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Extracellular vesicles (EVs) are a population of small vesicles secreted by essentially all cell types, containing a wide variety of biological macromolecules. Due to their intrinsic capabilities for efficient intercellular communication, they are involved in various aspects of cellular functioning. In the past decade, EVs derived from stem cells attracted interest in the field of regenerative medicine. Owing to their regenerative properties, they have great potential for use in tissue repair, in particular for tissues with limited regenerative capabilities such as cartilage. The maintenance of articular cartilage is dependent on a precarious balance of many different components that can be disrupted by the onset of prevalent rheumatic diseases. However, while cartilage is a tissue with strong mechanical properties that can withstand movement and heavy loads for years, it is virtually incapable of repairing itself after damage has occurred. Stem cell-derived EVs (SC-EVs) transport regenerative components such as proteins and nucleic acids from their parental cells to recipient cells, thereby promoting cartilage healing. Many possible pathways through which SC-EVs execute their regenerative function have been reported, but likely there are still numerous other pathways that are still unknown. This review discusses various preclinical studies investigating intra-articular injections of free SC-EVs, which, while often promoting chondrogenesis and cartilage repair in vivo, showed a recurring limitation of the need for multiple administrations to achieve sufficient tissue regeneration. Potentially, this drawback can be overcome by making use of an EV delivery platform that is capable of sustainably releasing EVs over time. With their remarkable versatility and favourable chemical, biological and mechanical properties, hydrogels can facilitate this release profile by encapsulating EVs in their porous structure. Ideally, the optimal delivery platform can be formed in-situ, by means of an injectable hydrogel that can be administered directly into the affected joint. Relevant research fulfilling these criteria is discussed in detail, including the steps that still need to be taken before injectable hydrogels for sustained delivery of EVs can be applied in the context of cartilage regeneration in the clinic.

Designing stimuli-responsive therapeutic scaffolds to deliver hydrophobic chemo drugs with controlled and sustained release at the tumour site would be promising in cancer treatment. In a quest for the stimuli-responsive drug delivery system with sustained release, herein we have fabricated active pharmaceutical ingredient based ionic liquid (IL) based hydrogel with self-healable and injectable properties. The ionic hydrogel makes a localized, long-term co-delivery system with self-healable, injectable, and stimuli-responsiveness. Further, the smart hybrid ionic hydrogel was constructed through encapsulating doxorubicin (DOX) within the 3D matrix of the ionic hydrogel, which responds to an intracellular biological stimulus (e.g., pH and temperature) and releases the DOX in 57 h. Experimental results of IL-IL, IL-DOX interactions are supported through Density Functional Theory (DFT) calculations. In vitro cellular studies revealed that DOX loaded hybrid ionic hydrogel shows a synergistic anticancer effect against MCF-07 cells. These results demonstrate the ability of the ionic hydrogel as a promising candidate for local cancer therapeutics.

Aim: A polymeric in situ gelling delivery system for localized and sustained delivery to jawbone infections was developed. Materials & methods: In situ gelling delivery systems were prepared using either Poly(dl-lactic acid) or chitosan and Pluronic F127/Pluronic F68. Metronidazole nanoparticles were prepared using poly(dl-lactide-co-glycolide) or chitosan. Poly(dl-lactide-co-glycolide) was used for microparticles. Particles were characterized for size, charge and morphology. Results: Viscosity and yield stress of the gels were 0.4 Pa.s and 2 Pa, respectively, with 70% cell viability over 72 h. Around 90% of loaded metronidazole was released at a sustained rate over 1 week. Conclusion: Use of appropriate amount of nano/microparticles in the gel resulted in a sustained release over a period of 1 week – needed for jawbone infection.

Background: To understand the clinical practice pattern of general ophthalmologists in the management of retinal diseases. Also, aimed to explore the ophthalmologist’s perspective towards patient compliance and unmet need in the management of neovascular age-related macular degeneration (nAMD). Materials and Methods: A total of 108 ophthalmologists participated in this cross-sectional questionnaire-based survey. A paper-based questionnaire with a tool of twelve questions, with response options ranging on a five-point Likert scale of ‘strongly agree’ to ‘strongly disagree’ was provided to participants. Results: Out of 108, 95.4% ophthalmologists confirmed that they were commonly consulted for nAMD amongst the different retinal disorders (RDs). The majority of respondents (87%) confirmed that 60% or fewer patients continue the treatment for a year. About 81.5% of ophthalmologists stated that fluid (Intra-retinal fluid, Sub-retinal fluid) on optical coherence tomography (OCT) was an extremely important parameter for disease activity. The survey revealed that injection frequency was the factor for non-compliance in majority of (>50%) patients. More than 64% of respondents opined that improved efficacy (70.4%), reduced treatment burden (64.8%), and longer acting agents/sustained delivery (64.8%) are the most critical unmet needs for nAMD patients. Conclusion: Based on the findings, it can be concluded that, in addition to functional outcomes i.e. visual acuity, ophthalmologists also considered retinal fluid and central retinal thickness as important parameters for treatment-related decisions. Ophthalmologists suggested that there is a need to develop longer-acting agents with improved efficacy which may help in reducing treatment burden in nAMD management. Key Message: Longer acting anti-vascular endothelial growth factor (VGEF) agents with improved efficacy may help in reducing the treatment burden in nAMD management. Keywords: Neovascular age- related ma

Background The current relevance of functional foods in human health and well-being has led to an increased interest in developing new types of oral administration systems for probiotics and nutraceuticals. Encapsulation may provide protection and sustained delivery in food formulations. Scope and approach The recent discussions about probiotics encapsulation for application in both nutraceutical and food sectors are addressed. The topics approached include encapsulation systems, nutraceuticals and probiotics concepts and current market situation, microbial microencapsulation, and food applications for beyond their use in the pharmaceutical industry. Studies analyzing the viability and stability of encapsulated probiotics applied in food matrices are presented and discussed as well. Key findings and conclusions This review sought to present the most recent discussions regarding the nano/microencapsulation of nutraceuticals and probiotics process for application in food products. Although many protocols found in the scientific literature are not viable for commercial applications, some formulations can be employed in food systems. In addition, in vivo human studies are extremely necessary to prove the effectiveness of such formulations.

Biomaterial implants for the sustained delivery of therapeutics can be utilized to deliver drugs at near-constant rates over extended time frames to provide an alternative to daily oral medications. The biomaterials used to construct these systems, however, are often not bioresorbable and thus require a secondary surgery for removal from the body, and fabrication of these systems may require the use of harsh chemical solvents. To address these shortcomings, a fabrication process was developed to generate biodegradable drug reservoir systems from regenerated silk fibroin protein solution (23% w/v). The tubular systems, with an inner diameter of 2.0 mm and wall thickness < 250µm, were developed using an all-aqueous solution-gel-solid phase transition curing process. Two different clinically-relevant therapeutics were released at near-constant rates for 30 days (> 100µg/day). The protein secondary structure of the devices consisted of 40% crystalline beta sheet. Mechanically, radial compression (1mm/min) of unloaded systems demonstrated Young’s moduli similar to cancellous (spongy) bone (100 to 250 MPa) and the systems showed good recovery under cyclic compression (to 17.5% strain). The devices could be generated in complex shapes (e.g., hollow cylinders) via an additive molding process, offering the potential for drug delivery but also for broader applications in tissue engineering and diagnostics.

Susanne B Haga, Rachel Mills, Jivan Moaddeb, Yiling Liu, Deepak Voora Center for Applied Genomics & Precision Medicine, Durham, NC, 27708, USACorrespondence: Susanne B HagaCenter for Applied Genomics & Precision Medicine, 101 Science Drive, Box 3382, Durham, NC, 27708 Tel +919-684-0325Email susanne.haga@duke.eduObjective: This study assessed pharmacist experiences with delivering pharmacogenetic (PGx) testing in independent community pharmacies.Methods: We conducted a cluster randomized trial of independent community pharmacies in North Carolina randomized to provide either PGx testing as a standalone service or integrated into medication therapy management (MTM) services. Surveys and pharmacist data about the delivery of PGx testing were collected. Semi-structured interviews were also conducted.Results: A total of 36 pharmacists participated in the study from 22 pharmacies. Sixteen pharmacists completed the pre-study and post-study surveys, and four pharmacists completed the semi-structured interviews. Thirty-one percent (11/36) of pharmacists had had some education in personalized medicine or PGx prior to the study. The only outcome that differed by study arm was the use of educational resources, with significantly higher utilization in the PGx testing only arm (p=0.007). Overall, compared to the pre-study assessment, pharmacists’ knowledge about PGx significantly improved post-study (p=0.018). In the post-study survey, almost all pharmacists indicated that they felt qualified/able to provide PGx testing at their pharmacy. While 75% of pharmacists indicated that they may continue to provide PGx testing at their pharmacy after the study, the major concerns were lack of reimbursement for PGx counseling and consultation given the necessary time required.Conclusion: Our findings demonstrated a positive experience with delivering PGx testing in the community pharmacy setting with little difference in pharmacists’ experiences in providing PGx testing with or without MTM. Pharmacists were confident in their ability to provide PGx testing and were interested in continuing to offer testing, though sustained delivery may be challenged by lack of prescribing provider engagement and reimbursement.Keywords: pharmacy, pharmacogenetic testing, feasibility, pharmacist experience

Most of the people in the world are affected by glaucoma, which leads to irreversible blindness. Several patient friendly treatments are available, nevertheless medications lack an easy and efficient way of sustained delivery. To make the delivery with enhanced bioavailability, biodegradable and non-biodegradable polymers-based drug carriers are explored. However, ocular drug delivery issues have not been resolved yet due to less adhesiveness, poor penetration ability, pH, and temperature dependent burst releases. Chitosan is found to be effective for ocular drug delivery due to excellent physio-chemical properties in terms of overcoming the existing issues. In this review, we aim to highlight why it has been chosen and the holy grail for ocular drug delivery. Besides, we have comprehensively reviewed recent patents on chitosan as a platform for ocular drug delivery and future perspectives on factors, lacunae and challenges that need to be addressed for better ocular delivery methods for glaucoma management.

Exopolysaccharides (EPS) are important bioproducts produced by some genera of lactic acid bacteria. EPS are famous for their shelf-life improving properties, techno-functional enhancing abilities in food and dairy industries, besides their beneficial health effects. Furthermore, exopolysaccharides have many prospective and well-established contributions in the field of drugs and diagnostic industry. In this review, classification of EPS produced by LAB was presented. Moreover, current and potential applications of EPS in food, dairy, baking industries, cereal-based, and functional products were described. Also, some clinical and pharmaceutical applications of EPS such as intelligent drug delivery systems (microsystems and nanosystems for sustained delivery), interpenetrating polymer networks (IPNs), anticancer drug-targeting, recombinant macromolecular biopharmaceuticals, gene delivery, tissue engineering, and role of EPS in diagnostics were highlighted. Finally, future prospects concerning enhancing EPS production, minimizing costs of their production, and exploring their contribution in further applications were discussed.

Acute spinal cord injury (SCI) is a devastating condition that results in tremendous physical and psychological harm and a series of socioeconomic problems. Although neurons in the spinal cord need neurotrophic factors for their survival and development to reestablish their connections with their original targets, endogenous neurotrophic factors are scarce and the sustainable delivery of exogeneous neurotrophic factors is challenging. The widely studied neurotrophic factors such as brain-derived neurotrophic factor, neurotrophin-3, nerve growth factor, ciliary neurotrophic factor, basic fibroblast growth factor, and glial cell-derived neurotrophic factor have a relatively short cycle that is not sufficient enough for functionally significant neural regeneration after SCI. In the past decades, scholars have tried a variety of cellular and viral vehicles as well as tissue engineering scaffolds to safely and sustainably deliver those necessary neurotrophic factors to the injury site, and achieved satisfactory neural repair and functional recovery on many occasions. Here, we review the neurotrophic factors that have been used in trials to treat SCI, and vehicles that were commonly used for their sustained delivery., Graphical abstract

Pulmonary route of drug delivery has drawn significant attention due to the limitations associated with conventional routes and available treatment options. Drugs administered through pulmonary route has been an important research area that focuses on to developing effective therapeutic interventions for asthma, chronic obstructive pulmonary disease, tuberculosis, lung cancer etc. The intravenous route has been a natural route of delivery of proteins and peptides but associated with several issues including high cost, needle-phobia, pain, sterility issues etc. These issues might be addressed by the pulmonary administration of macromolecules to achieving an effective delivery and efficacious therapeutic impact. Efforts have been made to develop novel drug delivery systems (NDDS) such as nanoparticles, microparticles, liposomes and their engineered versions, polymerosomes, micelles etc to achieving targeted and sustained delivery of drug(s) through pulmonary route. Further, novel approaches such as polymer-drug conjugates, mucoadhesive particles and mucus penetrating particles have attracted significant attention due to their unique features for an effective delivery of drugs. Also, use of semi flourinated alkanes is in use for improvising the pulmonary delivery of lipophilic drugs. Present review focuses on to unravel the mechanism of pulmonary absorption of drugs for major pulmonary diseases. It summarizes the development of interventional approaches using various particulate and vesicular drug delivery systems. In essence, the orchestrated attempt presents an inflammatory narrative on the advancements in the field of pulmonary drug delivery.

Recently, naturally occurring and abundantly available halloysite nanoclay has emerged as a nanomaterial carrier system suitable for both controlled and sustained delivery. These aluminosilicate tubes of 50-nm diameter, with outer silica and inner alumina layers, possess a tubular structure, with excellent features such as large aspect ratio, good biocompatibility, and high mechanical strength entails them to be suitable for drug delivery. The unique features of these nanotubes are the ability to load DNA and enzyme due to opposite charges on both inner and outer surfaces which allow selective drug loading on both surfaces. This review article emphasizes on the drug loading techniques with release characteristics and some important applications in biomedical, environmental fields, and different types of medication. Being most versatile, these nanotubes can be used widely as a carrier system for enzyme bases and different types of the nucleus which can be a most promising step for novel drug delivery systems.

Background:Effective management of prosthetic joint infection (PJI) requires prolonged, sustained delivery of antibiotics to the effective joint space. Calcium sulphate antibiotic delivery systems have been used in this setting, however, potentially serious complications including symptomatic hypercalcaemia have been described. There is relatively little prospective data on the results with the use of these compounds.Methods:A prospective study was performed between October 2016 and June 2018. 29 patients who underwent revision total hip arthroplasty (THA) for confirmed PJI were treated with Stimulan calcium sulphate antibiotic delivery system. Laboratory blood tests including serum calcium levels, C-reactive protein (CRP) and white cell count (WBC) were monitored for 6 weeks post-surgery. Wounds were assessed for discharge and radiographs for dissolution and for signs of heterotopic ossification.Results:The mean age was 67 years and mean ASA score III. There was no significant increase between the preoperative serum calcium and those at 2 and 6 weeks. The CRP and white cell count were significantly reduced at 6 weeks. Full dissolution occurred by 6 weeks post-op. 1 patient (3.4%) had a prolonged wound discharge.Conclusions:Stimulan is a valid option for management of patients with PJI following total hip arthroplasty. Complication rates are low following its use.

Solid lipid particles have a great potential in sustained drug delivery, the lipid excipients are solid at room temperature with a slow degradation rate. Poly (D, L-lactic-coglycolic acid) (PLGA) has been successfully clinically applied for the sustained delivery of peptide drugs. A recent study showed the advantage of hybrid PLGA-lipid microparticles (MPs) over PLGA MPs for the sustained delivery of peptide drug in vivo. In this paper, we briefly present PLGA MPs, solid lipid MPs and PLGA lipid hybrid MP prepared by the double emulsion method and the spray drying method and discuss the effects of excipients on encapsulation efficiency of protein and peptide drugs in the MPs. The pros and cons of PLGA MPs, solid lipid MPs and PLGA lipid hybrid MP as carriers for sustained delivery of protein and peptide drugs are also discussed.

Recently, prebiotics are attracting plenty of attention in the field of skin care, since it is found that they are able to support the balance of beneficial and harmful microorganisms on the skin, and accordingly prevent several skin conditions associated with microbial imbalance. Topical application of prebiotics, although insufficiently investigated, holds great promise in improving skin health. The purpose of this research was to determine the prebiotic potential of galacto-oligosaccharides (GOS) for skin microbiota and suitability for incorporation in different topical formulations, and finally, provide insights into their diffusion properties.The prebiotic effect of GOS was evaluated through the influence on the growth of Staphylococcus epidermidis and Staphylococcus aureus, the most common resident and pathogenic bacterium of the skin microbiota, respectively. Also, with the future use of GOS in cosmetic products in mind, the diffusion of GOS molecules from two different topical formulations, hydrogel and oil-in-water (O/W) gel emulsion, was monitored employing Franz diffusion cell and two systems-with cellulose acetate membrane and transdermal diffusion test model, Strat-M® membrane. Course of fermentation and the amount of diffused GOS molecules were monitored using high-performance liquid chromatography (HPLC).The in vitro results revealed that GOS at a concentration of 5% (w/v) has a pronounced stimulatory effect on S. epidermidis, while simultaneously showing an inhibitory effect on S. aureus, both in nutrient broth and cosmetic formulations. GOS trisaccharide and tetrasaccharide diffusion coefficients from O/W gel emulsion were calculated to be 5.61·10When applied in adequate concentration, GOS has the potential to be used as a skin prebiotic. Novel GOS enriched formulations, Aristoflex® AVC-based hydrogel and Heliogel™-based O/W gel emulsion, provided efficient diffusion and delivery of prebiotic GOS molecules to the skin surface.Récemment, les prébiotiques attirent beaucoup d'attention dans le domaine des soins de la peau, car il a été constaté qu'ils sont capables de soutenir l'équilibre des micro-organismes bénéfiques et nocifs sur la peau et, par conséquent, de prévenir plusieurs affections cutanées associées à un déséquilibre microbien. L'application topique de prébiotiques, bien qu'insuffisamment étudiée, est très prometteuse pour améliorer la santé de la peau. Le but de cette recherche était de déterminer le potentiel prébiotique des galacto-oligosaccharides (GOS) pour le microbiote cutané et leur aptitude à être incorporés dans différentes formulations topiques, et enfin, de fournir des informations sur leurs propriétés de diffusion. MÉTHODES: L'effet prébiotique du GOS a été évalué à travers l'influence sur la croissance de Staphylococcus epidermidis et de Staphylococcus aureus, les bactéries résidentes et pathogènes les plus courantes du microbiote cutané, respectivement. De plus, en gardant à l'esprit l'utilisation future du GOS dans les produits cosmétiques, la diffusion des molécules de GOS à partir de deux formulations topiques différentes, l'hydrogel et l'émulsion de gel huile-dans-eau (H/E), a été surveillée à l'aide d'une cellule de diffusion de Franz et de deux systèmes - avec de la cellulose membrane en acétate et modèle de test de diffusion transdermique, membrane Strat-M®. Le cours de la fermentation et la quantité de molécules de GOS diffusées ont été surveillés en utilisant la chromatographie liquide à haute performance (HPLC).Les résultats in vitro ont révélé que le GOS à une concentration de 5% (p/v) a un effet stimulant prononcé sur S. epidermidis, tout en montrant simultanément un effet inhibiteur sur S. aureus, à la fois dans les bouillons nutritifs et les formulations cosmétiques. Les coefficients de diffusion GOS trisaccharide et tétrasaccharide de l'émulsion de gel H/E ont été calculés comme étant de 5,61·10Lorsqu'il est appliqué à une concentration adéquate, le GOS a le potentiel d'être utilisé comme prébiotique cutané. De nouvelles formulations enrichies en GOS, l'hydrogel à base d'Aristoflex® AVC et l'émulsion de gel H/E à base d'Heliogel™, ont permis une diffusion et une délivrance efficaces des molécules GOS prébiotiques à la surface de la peau.

Implantable drug delivery systems offer an alternative for the treatments of long-term conditions (i.e. schizophrenia, HIV, or Parkinson's disease among many others). The objective of the present work was to formulate implantable devices loaded with the model hydrophobic drug olanzapine (OLZ) using robocasting 3D-printing combined with a pre-formed rate controlling membrane. OLZ was selected as a model molecule due to its hydrophobic nature and because is a good example of a molecule used to treat a chronic condition schizophrenia. The resulting implants consisted of a poly(ethylene oxide) (PEO) implant coated with a poly(caprolactone) (PCL)-based membrane. The implants were loaded with 50 and 80% (w/w) of OLZ. They were prepared using an extrusion-based 3D-printer from aqueous pastes containing 36-38% (w/w) of water. The printing process was carried out at room temperature. The resulting implants were characterized by using infrared spectroscopy, scanning electron microscopy, thermal analysis, and X-ray diffraction. Crystals of OLZ were present in the implant after the printing process. release studies showed that implants containing 50% and 80% (w/w) of OLZ were capable of providing drug release for up to 190 days. On the other hand, implants containing 80% (w/w) of OLZ presented a slower release kinetics. After 190 days, total drug release was ca. 77% and ca. 64% for implants containing 50% and 80% (w/w) of OLZ, respectively. The higher PEO content within implants containing 50% (w/w) of OLZ allows a faster release as this polymer acts as a co-solvent of the drug.

The development of microneedle (MN)-assisted drug delivery technologies has been highly active for nearly two decades. The microneedle array patch (MAP)-based self-application technology bypasses many of the challenges associated with injectable routes by delivering the therapeutic materials directly into the intradermal space and allowing the release of the active ingredient in a sustained or controlled manner. Different types of biodegradable solid/dissolving MAP and nanoparticle-loaded/coated polymeric MAP or hollow MN have been envisioned for long-acting sustained delivery of therapeutic payloads, aiming for reducing the side effects and administration frequency to improve patient compliance. In this chapter, we covered the different types of MAPs that are loaded with different nano/biotherapeutics for long-acting delivery for a wide range of potential clinical applications. We have outlined the future development scenario for this long-acting MAP delivery system to achieve promising clinical benefits. Finally, it discusses the challenges to realize the full potential of long-acting sustained-release MNs in the clinic.

Natural mucilages are auspicious biodegradable polymeric materials. The aim of the present research work was to elucidate the characteristics of quince mucilage-based polymeric network for sustained delivery of metprolol tartrate and its toxicity evaluation. Mucilage was extracted by hot water extraction, and characterization of quince mucilage was accomplished by using Fourier transform infrared (FTIR) spectroscopy. Different batches of quince mucilage polymeric network were prepared by free radical polymerization by utilizing varying ratios of quince mucilage, acrylamide and crosslinker. Degree of swelling depends on concentration of mucilage, monomer and also on crosslinking density of polymeric network. FTIR illustrates proficient grafting, and morphological (scanning electron microscopy) analysis signified porous design. Hence, quince mucilage-based design was encouraging for sustained delivery of metprolol tartrate and acute toxicity evaluation proved that mucilage-based network was safe for oral drug delivery system.

In the current study, the combined anti-tumor efficacy of bioactive hydroxyapatite nano- particles (HA-NPs) loaded with altretamine (ALT) was evaluated. The well-known fact that HA has great biological compatibility was confirmed through the findings of the hemolytic experiments and a maximum IC50 value seen in the MTT testing. The preparation of HA-NPs was performed using the chemical precipitation process. An in vitro release investigation was conducted, and the results demonstrated the sustained drug release of the altretamine-loaded hydroxyapatite nanoparticles (ALT-HA-NPs). Studies using the JURKAT E6.1 cell lines MTT assay, and cell uptake, as well as in vivo pharmacokinetic tests using Wistar rats demonstrated that the ALT-HA-NPs were easily absorbed by the cells. A putative synergism between the action of the Ca2+ ions and the anticancer drug obtained from the carrier was indicated by the fact that the ALT-HA-NPs displayed cytotoxicity comparable to the free ALT at 1/10th of the ALT concentration. It has been suggested that a rise in intracellular Ca2+ ions causes cells to undergo apoptosis. Ehrlich’s ascites model in Balb/c mice showed comparable synergistic efficacy in a tumor regression trial. While the ALT-HA-NPs were able to shrink the tumor size by six times, the free ALT was only able to reduce the tumor volume by half.

Implantable drug-eluting devices that provide therapeutic cover over an extended period of time following a single administration have potential to improve the treatment of chronic conditions. These devices eliminate the requirement for regular and frequent drug administration, thus reducing the pill burden experienced by patients. Furthermore, the use of modern technologies, such as 3D printing, during implant development and manufacture renders this approach well-suited for the production of highly tuneable devices that can deliver treatment regimens which are personalised for the individual. The objective of this work was to formulate subcutaneous implants loaded with a model hydrophobic compound, olanzapine (OLZ) using robocasting - a 3D-printing technique. The formulated cylindrical implants were prepared from blends composed of OLZ mixed with either poly(caprolactone) (PCL) or a combination of PCL and poly(ethylene)glycol (PEG). Implants were characterised using scanning electron microscopy (SEM), thermal analysis, infrared spectroscopy, and X-ray diffraction and the crystallinity of OLZ in the formulated devices was confirmed. In vitro release studies demonstrated that all the formulations were capable of maintaining sustained drug release over a period of 200 days, with the maximum percentage drug release observed to be c.a. 60% in the same period.

Diabetes mellitus is a major healthcare challenge. Pramlintide, a peptide analogue of the hormone amylin, is currently used as an adjunct with insulin for patients who fail to achieve glycemic control with only insulin therapy. However, hypoglycemia is the dominant risk factor associated with such approaches and careful dosing of both drugs is needed. To mitigate this risk factor and compliance issues related to multiple dosing of different drugs, sustained delivery of Pramlintide from silica depot administered subcutaneously (SC) was investigated in a rat model. The pramlintide-silica microparticle hydrogel depot was formulated by spray drying of silica sol-gels. In vitro dissolution tests revealed an initial burst of pramlintide followed by controlled release due to the dissolution of the silica matrix. At higher dosing, pramlintide released from subcutaneously administered silica depot in rats showed a steady concentration of 500 pM in serum for 60 days. Released pramlintide retained its pharmacological activity in vivo, as evidenced by loss of weight. The biodegradable silica matrix offers a sustained release of pramlintide for at least two months in the rat model and shows potential for clinical applications.

Diabetes can be associated with profound visual loss due to several mechanisms. As the duration of diabetes and blood glucose levels increase, these changes become more severe. The proliferation of new blood vessels, vitreous hemorrhage, and tractional retinal detachments may ultimately result and can be devastating to visual function. New advances, including anti-vascular endothelial growth factor (VEGF) medications and innovative microsurgical instruments, have provided additional methods for the management of diabetic retinopathy in the clinic and in the operating room, leading to improved outcomes. Advances in earlier treatment of proliferative diabetic retinopathy, especially with anti-VEGF injections, allow for a reduction in severity, improved vision, and more controlled and successful surgery. Modern surgical techniques and instrumentation have also allowed for improved patient outcomes. Future research into sustained delivery and release of anti-VEGF, reducing the need for frequent in-office injections, may prove to be additionally beneficial. Over the last decade, anti-VEGF has become an increasingly common treatment modality for the management of proliferative diabetic retinopathy, vitreous hemorrhages, and tractional retinal detachments. Further research is needed to determine the ideal method of delivery and timing of the treatment.

Institutional mathematics education has long been traditional in its ways of being teacher-centric, a tradition which perhaps dates back to the Ancient Greece. Much like the society in those days, where there was a wary public feeling about the rigidness of the mathematical instruction in Pythagoras’ school, mathematics educators find themselves in a similar position in the common era of 2020. Unlike the Ancient Greece however, the battle is for the sustained delivery of a comprehensive mathematics education in the midst of the Covid-19 pandemic. It would be fair to say that mathematics departments across all levels of the education sector have been affected drastically;more so on instructors who favour the traditional “chalk and talk” method of instruction. In this article, we share several lessons learned in the delivery of mathematical instruction at undergraduate university level during the Covid-19 pandemic, drawing on our experience at Universiti Brunei Darussalam. These include specific methods for implementing online learning effectively, the pros and cons of such methods, and how we can use computer based tools to make learning more conducive. We highly think that these implementations are beneficial to be adapted by mathematics departments anywhere as a means of adapting to the new realities post Covid-19. © 2022, Institute of Technology PETRONAS Sdn Bhd.

Polymeric vehicles are versatile tools for therapeutic gene delivery. Many polymers—when assembled with nucleic acids into nanoparticles or polyplexes—can protect the cargo from degradation and clearance in vivo, and facilitate its transport into intracellular compartments. Design options in polymer synthesis yield a comprehensive range of molecules and resulting vehicle formulations. These properties can be manipulated to achieve stronger association with nucleic acid cargo and cells, improved endosomal escape, or sustained delivery depending on the application. Here, we describe current approaches for polymer use and related strategies for gene delivery in preclinical and clinical applications. Polymer vehicles delivering genetic material have already achieved significant therapeutic endpoints in vitro and in animal models. From our perspective, with preclincal assays that better mimic the in vivo environment, improved strategies for target specificity, and scalable techniques for polymer synthesis, the impact of this therapeutic approach will continue to expand.

Cell microencapsulation within biocompatible polymers is an established technology for immobilizing living cells that secrete therapeutic products. These can be transplanted into a desired site in the body for the controlled and continuous delivery of the therapeutic molecules. One of the most important properties of the material that makes up the microcapsule is its oxygen penetrability, which is critical for the cells’ survival. Oxygen reaches the cells inside the microcapsules via a diffusion process. The diffusion coefficient for the microcapsules’ gel material is commonly measured using bulk techniques, where the gel in a chamber is first flushed with nitrogen and the subsequent rate of oxygen diffusion back into it is measured by an oxygen electrode placed in the chamber. This technique does not address possible heterogeneities between microcapsules, and also cannot reveal O2 heterogeneity inside the microcapsule resulting from the living cells’ activity. Here we develop and demonstrate a proof of principle for a new approach to measuring and imaging the partial pressure of oxygen (pO2) inside a single microcapsule by means of high-resolution and high-sensitivity electron spin resonance (ESR). The proposed methodology makes use of biocompatible paramagnetic microparticulates intercalated inside the microcapsule during its preparation. The new ESR approach was used to measure the O2 diffusion properties of two types of gel materials (alginate and extracellular matrix – ECM), as well as to map a 3D image of the oxygen inside single microcapsules with living cells. Statement of Significance The technology of cell microencapsulation offers major advantages in the sustained delivery of therapeutic agents used for the treatment of various diseases ranging from diabetes to cancer. Despite the great advances made in this field, it still faces substantial challenges, preventing it from reaching the clinical practice. One of the primary challenges in developing cell microencapsulation systems is providing the cells with adequate supply of oxygen in the long term. Nevertheless, there is still no methodology good enough for measuring O2 distribution inside the microcapsule with sufficient accuracy and spatial resolution without affecting the microcapsule and/or the cells’ activity in it. In the present work, we introduce a novel magnetic resonance technique to address O2 availability within cell-entrapping microcapsules. For the first time O2 distribution can be accurately measured and imaged within a single microcapsule. This new technique may be an efficient tool in the development of more optimal microencapsulation systems in the future, thus bringing this promising field closer to clinical application.

Supramolecular hydrogels have great potential as biomaterials for sustained delivery of therapeutics. While peptide-based supramolecular hydrogels have been developed that show promise for drug delivery applications, the high cost of production has limited their widespread adoption. Low molecular weight (LMW) supramolecular hydrogels are emerging as attractive and inexpensive alternatives to peptide-based hydrogels. We recently reported novel cationic fluorenylmethyloxycarbonyl-modified phenylalanine (Fmoc-Phe) hydrogels for localized and sustained in vivo release of an anti-inflammatory agent for functional pain remediation. In an effort to further elucidate design principles to optimize these materials for delivery of a variety of molecular agents, we herein report a systematic examination of electrostatic effects on the release of cargo molecules from Fmoc-Phe derived hydrogels. Specifically, we interrogate the release of cationic, anionic, and neutral cargo molecules from a series of cationic and anionic Fmoc-Phe derived hydrogels. We observed that cargo was readily released from the hydrogels except when the cargo and hydrogel network had complementary charges, in which case the cargo was highly retained in the network. These results demonstrate that the electrostatic characteristics of both the hydrogel network and the specific cargo are critical design parameters in the formulation of LMW supramolecular hydrogel systems in the development of next-generation materials for drug delivery applications.

Present investigation reports a straight forward method for synthesis of graphene oxide (GO) followed by fabrication of graphene oxide microsphere (GMS) using water in oil (w/o) emulsificat...

The chemically oxidized gum arabic was prepared and used as a naturally derived nontoxic and pH-responsive cross-linker to develop smart polyvinyl alcohol (PVA)-based hydrogels for the first time. The formulated hydrogels exhibited high mechanical properties, good porosity, and pH sensitivity, which facilitated their application as promising biomaterials for sustained delivery of folic acid. Further, the synthesized cross-linked PVA hydrogels displayed no cytotoxicity toward the human embryonic kidney cell line and exhibited higher blood compatibility. The hydrolytic degradation study confirmed their biodegradable nature. While the sustained delivery along with photoprotective properties of these hydrogels confirmed their multifunctional characteristics, these results suggest that these hydrogels may act as an efficient photoprotective material and find their application in the field of drug delivery.

Inorganic cells bearing calcium silicate membranes were prepared and resembled closed chemical gardens. It was demonstrated that these inorganic cells can successfully be loaded with natural products, proteins and plasmid DNA, and their cargo can be released in a controlled manner. These cells demonstrated the ability of chemical gardens to act as platforms for the sustained delivery of biomolecules and are expected to introduce chemical gardens in the field of biosciences.

Objective: The present research work is aimed at the development of an in situ gel polymer composite to provide local and sustained delivery of therapeutic agents in the vaginal cavity. Administration of medicated gel into a vaginal cavity is very complicated, inconvenient and needs expert assistance. There is a chance of expulsion of liquid formulation from site of application, leads to poor therapeutic efficacy. The effective drug delivery system for the vaginal cavity should be of liquid for application and gel to reside in the cavity. Methods: In situ gel composed of chitosan (0.8%) cross-linked with β-glycerol phosphate (15%) and glutaraldehyde treated guar gum (0.2%) was developed. Gel was characterized for in situ gelling properties. In vitro drug release pattern of the gel was tested on a nutrient agar medium containing attenuated E. coli and B. Subtilis. In vitro diffusion pattern of gel was tested using KC-diffusion cell with Simulated Vaginal Fluid (SVF) (pH 4.2) as the diffusion medium. Results: In situ gel exhibited sharpest sol-gel transition at 35±2°C, at pH 5.4 in 62±1.31sec. The viscosity of polymer composite is 51.25±3.68 CPs at 20±2°C and 328.56±4.16 CPs at 35±2°C. The gelation time of gel was found to be decreasing as the concentration of cross-linking agent β-GP increased. Formulations exhibited a shear thinning property. Drug release from this polymeric composite was found to be highly linear and follows non-fickian diffusion mechanism. Conclusion: This advanced thermosensitive in situ gel is convenient to apply and reside in the vaginal cavity for a prolonged period of time. The gel is mucoadhesive, biodegradable and suitable for controlled drug delivery in the cavity.

Nanoscale science and nanotechnology are expected to bring about revolutionary advances in the agrochemical industry. Smart delivery of micronutrients enabling sustained release is one such innovative approach to combat the poor nutrient uptake efficiency of conventional micronutrient sources. Herein, we report a bottom-up surface fabrication strategy to modify nanosized zinc oxide (ZnO NPs) surfaces at an atomic scale for sustained release of Zn micronutrients. A large sized environmentally relevant macromolecule humic acid (HA) and a comparatively smaller biologically pertinent citrate ligand were used to functionalize ZnO NPs (30 nm), and the resultant nanohybrids were characterized using electron microscopy, diffraction, and spectroscopic techniques. Functionalization with citrate ligand turns the NP smaller than its original size. The resultant modification in the dissolution characteristics of ZnO NPs leads to sustained release of Zn over a broad pH range. Functionalization with HA causes minimum al...

Background and aim: We have synthesized a novel lactone-stabilized camptothecin (CPT) analog named CZ48 and demonstrated its potent anticancer effects via bioconversion to the active CPT in earlier studies. Herein, we aimed to develop, optimize and characterize CZ48 nanosuspensions, for a sustained delivery of this drug in humans with an intravenous (i.v.) administration. Methods and materials: A three-factor, five-level central composite design (CCD) was employed to establish the impacts of the critical influencing factors (concentrations (wt%) of CZ48, polysorbate 80 (Tween-80), and Pluronic® F-108 (F-108)) on the responses (particle size and zeta potential). Based on the quantitative influencing factor-response relationships, two optimized CZ48 nanosuspensions of 197.22 ± 7.12 nm (NS-S) and 589.35 ± 23.27 nm (NS-L) were developed with the zeta potential values of -26.5 mV and -27.9 mV, respectively. Results: CZ48 released from the nanosuspensions in a sustained manner in contrast to the rapid release from cosolvent in both PBS and human plasma. Moreover, NS-S exhibited more favored pharmacokinetic properties than NS-L, with a 31-fold prolonged elimination half-life of CPT, and a 2.4-fold enhanced CPT exposure over cosolvent. In efficacy study, NS-S exhibited significant tumor suppression and an improved survival rate with a higher tolerable dose, compared to CZ48 cosolvent. Conclusion: We have successfully developed CZ48 nanosuspensions with significantly favorable pharmacokinetics and improved efficacy using CCD approach. The formulation offers potential merits as a preferred candidate for clinical trials with the prolonged CPT exposure, which is known to correlate with the clinical efficacy.

In this article, we review new and emerging drug delivery methods used in the treatment of glaucoma. Several methods for sustained delivery of glaucoma medications have shown promise recently. Drug-eluting punctal plugs, contact lenses, and fornix-based silicone rings as well as subconjunctival and intracameral injections or implants are either in development or clinical trials. Thus far, those studied have demonstrated significant intraocular pressure (IOP) lowering ability with favorable safety profiles. However, long-term clinical safety data and comparative trials with existing therapies have been limited. Patient adherence with medication regimens remains a major obstacle in preventing glaucoma progression. Emerging patient-independent platforms that can deliver IOP lowering therapeutics hold promise for enhancement of adherence to treatments while remaining safe and effective. Each of these systems has their own unique advantages and disadvantages. It is still unclear where each of these products will fit into individual patient and practitioner treatment algorithms.

Drug delivery through the skin offers many advantages such as avoidance of hepatic first-pass metabolism, maintenance of steady plasma concentration, safety, and compliance over oral or parenteral pathways. However, the biggest challenge for transdermal delivery is that only a limited number of potent drugs with ideal physicochemical properties can passively diffuse and intercellularly permeate through skin barriers and achieve therapeutic concentration by this route. Significant efforts have been made toward the development of approaches to enhance transdermal permeation of the drugs. Among them, microneedles represent one of the microscale physical enhancement methods that greatly expand the spectrum of drugs for transdermal and intradermal delivery. Microneedles typically measure 0.1–1 mm in length. In this review, microneedle materials, fabrication routes, characterization techniques, and applications for transdermal delivery are discussed. A variety of materials such as silicon, stainless steel, and polymers have been used to fabricate solid, coated, hollow, or dissolvable microneedles. Their implications for transdermal drug delivery have been discussed extensively. However, there remain challenges with sustained delivery, efficacy, cost-effective fabrication, and large-scale manufacturing. This review discusses different modes of characterization and the gaps in manufacturing technologies associated with microneedles. This review also discusses their potential impact on drug delivery, vaccine delivery, disease diagnostic, and cosmetics applications.

Many biologics have a short plasma half-life, and their conjugation to polyethylene glycol (PEG) is commonly used to solve this problem. Unfortunately, PEG is immunogenic and forms vacuoles, and improvement in PEGylated drugs' half-life is at an asymptote. Here, we developed a PEG-like, non-immunogenic, and injectable conjugate technology for sustained delivery of biologics. An optimal poly[oligo(ethylene glycol) methyl ether methacrylate] (POEGMA) depot of exendin, a peptide drug used in the clinic in treating type 2 diabetes, outperformed PEG, non-depot-forming POEGMA, and a clinical sustained-release exendin-4 formulation in efficacy and pharmacokinetics. Notably, POEGMA was non-immunoreactive, while PEG induced a persistent anti-PEG immune response, leading to its subsequent doses' early clearance and loss of efficacy. POEGMA did not induce vacuolization. Solving these problems of PEG and improving upon its half-life benefits by creating injectable POEGMA conjugates that form a drug depot under the skin and provide sustained efficacy breathe new life into an established and valuable drug delivery technology that is facing an impasse.

Designing hydrogels for controlled drug delivery remains a big challenge. We developed a calcium polyphosphate hydrogel (CPP) as matrix for delivery of vancomycin (VCM) and erythromycin (EM) by unique ionic binding and physical wrapping. In this continuing study, we investigated if gel discs prepared by mechanical compaction (at 3000 psi pressure, C-discs) is superior to that of discs prepared by regular manual compaction (M-discs) for the release of VCM and EM (10 wt.%). Data demonstrated a significant reduction of burst release of VCM and EM in C-discs (1.8% and 5%, respectively) as compared to that from M-discs within 72 hr (55% and 60%, respectively, p

Despite their high efficacy and safety, long-acting contraceptive methods are underutilized among women in some settings because they usually require injection or implantation by healthcare personnel. Here, we report a self-administrable microneedle (MN) patch for the rapid administration of a sustained-release contraceptive hormone delivery system into the skin that increases the simplicity and reliability of the MN delivery. We developed an immediate microneedle detachment system using a porous patch backing that has sufficient strength during MN insertion into skin under compression, but enables immediate detachment (1 s) of the MNs due to fracture at the MN - backing interface upon patch removal under tension from the skin surface. After patch application, the removed patch produced no biohazardous sharps waste, and was designed to achieve long-acting contraception by formulating poly(lactic-co-glycolic acid) MNs to slowly release the contraceptive hormone levonorgestrel for up to 1 month. Our combined strategy using immediate MN detachment in the skin and sustained drug delivery from the MNs could facilitate greater access to long-acting contraception by providing a simple and convenient option for self-administered, long-acting contraception.

With the rapid development of the biopharmaceutical industry, an increasing number of new therapeutic protein products (TPPs) have been approved by the FDA and many others are under pre-clinical and clinical evaluation. A major limitation of biopharmaceuticals is their limited half-life when administered systemically. A one-time, implantable, sustained protein delivery device would be advantageous in order to improve the quality of life of patients. Hot melt extrusion (HME) is a mature technology that has been extensively used for a broad spectrum of applications in the polymer and pharmaceutical industry and has achieved success as evidenced by a variety of FDA-approved commercial products. These commercial products are mostly for sustained delivery of small molecule therapeutics, leaving a significant gap for HME formulation of therapeutic proteins. With the increasing need of sustained TPP delivery, HME shows promise as a downstream processing method due to its high efficiency and economic value. Several challenges remain for the application of HME in protein delivery. Progress of HME for protein delivery, challenges encountered, and potential solutions will be detailed in this review article. This article is categorized under: Implantable Materials and Surgical Technologies > Nanomaterials and Implants Biology-Inspired Nanomaterials > Protein and Virus-Based Structures.

The prevalence of many ocular diseases increases with age, and as average global life expectancy increases the burden of age-related and diabetes-related eye diseases follows. Current drug-delivery technologies for ocular diseases rely on two principal modalities: topical drops and intravitreal injections. Topical drops primarily treat front-of-eye disease as complex anatomical and physiological barriers often limit the success of therapies targeting the back of the eye, especially with respect to protein delivery. Intravitreal injections, on the other hand, deliver protein therapeutics directly to the vitreous. However, problems including the large size, poor permeation, and susceptibility of proteins and peptides to degradation leads to the therapeutic benefits of these strategies lasting only several weeks. Patient compliance with frequent drug administration remains a challenge for effective treatment of ocular disease, prompting next-generation drug-delivery systems to explore ways to deliver therapeutics for extended periods of time. First-generation non-biodegradable reservoir-based systems were robust, contained large reservoirs delivering small molecules, and could be removed from the eye if adverse effects occurred. Future approaches can improve these technologies by developing devices that deliver protein and peptides, degrade upon drug depletion, and decrease or eliminate complications associated with surgical procedures. This chapter will highlight recent advances in ocular drug-delivery devices in preclinical stages, clinical trials, and those approved by the United States Food and Drug Administration. We will also describe ocular diseases of interest, the current state of proteins and peptides for ocular therapeutics, and considerations for sustained delivery of protein and biologics.

The transdermal route of drug administration is the most widely used route for systemic administration of drugs due to the convenience and noninvasiveness it provides. Skin is one of the largest organs offering multiple sites for drug delivery and acting as “reservoir” for sustained delivery of drugs. However, the penetration of drugs through skin is hindered due to stratum corneum, which acts as an efficient barrier. In order to overcome this barrier, nanocarriers (liposomes, nanoparticles, ethosomes, dendrimers, etc.) have emerged as an efficient tool for delivering a range of drugs through stratum corneum. In this chapter, various nanocarriers for transdermal delivery, their applications, commercial formulations, safety, and toxicity are described.

The increase in life expectancy is favoring the prevalence of musculoskeletal diseases that compromise the quality of life of millions of people all over the world. Moreover, some life styles promote the early apparition of degenerative diseases. The unmet clinical demand of tissue regeneration prompts the searching of novel strategies. Cyclodextrins (CDs) have an outstanding track record as versatile tools for drug formulation. Although still less explored, CDs are being found useful for a variety of purposes in the design of advanced scaffolds for regenerative medicine. CDs can simultaneously host therapeutic agents and structural components of the scaffolds serving as reversible tie-junctions. Versatile 2D nanostructured systems can be obtained by means of electrospinning. Soft 3D supramolecular structures can be prepared as syringeable materials to be administered using minimally invasive techniques, with the additional advantage of ensuring a full filling of the gap in the damage tissue. Additionally, CDs have recently been demonstrated suitable to prepare patient-personalized scaffolds by means of 3D printing, opening novel approaches for scaffold design using additive manufacture techniques. 2D and 3D CD-based scaffolds have shown advanced performances for various tissues regeneration, including bone and cartilage, combining cell growth support and sustained delivery of active substances, growth factors and even viral vectors for improved tissue repair and angiogenesis. This talk aims to provide an overview of the state-of-the-art of the use of CDs in bone regeneration. Although most information still refers to in vitro and preclinical studies, recent progresses in the field point out CDs as key components of improved scaffolds.

Background Majorly, the reason for the permanent loss of vision is glaucoma. But the currently available common treatment methodologies such as eye drops have various disadvantages like patient incompliance due to repeated administration and poor (1–5%) bioavailability leading to poor efficiency. The objective of this research was to formulate Eudragit-based nanoparticles of levobunolol incorporated into a contact lens to obtain sustained ocular delivery of levobunolol at the therapeutics level. Eudragit nanoparticles of levobunolol were formulated by nanoprecipitation methodology utilizing different ratios of Eudragit S100 and polyvinyl alcohol. The prepared nanoparticles were evaluated and optimized by efficiency of entrapment, particle size, morphology of surface and zeta potential. The optimized nanoparticles were then entrapped into the matrix of the contact lens by the soaking method which were then characterized and compared for optical clarity study, equilibrium swelling study, shelf life and in vitro drug release in simulated tear fluid followed by ex vivo transcorneal permeation study. Results Formulation F3 was obtained as optimized nanoparticle formulation with 102.61 nm ± 3.92 of particle size, − 22.2 mV ± 2.76 of zeta potential and 86.995% ± 1.902 of efficiency of entrapment. The equilibrium swelling index and transmittance of nanoparticle incorporated into contact lenses showed better results when compared to drug solution-loaded lenses. In vitro release indicated more sustained drug profiles (84.33% ± 0.34 of drug release over a period of 12 days) as compared to drug solution-loaded lenses (89.282% ± 0.900 of drug release over a period of 3 days). Ex vivo transcorneal permeation studies showed more permeation (6.75% ± 0.170) through contact lenses as compared to marketed eye drops (3.03% ± 0.088). Conclusion This research demonstrates the remarkable results of drug-laden contact lenses to serve as a great medium for the continued delivery of ocular drugs without affecting the physical and optical characteristics of the lens content.

A self-healing microcapsule loaded with leukemia-associated antigens, epitope peptides, and PD-1 antibody demonstrates sustained delivery of a leukemia vaccine.

Since 1998, educators at Wheeling Jesuit University’s Challenger Learning Center and Center for Educational Technologies have created realistic live simulations of science and medical emergencies in which students act as astronauts, scientists or doctors to solve STEM problems such as diagnosing diseases, stopping epidemics, picking a safe spacecraft landing spot, and rescuing stranded astronauts. These 90 to 120-minute simulations, e-Missions, are video-conferenced into classrooms, with companion websites providing pre-mission preparation, supplemental resources and teacher tutorials. e-Missions have been used more than 11,000 times at schools in 50 states and 22 nations. More than 310,000 elementary, middle and high school students have role-played STEM experts, and 10,000 teachers were trained to use technology and problem-based learning. Shorter live missions, e-Labs, were created to demonstrate science topics in 3–9 grade classrooms, and e-Labs Jr do the same for K-3. The simulations and e-Labs are developed with funding from agencies, foundations and corporations, and are maintained through payments by schools of $400 to $550 for each e-Mission, and $200 for e-Labs, often year after year as culminating events for relevant curricula. More than $5 million dollars have been earned over the last 20 years, supporting the sustained delivery of these innovative STEM experiences, and software and hardware updates. Evaluations have identified positive changes in e-Mission student attitudes and perceptions toward science and science careers.

The development of microneedles (MNs) assisted drug delivery technologies have been highly active for more than two decades. The minimally invasive and self-administered MN technology bypasses many challenges associated with injectable drug delivery systems, by delivering the therapeutic materials directly into the dermal and ocular space and allowing the release of the active ingredient in a sustained or controlled manner. Different types of MNs (biodegradable solid/dissolving MNs and nanoparticle loaded/coated polymeric MNs or delivery by hollow MNs) have been envisioned for long-acting sustained delivery of therapeutic payloads, with the aim of reducing the side effects and administration frequency to improve the patient compliance. In this review, we covered the different types of MNs loaded with different nano/biotherapeutics for long-acting delivery for a wide range of potential clinical applications. We also outlined the future development scenario of such long-acting MN delivery systems for different disease conditions to achieve improved clinical benefit. Finally, we discussed the challenges lie ahead to realize the full potential of sustained-release long-acting MNs in the clinic.

The Oral route of administration forms the heartwood of the ever-growing tree of drug delivery technology. It is one of the most preferred dosage forms among patients and controlled release community. Despite the high patient compliance, the deliveries of anti-cancerous drugs, vaccines, proteins, etc. via the oral route are limited and have recorded a very low bioavailability. The oral administration must overcome the physiological barriers (low solubility, permeation and early degradation) to achieve efficient and sustained delivery. This review aims at highlighting the conventional and modern-age strategies that address some of these physiological barriers. The modern age designs include the 3D printed devices and formulations. The superiority of 3D dosage forms over conventional cargos is summarized with a focus on long-acting designs. The innovations in Pharmaceutical organizations (Lyndra, Assertio and Intec) that have taken giant steps towards commercialization of long-acting vehicles are discussed. The recent advancements made in the arena of oral peptide delivery are also highlighted. The review represents a comprehensive journey from Nano-formulations to micro-fabricated oral implants aiming at specific patient-centric designs.