailability in specific sites in the human body.Offering solutions for improvising an optimized 'Advanced Spirulina Dosage Forms' products to maximize A. platensis therapeutic/pharmacological outcomes.Insights on existing biomaterials for optimization.

A Needle-Free Jet Injection System for Controlled Release and Repeated Biopharmaceutical Delivery.

Swift vaccination is necessary as a response to disease outbreaks and pandemics; otherwise, the species under attack is at risk of a high fatality rate or even mass extinction. Statistics suggest that at least 16 billion injections are administered worldwide every year. Such a high rate of needle/syringe injection administration worldwide is alarming due to the risk of needle-stick injuries, disease spread due to cross-contamination and the reuse of needles, and the misuse of needles. In addition, there are production, handling, and disposal costs. Needle phobia is an additional issue faced by many recipients of injections with needles. In addition to a detailed literature review highlighting the need for needle-free injection systems, a compressed air-driven needle-free jet injection system with a hydro-pneumatic mechanism was designed and developed by employing an axiomatic design approach. The proposed injection system has higher flexibility, uninterrupted force generation, and provides the possibility of delivering repeated injections at different tissue depths from the dermis to the muscle (depending on the drug delivery requirements) by controlling the inlet compressed air pressure. The designed needle-free jet injector consists of two primary circuits: the pneumatic and the hydraulic circuit. The pneumatic circuit is responsible for driving, pressurizing, and repeatability. The hydraulic circuit precisely injects and contains the liquid jet, allowing us to control the volume of the liquid jet at elevated pressure by offering flexibility in the dose volume per injection. Finally, in this paper we report on the successful design and working model of an air-driven needle-free jet injector for 0.2-0.5 mL drug delivery by ex vivo experimental validation.

Metal-organic frameworks encapsulated with an anticancer compound as drug delivery system: Synthesis, characterization, antioxidant, anticancer, antibacterial, and molecular docking investigation

Metal organic framework (MOF) hybrid materials could be one of the answers in this investigation. We describe a simple and effective encapsulation of doxorubicin (DOX), an anticancer drug, inside Zr-MOF, which have been little studied as drug delivery organizations. We investigated the measured release of the drug from Zr-MOF in response to external incentives such as pH changes and interaction with biomimetic schemes. Zr-MOF with encapsulated doxorubicin (DOX@Zr-MOF) can be manufactured in one pot by addition the anticancer medication DOX to the reaction combination. They demonstrated pH-responsive medication release and cancer cell killing capability. MOFs can be designed as multifunctional distribution vehicles for a diversity of loads, including medicinal and imaging agents, using our simple one-pot approach. Fourier transform infrared (FTIR), X-ray diffraction, scanning electron microscopy, and N-2 sorption isotherm were used to analyze MOF and the developed drug delivery (DOX@Zr-MOF) scheme. It investigated the effects of MOF and a bespoke drug delivery system on the feasibility of patient breast as well as liver tumor cell lines. At pH 5, the trapped drug can be released more quickly than at pH 7.4. Zr-MOF nanoparticles had modest cytotoxicity;however, DOX@Zr-MOF has higher cytotoxicity in MCF-7 and HepG-2 cells than DOX at concentrations greater than 31.25 mu g ml(-1). These results were discovered that DOX@Zr-MOF could be a promising technique for delivering medicines to cancer cells. Furthermore, using the agar well dispersion technique, Zr-MOF, DOX, and captured DOX@Zr-MOF samples were assessed for their potential antibacterial activity against pathogenic bacteria in comparison to traditional antibiotics. In compared to the reference medication Gentamycin, the DOX@Zr-MOF exhibits a large inhibitory zone against Gram negative organisms (Escherichia coli). The docking active place interactions were assessed to see if DOX might bind to the breast cancer 3hb5-oxidoreductase receptor, prostate cancer protein 2q7k, and SARS-CoV-2 protease 6YB7 for anticancer and anticovid-19 activities.

Solid Lipid Nanoparticles Produced via a Coacervation Method as Promising Carriers for Controlled Release of Quercetin.

Quercetin is a poorly water-soluble flavonoid with many benefits to human health. Besides the natural food resources that may provide Quercetin, the interest in delivery systems that could enhance its bioavailability in the human body has seen growth in recent years. Promising delivery system candidates are represented by Solid Lipid Nanoparticles (SLNs) which are composed of well-tolerated compounds and provide a relatively high encapsulation efficiency and suitable controlled release. In this study, Quercetin-loaded and negatively charged Solid Lipid Nanoparticles were synthesized based on a coacervation method, using stearic acid as a core lipid and Arabic Gum as a stabilizer. Samples were qualitatively characterized by Dynamic light scattering (DLS), Zeta Potential, Surface infrared spectroscopy (FTIR-ATR), and Time of flight secondary ion mass spectrometry (ToF-SIMS). Encapsulation efficiency, drug release, and antioxidant effect against ABTS•+ were evaluated in vitro by UV-VIS spectrophotometry.

A macrophage-targeted platform for extending drug dosing with polymer prodrugs for pulmonary infection prophylaxis.

Pulmonary melioidosis is a bacterial disease with high morbidity and a mortality rate that can be as high as 40% in resource-poor regions of South Asia. This disease burden is linked to the pathogen's intrinsic antibiotic resistance and protected intracellular localization in alveolar macrophages. Current treatment regimens require several antibiotics with multi-month oral and intravenous administrations that are difficult to implement in under-resourced settings. Herein, we report that a macrophage-targeted polyciprofloxacin prodrug acts as a surprisingly effective pre-exposure prophylactic in highly lethal murine models of aerosolized human pulmonary melioidosis. A single dose of the polymeric prodrug maintained high lung drug levels and targeted an intracellular depot of ciprofloxacin to the alveolar macrophage compartment that was sustained over a period of 7 days above minimal inhibitory concentrations. This intracellular pharmacokinetic profile provided complete pre-exposure protection in a BSL-3 model with an aerosolized clinical isolate of Burkholderia pseudomallei from Thailand. This total protection was achieved despite the bacteria's relative resistance to ciprofloxacin and where an equivalent dose of pulmonary-administered ciprofloxacin was ineffective. For the first time, we demonstrate that targeting the intracellular macrophage compartment with extended antibiotic dosing can achieve pre-exposure prophylaxis in a model of pulmonary melioidosis. This fully synthetic and modular therapeutic platform could be an important therapeutic approach with new or re-purposed antibiotics for melioidosis prevention and treatment, especially as portable inhalation devices in high-risk, resource-poor settings.

Overcoming the paracetamol dose challenge with wrinkled mesoporous carbon spheres.

Paracetamol is the most commonly used antipyretic and analgesic drug in the world. The key challenge in paracetamol therapy is associated with the frequency of the dosing. Depending on the gastric filling within 10-20 min paracetamol is released and rapidly absorbed from the gastrointestinal tract. Therefore, it must be taken three or four times a day. To address the dose challenge it is desirable that the paracetamol release profile follows the zero-order kinetic model (constant rate of drug release per unit time). This goal can be achieved by using a suitable porous carrier system. Herein, non-toxic wrinkled mesoporous carbons with unique morphology were synthesized via the hard template method as new carriers for paracetamol. These particles can precisely modulate the release of paracetamol over 24 h in a simulated gastric fluid according to the zero-order kinetic model completely eliminating the initial burst release. Overall, these systems could significantly enhance the bioavailability of paracetamol and prolong its therapeutic effect in numerous diseases such as cold, flu, COVID-19, and severe pain.

Pharmaceutical assessment of polyvinylpyrrolidone (PVP): As excipient from conventional to controlled delivery systems with a spotlight on COVID-19 inhibition.

Polyvinylpyrrolidone (PVP) is a water-soluble polymer obtained by polymerization of monomer N-vinylpyrrolidone. PVP is an inert, non-toxic, temperature-resistant, pH-stable, biocompatible, biodegradable polymer that helps to encapsulate and cater both hydrophilic and lipophilic drugs. These advantages enable PVP a versatile excipient in the formulation development of broad conventional to novel controlled delivery systems. PVP has tunable properties and can be used as a brace component for gene delivery, orthopedic implants, and tissue engineering applications. Based on different molecular weights and modified forms, PVP can lead to exceptional beneficial features with varying chemical properties. Graft copolymerization and other techniques assist PVP to conjugate with poorly soluble drugs that can inflate bioavailability and even introduces the desired swelling tract for their control or sustained release. The present review provides chemistry, mechanical, physicochemical properties, evaluation parameters, dewy preparation methods of PVP derivatives intended for designing conventional to controlled systems for drug, gene, and cosmetic delivery. The past and growing interest in PVP establishes it as a promising polymer to enhance the trait and performance of current generation pharmaceutical dosage forms. Furthermore, the scrutiny explores existing patents, marketed products, new and futuristic approaches of PVP that have been identified and scope for future development, characterization, and its use. The exploration spotlights the importance and role of PVP in the design of Povidone-iodine (PVP-I) and clinical trials to assess therapeutic efficacy against the COVID-19 in the current pandemic scenario.

Synthesis and characterization of novel organo-hydrogel based agar, glycerol and peppermint oil as a natural drug carrier/release material.

The very recent Covid-19 pandemic has made the need to understand biocompatible polymers as support material in drug delivery systems and controlled release clearer, especially for organo-hydrogels. This study aims to synthesize various new polymeric materials called gels, hydrogels, and organo-hydrogels according to the monomer used and to investigate their use as drug release systems. The agar-glycerol (AG) pair was used to synthesize the polymers, N, N, methylene bisacrylamide (MBA, m) and glutaraldehyde (GA, g) were used as cross-linkers and peppermint oil (PmO) was included to obtain the organo-hydrogels. Therefore, one AG gel and two p (AG-m) and p (GA-g) hydrogels were synthesized within the scope of the study. Six different organo-hydrogels based on p(AG-m-PmO) or p (AG-g-PmO) were also synthesized by varying the amount of peppermint oil. Paracetamol and carboplatin were selected as the sample drugs. Synthesized gels, hydrogels and organo-hydrogels were characterized by FTIR and SEM analysis. Additionally, swelling behaviors of the synthesized gels were investigated in different media (ID water, tap water, ethanol, acetone, ethanol/ID water (1:1), acetone/ID water (1:1) and gasoline) and at different pHs. Moreover, it was determined that organo-hydrogels were blood compatible and had antioxidant properties based on hemolysis, blood clotting and antioxidant analysis. Therefore, the release of paracetamol (a known antipyretic-painkiller, recommended and used in the treatment of Covid-19) and carboplatin (widely used in cancer treatment) were studied. Evidently, as the amount of PMO oil increases, the -OH groups in organo-hydrogels will increase and the chemical and physical bonding rates will increase; therefore it was observed that increasing peppermint oil in the organo-hydrogels structure to 0.3 mL stimulated the release of the drugs. For instance, maximum paracetamol release amount from p(AG-g-PmO) and p(AG-m-PmO) organo-hydrogels was calculated to be 72.3% at pH 7.4 and 69.8% at pH 2.0, respectively. The maximum carboplatin release amount from p(AG-g-PmO) and p(AG-m-PmO) organo-hydrogels was calculated to be 99.7% at pH 7.4 and 100% at pH 7.4, respectively. It was concluded that the synthesized organo-hydrogels might easily be used as drug carrier and controlled drug release materials.

From micro to nano: evolution and impact of drug delivery in treating disease.

Over the past 50 years, drug delivery breakthroughs have enabled the approval of several important medicines. Often, this path starts with innovation from academic collaborations amongst biologists, chemists, and engineers, followed by the formation of a start-up company driving clinical translation and approval. An early wave featured injectable (i.e., intramuscular, subcutaneous) biodegradable polymeric microspheres to control drug release profiles for peptides and small molecules (e.g., Lupron Depot®, Risperdal Consta®). With these early successes for microspheres, research shifted to exploring systemic delivery by intravenous injection, which required smaller particle sizes and modified surface properties (e.g., PEGylation) to enable long circulation times. These new innovations resulted in the nanoparticle medicines Doxil® and Abraxane®, designed to improve the therapeutic index of cytotoxic cancer agents by decreasing systemic exposure and delivering more drug to tumors. Very recently, the first siRNA lipid nanoparticle medicine, Patisiran (Onpattro®), was approved for treating hereditary transthyretin-mediated amyloidosis. In this inspirational note, we will highlight the technological evolution of drug delivery from micro- to nano-, citing some of the approved medicines demonstrating the significant impact of the drug delivery field in treating many diseases.