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To introduce products in the US market, pharmaceutical companies must first obtain FDA clearance. Manufacturers might recall a product if it poses a risk of damage or violates FDA regulations. This study investigates the types, causes and consequences of recalls, as well as FDA participation and suitable recall strategies. We relied on the FDA website to gather recall data sets from 2012 to 2023, collecting information on the date of issuance, company and type of violation. The most frequent causes for recalls were sterility issues and inadequate compliance with current good manufacturing practices (cGMP). An examination of sterility recalls revealed two primary causes: a lack of assurance in sterility (accounting for 48% of recalls) and instances of non-sterility (making up 45% of recalls). A thorough examination of cGMP recalls revealed five primary types of violations: process control issues, inadequate storage practices, manufacturing problems, the presence of nitroso-amine impurities and concerns regarding stability. The findings demonstrate that sterility and cGMP compliance are FDA priorities. Pharmaceutical companies must, therefore, enhance quality compliance and create effective quality management systems that oversee the manufacturing process, quality control, personnel training and documentation to avoid these recalls. Companies should establish an internal compliance checklist and be prepared for the rectification process., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The development of vaccines has had a crucial role in preventing and controlling infectious diseases on a global scale. Innovative formulations of biomimetic vaccines inspired by natural defense mechanisms combine long-term antigen stability, immunogenicity, and targeted delivery with sustained release. Types of biomimetic nanoparticle (NP) include bacterial outer membrane vesicles (OMVs), cell membrane-decorated NPs, liposomes, and exosomes. These approaches have shown potential for cancer immunotherapy, and in antibacterial and antiviral applications. Despite current challenges, nanovaccines have immense potential to transform disease prevention and treatment, promising therapeutic approaches for the future. In this review, we highlight recent advances in biomimetic vaccine design, mechanisms of action, and clinical applications, emphasizing their role in personalized medicine, targeted drug delivery, and immunomodulation., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

As extracellular vesicle (EV)-based nanotechnology has developed rapidly, it has made unprecedented opportunities for nanomedicine possible. EVs and exosome-like nanovesicles (ELNVs) are natural nanocarriers with unique structural, compositional, and morphological characteristics that provide excellent physical, chemical, and biochemical properties. In this literature, we examine the characteristics of EVs, including how they are administered orally and their therapeutic activity. According to the current examples of EVs and ELNVs for oral delivery, milk and plant EVs can exert therapeutic effects through their protein, nucleic acid, and lipid components. Furthermore, several methods for loading drugs into exosomes and targeting exosomes have been employed to investigate their therapeutic capability. Moreover, we discuss EVs as potential drug carriers and the potential role of ELNVs for disease prevention and treatment or as potential drug carriers in the future. In conclusion, the issues associated with the development of EVs and ELNVs from sources such as milk and plants, as well as concerns with standardized applications of these EVs, are discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mondal, Pillarisetti, Junnuthula, Surwase, Hwang, Park and Lee.)

Tuberculosis (TB) remains a significant global health challenge, necessitating innovative approaches for effective treatment. Conventional TB therapy encounters several limitations, including extended treatment duration, drug resistance, patient noncompliance, poor bioavailability, and suboptimal targeting. Advanced drug delivery strategies have emerged as a promising approach to address these challenges. They have the potential to enhance therapeutic outcomes and improve TB patient compliance by providing benefits such as multiple drug encapsulation, sustained release, targeted delivery, reduced dosing frequency, and minimal side effects. This review examines the current landscape of drug delivery strategies for effective TB management, specifically highlighting lipid nanoparticles, polymer nanoparticles, inorganic nanoparticles, emulsion-based systems, carbon nanotubes, graphene, and hydrogels as promising approaches. Furthermore, emerging therapeutic strategies like targeted therapy, long-acting therapeutics, extrapulmonary therapy, phototherapy, and immunotherapy are emphasized. The review also discusses the future trajectory and challenges of developing drug delivery systems for TB. In conclusion, nanomedicine has made substantial progress in addressing the challenges posed by conventional TB drugs. Moreover, by harnessing the unique targeting abilities, extended duration of action, and specificity of advanced therapeutics, innovative solutions are offered that have the potential to revolutionize TB therapy, thereby enhancing treatment outcomes and patient compliance., (© 2023. The Author(s).)

The current study aimed to overcome the poor solubility and colon-specific delivery of curcumin (CUR) by formulating a curcumin nanosuspension (CUR-NS) using the antisolvent precipitation method. Freeze-dried CUR-NS was encapsulated into microbeads (CUR-NS-MB) by the ionotropic gelation method using zinc chloride (as a cross-linking agent) with the help of rate-controlling polymers, pectin, and chitosan. Furthermore, cellulose acetate phthalate (CAP) is incorporated as an enteric polymer to protect against acidic medium degradation. Particle size, surface morphology, interaction studies, and entrapment studies were performed to optimize CUR-NSs. Nanosuspensions stabilized with hydroxypropyl methylcellulose (HPMC E-15; 1 % w/v) showed an average particle size of 193.5 ± 4.31 nm and a polydispersity index (PDI) of 0.261 ± 0.020. The optimized microbeads (CUR-NS-MB) showed 89.45 ± 3.11 % entrapment efficiency with a drug loading of 14.54 ± 1.02 %. The optimized formulation (CUR-NS-MB) showed colon-specific in vitro drug release bypassing acid pH degradation. In animal studies, a 2.5-fold increase in C max and a 4.4-fold increase in AUC 0 48h were observed with CUR-NS-MB, which was more significant than that of plain CUR. Therefore, the developed CUR-NS-MB has the potential to be used as a colon-specific delivery system., Competing Interests: Declaration of competing interest The authors reveal no potential conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Cystic fibrosis (CF), a fatal genetic condition, causes thick, sticky mucus. It also causes pancreatic dysfunction, bacterial infection, and increased salt loss. Currently available treatments can improve the patient's quality of life. Drug delivery aided by nanotechnology has been explored to alter the pharmacokinetics and toxicity of drugs. In this short review, we aim to summarize various conventional formulations and highlight advanced formulations delivered via the pulmonary route for the treatment of CF. There is considerable interest in advanced drug delivery formulations addressing the various challenges posed by CF. Despite their potential to be translated for clinical use, we anticipate that a significant amount of effort may still be required for translation to the clinic., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Nanotechnology is an emerging applied science delivering crucial human interventions. Biogenic nanoparticles produced from natural sources have received attraction in recent times due to their positive attributes in both health and the environment. It is possible to produce nanoparticles using various microorganisms, plants, and marine sources. The bioreduction mechanism is generally employed for intra/extracellular synthesis of biogenic nanoparticles. Various biogenic sources have tremendous bioreduction potential, and capping agents impart stability. The obtained nanoparticles are typically characterized by conventional physical and chemical analysis techniques. Various process parameters, such as sources, ions, and temperature incubation periods, affect the production process. Unit operations such as filtration, purification, and drying play a role in the scale-up setup. Biogenic nanoparticles have extensive biomedical and healthcare applications. In this review, we summarized various sources, synthetic processes, and biomedical applications of metal nanoparticles produced by biogenic synthesis. We highlighted some of the patented inventions and their applications. The applications range from drug delivery to biosensing in various therapeutics and diagnostics. Although biogenic nanoparticles appear to be superior to their counterparts, the molecular mechanism degradation pathways, kinetics, and biodistribution are often missing in the published literature, and scientists should focus more on these aspects to move them from the bench side to clinics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kulkarni, Sherkar, Shirsathe, Sonwane, Varpe, Shelke, More, Pardeshi, Dhaneshwar, Junnuthula and Dyawanapelly.)

Exosomes are endosome-derived nanovesicles involved in cellular communication. They are natural nanocarriers secreted by various cells, making them suitable candidates for diverse drug delivery and therapeutic applications from a material standpoint. They have a phospholipid bilayer decorated with functional molecules and an enclosed parental matrix, which has attracted interest in developing designer/hybrid engineered exosome nanocarriers. The structural versatility of exosomes allows the modification of their original configuration using various methods, including genetic engineering, chemical procedures, physical techniques, and microfluidic technology, to load exosomes with additional cargo for expanded biomedical applications. Exosomes show enormous potential for overcoming the limitations of conventional nanoparticle-based techniques in targeted therapy. This review highlights the exosome sources, characteristics, state of the art in the field of hybrid exosomes, exosome-like nanovesicles and engineered exosomes as potential cargo delivery vehicles for therapeutic applications., Competing Interests: Declaration of Competing Interest There are no conflicts to declare., (Copyright © 2022. Published by Elsevier B.V.)

The surface drying process is an important technology in the pharmaceutical, biomedical, and food industries. The final stage of formulation development (i.e., the drying process) faces several challenges, and overall mastering depends on the end step. The advent of new emerging technologies paved the way for commercialization. Thin film freezing (TFF) is a new emerging freeze-drying technique available for various treatment modalities in drug delivery. TFF has now been used for the commercialization of pharmaceuticals, food, and biopharmaceutical products. The present review highlights the fundamentals of TFF along with modulated techniques used for drying pharmaceuticals and biopharmaceuticals. Furthermore, we have covered various therapeutic applications of TFF technology in the development of nanoformulations, dry powder for inhalations and vaccines. TFF holds promise in delivering therapeutics for lung diseases such as fungal infection, bacterial infection, lung dysfunction, and pneumonia.

Surgical site infections (SSIs) are mainly observed after surgeries that use biomaterials. The aim of this present work was to develop ciprofloxacin hydrochloride (CPH)-loaded gold nanoparticles. These ciprofloxacin-gold nanoparticles were coated onto a sterile surgical suture using an adsorption technique, followed by rigidization via ionotropic crosslinking using sodium alginate. Furthermore, UV-visible spectroscopy, infrared spectroscopy, and scanning electron microscopy were used to characterize the samples. The particle size of the nanoparticles was 126.2 ± 13.35 nm with a polydispersity index of 0.134 ± 0.03, indicating nanosize formation with a monodispersed system. As per the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines, stability studies were performed for 30 days under the following conditions: 2-8 °C, 25 ± 2 °C/60 ± 5% RH, and 40 ± 2 °C/75 ± 5% RH. For both Gram-negative and Gram-positive bacteria, the drug-coupled nanoparticle-laden sutures showed a twofold higher zone of inhibition compared with plain drug-coated sutures. In vitro drug release studies showed a prolonged release of up to 180 h. Hemolysis and histopathology studies displayed these sutures' acceptable biocompatibility with the healing of tissue in Albino Swiss mice. The results depict that the use of antibiotic-coated sutures for preventing surgical site infection for a long duration could be a viable clinical option.

Gliclazide (GCZ), an antidiabetic medication, has poor solubility and limited oral bioavailability due to substantial first-pass metabolism. Thus, the purpose of the current study was to optimize and formulate a GCZ nanosuspension (NS) employing the antisolvent precipitation technique. A three-factor, three-level Box-Behnken design (BBD) was used to examine the impact of the primary formulation factors (drug concentration, stabilizer, and surfactant %) on particle size. The optimized NS contains 29.6 mg/mL drug, 0.739% lecithin, and 0.216% sodium dodecyl sulfate (SDS). Under scanning microscopy, the topography of NS revealed spherical particles. Furthermore, NS had a much better saturation solubility than the pure material, which resulted in a rapid dissolving rate, which was attributed to the amorphous structure and smaller particle size of the NS particles. Studies on intestinal permeability using the in vitro noneverted intestinal sac gut method (duodenum, jejunum, and ileum) and single-pass intestinal permeability (SPIP) techniques showed that the effective permeability was also increased by more than 3 fold. In the pharmacokinetic study, the C max and AUC 0-t values of NS were approximately 3.35- and 1.9-fold higher than those of the raw medication and marketed formulation (MF). When compared to plain drug and commercial formulations, the antidiabetic efficacy of NS demonstrated that it had a significant impact on lowering glucose levels.

Solid lipid nanoparticles (SLNs) are an alternate carrier system to liposomes, polymeric nanoparticles, and inorganic carriers. SLNs have attracted increasing attention in recent years for delivering drugs, nucleic acids, proteins, peptides, nutraceuticals, and cosmetics. These nanocarriers have attracted industrial attention due to their ease of preparation, physicochemical stability, and scalability. These characteristics make SLNs attractive for manufacture on a large scale. Currently, several products with SLNs are in clinical trials, and there is a high possibility that SLN carriers will quickly increase their presence in the market. A large-scale manufacturing unit is required for commercial applications to prepare enough formulations for clinical studies. Furthermore, continuous processing is becoming more popular in the pharmaceutical sector to reduce product batch-to-batch differences. This review paper discusses some conventional methods and the rationale for large-scale production. It further covers recent progress in scale-up methods for the synthesis of SLNs, including high-pressure homogenization (HPH), hot melt extrusion coupled with HPH, microchannels, nanoprecipitation using static mixers, and microemulsion-based methods. These scale-up technologies enable the possibility of commercialization of SLNs. Furthermore, ongoing studies indicate that these technologies will eventually reach the pharmaceutical market.

With the growing burden of cancer, parallel advancements in anticancer nanotechnological solutions have been witnessed. Among the different types of cancers, breast cancer accounts for approximately 25% and leads to 15% of deaths. Nanomedicine and its allied fields of material science have revolutionized the science of medicine in the 21st century. Novel treatments have paved the way for improved drug delivery systems that have better efficacy and reduced adverse effects. A variety of nanoformulations using lipids, polymers, inorganic, and peptide-based nanomedicines with various functionalities are being synthesized. Thus, elaborate knowledge of these intelligent nanomedicines for highly promising drug delivery systems is of prime importance. Polymeric micelles (PMs) are generally easy to prepare with good solubilization properties; hence, they appear to be an attractive alternative over the other nanosystems. Although an overall perspective of PM systems has been presented in recent reviews, a brief discussion has been provided on PMs for breast cancer. This review provides a discussion of the state-of-the-art PMs together with the most recent advances in this field. Furthermore, special emphasis is placed on regulatory guidelines, clinical translation potential, and future aspects of the use of PMs in breast cancer treatment. The recent developments in micelle formulations look promising, with regulatory guidelines that are now more clearly defined; hence, we anticipate early clinical translation in the near future.

A novel stability-indicating, reversed-phase, high-performance liquid chromatography (RP-HPLC) method was developed and validated for the determination of favipiravir in an oral suspension. The effective separation of favipiravir and its degradation products was achieved on a Zorbax Eclipse Plus C18 column (5 μm particle size, 150 mm length × 4.6 mm diameter). The mobile phase was prepared by mixing 5 mM of phosphate buffer (pH 3.5) and methanol in a 75:25 v/v ratio delivered at a 1.0 mL/min flow rate. The eluents were monitored using a photodiode array detector at a wavelength of 322 nm. The stability-indicating nature of this method was evaluated by performing force degradation studies under various stress conditions, such as acidic, alkali, oxidative, thermal, and photolytic degradation. Significant degradation was observed during the alkali stress degradation condition. The degradation products generated during various stress conditions were well separated from the favipiravir peak. In addition, the major degradation product formed under alkali stress conditions was identified using UPLC-ESI-TQ-MS/MS and NMR. Method validation was performed according to the ICH Q2 (R1) guideline requirements. The developed method is simple, accurate, robust, and reliable for routine quality control analysis of favipiravir oral suspensions.

Among various drug administration routes, oral drug delivery is preferred and is considered patient-friendly; hence, most of the marketed drugs are available as conventional tablets or capsules. In such cases, the administration of drugs with or without food has tremendous importance on the bioavailability of the drugs. The presence of food may increase (positive effect) or decrease (negative effect) the bioavailability of the drug. Such a positive or negative effect is undesirable since it makes dosage estimation difficult in several diseases. This may lead to an increased propensity for adverse effects of drugs when a positive food effect is perceived. However, a negative food effect may lead to therapeutic insufficiency for patients suffering from life-threatening disorders. This review emphasizes the causes of food effects, formulation strategies to overcome the fast-fed variability, and the regulatory aspects of drugs with food effects, which may open new avenues for researchers to design products that may help to eliminate fast-fed variability.

Age-related macular degeneration (AMD) is a macular degenerative eye disease, the major cause of irreversible loss of central vision. In this review, we highlight current progress and future perspectives of novel and investigational therapeutic strategies in the drug pipeline, including anti-vascular endothelial growth factor (VEGF) agents, bispecific antibodies, biosimilars, small molecules, gene therapy, and long-acting drug delivery strategies for both dry and wet AMD. We anticipate that biologics with dual functionalities and combined therapies with long-acting capabilities will lead the wet AMD pipeline. Sustained-release platforms also show potential. However, significant breakthroughs are yet to be made for dry AMD. The personalized approach might be well suited in the scenario of diverse genetic variations in both conditions., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Naringenin (NRG) is a flavonoid and has been reported as an anti-osteoporotic agent. However, poor bioavailability may limit the anti-osteoporotic potential of the drug. The purpose of the study was to compare the anti-osteoporotic activity of naringenin nanosuspension (NRG-NS) with the NRG and standard therapeutic drug, raloxifene hydrochloride (RLX). Here, NRG-NS showed anti-osteoporotic activity in MG-63 cells by upregulating the osteocalcin levels. The in vivo anti-osteoporotic activity of NRG-NS was further investigated in an osteoporotic rat model to mimic the post-menopausal condition. The animals were randomized and separated into six groups. The animals were treated with RLX (p.o., 5.4 mg/kg), NRG (p.o., 20 mg/kg), NRG-NS (p.o., 20 mg/kg), and blank-NS for 60 days after completion of a 30-day post-surgery period and compared with control and ovariectomized (OVX) groups. After the treatment, body and uterine weights, biochemical estimation in serum (calcium, phosphorus, acid phosphatase, alkaline phosphatase, osteocalcin), bone parameters (length, diameter, dry weight, density, ash weight, bone mineral content) and bone microarchitecture by histopathology were determined. The results showed the protective effects of NRG-NS on osteoblast-like MG-63 cells. The biochemical estimations confirmed the normalization of parameters viz., alkaline phosphatase, calcium concentrations, and bone density with a decrease in levels of acid phosphatase and inorganic phosphorus with NRG-NS as compared to plain NRG. The results indicated that the oral administration of NRG-NS could be a potential therapeutic formulation for the treatment of osteoporosis.

The purpose of our study was to improve the solubility, bioavailability, and efficacy of zotepine (ZTP) by brain-targeted intranasal delivery of microemulsion (ME) and its physicochemical properties, the pharmacokinetic and pharmacodynamic parameters were evaluated. The optimized ME formulations contain 10% w/w of oil (Capmul MCM C8, monoglycerides, and diglycerides of caprylic acid), 50% w/w of S mix (Labrasol and Transcutol HP, and 40% w/w of water resulting in a globule size of 124.6 ± 3.52 nm with low polydispersity index (PDI) (0.212 ± 0.013) and 2.8-fold higher permeation coefficient through porcine nasal mucosa compared to pure drug). In vitro cell line studies on RPMI 2650, Beas-2B, and Neuro-2A revealed ZTP-ME as safe. ZTP-ME administered intranasally showed higher AUC 0-t24 (18.63 ± 1.33 h × µg/g) in the brain by approximately 4.3-fold than oral ME (4.30 ± 0.92 h × µg/g) and 7.7-fold than intravenous drug solutions (2.40 ± 0.36 h × µg/g). In vivo anti-schizophrenic activity was conducted using catalepsy test scores, the formulation showed better efficacy via the intranasal route; furthermore, there was no inflammation or hemorrhage in the nasal cavity. The results concluded that the ZTP microemulsion as a safe and effective strategy could greatly enhance brain distribution by intranasal administration.

Among the various types of nanoparticles and their strategy for synthesis, the green synthesis of silver nanoparticles has gained much attention in the biomedical, cellular imaging, cosmetics, drug delivery, food, and agrochemical industries due to their unique physicochemical and biological properties. The green synthesis strategies incorporate the use of plant extracts, living organisms, or biomolecules as bioreducing and biocapping agents, also known as bionanofactories for the synthesis of nanoparticles. The use of green chemistry is ecofriendly, biocompatible, nontoxic, and cost-effective. We shed light on the recent advances in green synthesis and physicochemical properties of green silver nanoparticles by considering the outcomes from recent studies applying SEM, TEM, AFM, UV/Vis spectrophotometry, FTIR, and XRD techniques. Furthermore, we cover the antibacterial, antifungal, and antiparasitic activities of silver nanoparticles.

Age-related macular degeneration (AMD) is the leading cause of vision loss in geriatric population. Intravitreal (IVT) injections are popular clinical option. Biologics and small molecules offer efficacy but relatively shorter half-life after intravitreal injections. To address these challenges, numerous technologies and therapies are under development. Most of these strategies aim to reduce the frequency of injections, thereby increasing patient compliance and reducing patient-associated burden. Unlike IVT frequent injections, molecular therapies such as cell therapy and gene therapy offer restoration ability hence gained a lot of traction. The recent approval of ocular gene therapy for inherited disease offers new hope in this direction. However, until such breakthrough therapies are available to the majority of patients, antibody therapeutics will be on the shelf, continuing to provide therapeutic benefits. The present review aims to highlight the status of pre-clinical and clinical studies of neovascular AMD treatment modalities including Anti-VEGF therapy, upcoming bispecific antibodies, small molecules, port delivery systems, photodynamic therapy, radiation therapy, gene therapy, cell therapy, and combination therapies.

Posterior eye tissues, such as retina, are affected in many serious eye diseases, but drug delivery to these targets is challenging due to various anatomical eye barriers. Intravitreal injections are widely used, but the intervals between invasive injections should be prolonged. We synthesized and characterized ( 1 H NMR, gel permeation chromatography) block copolymers of poly(ethylene glycol), poly(caprolactone), and trimethylene carbonate. These polymers self-assembled to polymersomes and polymeric micelles. The mean diameters of polymersomes and polymeric micelles, about 100 nm and 30-50 nm, respectively, were obtained with dynamic light scattering. Based on single particle tracking and asymmetric flow field-flow fractionation, the polymeric micelles and polymersomes were stable and diffusible in the vitreous. The materials did not show cellular toxicity in cultured human umbilical vein endothelial cells in the Alamar Blue Assay. Pharmacokinetics of the intravitreal nanocarriers in the rabbits were evaluated using in vivo fluorophotometry. The half-lives of the polymersomes (100 nm) and the micelles (30 nm) were 11.4-32.7 days and 4.3-9.5 days. The intravitreal clearance values were 1.7-8.7 µL/h and 3.6-5.4 µL/h for polymersomes and polymeric micelles, respectively. Apparent volumes of distribution of the particles in the rabbit vitreous were 0.6-1.3 mL for polymeric micelles and 1.9-3.4 mL for polymersomes. Polymersomes were found in the vitreous for at least 92 days post-dosing. Furthermore, fundus imaging revealed that the polymersomes accumulated near the optic nerve and retained there even at 111 days post-injection. Polymersomes represent a promising technology for controlled and site-specific drug delivery in the posterior eye segment.

Nanoparticle morphology (size, shape, and composition) and surface chemistry are the determining factors underpinning the efficacy of such materials in therapeutic applications. The size, shape, and surface chemistry of a nanoparticle can strongly influence key properties such as interactions with diverse biological fluids and interfaces and, in turn, impact the delivery of bioactive cargo, modulating therapeutic performance. This is exemplified in ocular drug delivery, where potential therapeutics must navigate complex biological media such as the gel-like vitreal fluid and the retina. Biodegradable block copolymer amphiphiles are a robust tool for the engineering of various types of self-assembled nanoparticles with diverse morphologies ranging from spherical and tubular polymersomes to spherical and worm-like micelles. Here, we explore the effect of morphological features such as shape and surface chemistry upon the interactions of a series of copolymer nanoparticles with retinal (ARPE-19) cells and the release of a low solubility drug (dexamethasone) that is currently used in ocular therapy and study their diffusion in vitreous using ex vivo eyes. We demonstrate that both aspect ratio and surface chemistry of nanoparticles will influence their performance in terms of cell uptake, drug release, and diffusion with high aspect ratio shapes demonstrating enhanced properties in relation to their spherical counterparts.