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Over several decades, natural polysaccharides (PSs) have been actively exploited for their wide bioactivities. So far, many PS-related reviews have been published; however, none focused on the delivery of bioactive PSs as therapeutic molecules. Herein, we summarized and discussed general pharmacokinetic properties of PSs and drug delivery systems (DDSs) developed for them, together with the challenges and prospects. Overall, most bioactive PSs suffer from undesirable pharmacokinetic attributes, which negatively affect their efficacy and clinical use. Various DDSs therefore have been being utilized to improve the drug-like properties and curative efficacy of bioactive PSs by means of improving oral absorption, controlling the release, enhancing the in vivo retention ability, targeting the delivery, exerting synergistic effects, and so on. Specifically, nano-sized insoluble DDSs were mainly applied to improve the oral absorption and target delivery of PSs, among which liposome was especially suitable for immunoregulatory and/or anti-ischemic PSs due to its synergistic effects in immunoregulation and biomembrane repair. Chemical conjugation of PSs was mainly utilized to improve their oral absorption and/or prolong their blood residence. With formulation flexibility, in situ forming systems alone or in combination with drug conjugation could be used to achieve day(s)- or month(s)-long sustained delivery of PSs per dosing.

The demand of contraception and fertility control of animals is huge in livestock field and pet market. In this study, we suggest a formulation made up of an injectable and biodegradable thermogel for sustained delivery of levonorgestrel (LNG), a hormonal contraceptive, to realize the long-acting animal contraception. A thermogelling poly(lactic acid-co-glycolic acid)-poly(ethylene glycol)-poly(lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) triblock copolymer was synthesized in a one-pot reaction. The micelles formed by the amphiphilic polymer carriers in water could serve as a reservoir for the solubilization of hydrophobic LNG molecules. The concentrated polymer aqueous solution exhibited a reversible sol-gel transition upon heating, and the incorporation of various amounts of LNG was found not to affect the thermogelation of the polymer/water system. In vitro release profiles showed that the entrapped LNG was sustainedly released from the thermogel matrix and the initial drug-loading amounts had a significant influence on the release kinetics of LNG. In vivo pharmacokinetic studies demonstrated that the use of PLGA-PEG-PLGA thermogel markedly extended the release of LNG after subcutaneous injection into SD rats. Consequently, this study revealed that the injectable PLGA-PEG-PLGA thermogel was a promising candidate for sustained delivery of LNG, and provided an attractive option for long-term contraception and fertility control of animals by a way of facile fabrication, easy administration and low expense.

There is a clear and urgent clinical need to develop soft tissue fillers that outperform the materials currently used for adipose tissue reconstruction. Recently, extensive research has been performed within this field of adipose tissue engineering as the commercially available products and the currently existing techniques are concomitant with several disadvantages. Commercial products are highly expensive and associated with an imposing need for repeated injections. Lipofilling or free fat transfer has an unpredictable outcome with respect to cell survival and potential resorption of the fat grafts. Therefore, researchers are predominantly investigating two challenging adipose tissue engineering strategies: in situ injectable materials and porous 3D printed scaffolds. The present work provides an overview of current research encompassing synthetic, biopolymer-based and extracellular matrix-derived materials with a clear focus on emerging fabrication technologies and developments realized throughout the last decade. Moreover, clinical relevance of the most promising materials will be discussed, together with potential concerns associated with their application in the clinic.

The aim of present investigation was to characterize carboxymethyl tamarind gum (CMTG) based interpenetrating networks (IPNs) of aceclofenac for site specific sustained delivery. The drug loaded IPNs were prepared by using chitosan and CMTG as polymers and gluteraldehyde as crosslinking agent. The IPNs were characterized by Attenuated total reflectance- Fourier transform infrared (ATR-FTIR) spectroscopy, thermal analysis, X-ray powder diffraction and solid state 13C-nuclear magnetic resonance spectroscopy. The prepared IPNs were evaluated for the drug entrapment efficiency and equilibrium swelling. The drug release from IPNs was studied in 0.1NHCl for 2h followed by phosphate buffer pH 6.8 for further 10h and compared with commercial tablet. The results of ATR-FTIR and thermal analysis for blank IPNs indicated intercalation of polymeric chains of crosslinked CMTG and chitosan. The results of solid state characterization revealed that the aceclofenac is compatible with IPNs. Entrapment efficiency of IPNs was found to be increased with increase in crosslinker concentration as well as amount of CMTG. The equilibrium swelling study indicated pH dependent swelling of IPNs. The drug release by IPNs showed sustained release of aceclofenac upto 12h while commercial formulation showed fast release within 8h. From the results, it can be concluded that the IPNs of CMTG and chitosan has potential in development of site specific sustained drug delivery.

Talazoparib, a potent PARP inhibitor, has shown promising clinical and pre-clinical activity by inducing synthetic lethality in cancers with germline Brca1/2 mutations. Conventional oral delivery of Talazoparib is associated with significant off-target effects, therefore we sought to develop new delivery systems in the form of an implant loaded with Talazoparib for localized, slow and sustained release of the drug at the tumor site in Brca1-deficient breast cancer. Poly(lactic-co-glycolic acid) (PLGA) implants (0.8 mm diameter) loaded with subclinical dose (25 or 50 µg) Talazoparib were fabricated and characterized. In vitro studies with Brca1-deficient W780 and W0069 breast cancer cells were conducted to test sensitivity to PARP inhibition. The in vivo therapeutic efficacy of Talazoparib implants was assessed following a one-time intratumoral injection in Brca1Co/Co;MMTV-Cre;p53+/- mice and compared to drug-free implants and oral gavage. Immunohistochemistry studies were performed on tumor sections using PCNA and γ-H2AX staining. Sustained release of Talazoparib was observed over 28 days in vitro. Mice treated with Talazoparib implants showed statistically significant tumor growth inhibition compared to those receiving drug-free implants or free Talazoparib orally. Talazoparib implants were well-tolerated at both drug doses and resulted in less weight loss than oral gavage. PARP inhibition in mice treated with Talazoparib implants significantly increased double-stranded DNA damage and decreased tumor cell proliferation as shown by PCNA and γ-H2AX staining as compared to controls. These results demonstrate that localized and sustained delivery of Talazoparib via implants has potential to provide superior treatment outcomes at sub-clinical doses with minimal toxicity in patients with BRCA1 deficient tumors.

Age-related macular degeneration (AMD) is one of the leading causes of irreversible blindness in the developed world. Antivascular endothelial growth factor therapy has transformed the management and outcome of neovascular AMD (nAMD), although the need for repeated intravitreal injections—even lifelong—and the related complications, high drug costs, frequent clinic visits and repeated imaging have resulted in an enormous burden both to healthcare systems and patients. The application of gene therapy approaches for sustained delivery of a range of antiangiogenic proteins has the promise of helping to address these aforementioned challenges. A number of early phase clinical trials of gene therapy in nAMD have provided encouraging results, with many more ongoing or anticipated. There remain significant areas of controversy, including regarding the optimal treatment targets, routes of administration and potential safety concerns. In this review we aim to provide an update of the current status of gene therapy for nAMD and briefly discuss future prospects.

Dry eye disease (DED) is a common multifactorial disease linked to the tears/ocular surface leading to eye discomfort, ocular surface damage, and visual disturbance. Antiinflammatory agents (steroids and cyclosporine A), hormonal therapy, antibiotics, nerve growth factors, essential fatty acids are used as treatment options of DED. Current therapies attempt to reduce the ocular discomfort by producing lubrication and stimulating gland/nerve(s) associated with tear production, without providing a permanent cure for dry eye. Nanocarrier systems show a great promise to revolutionize drug delivery in DED, offering many advantages such as site specific and sustained delivery of therapeutic agents. This review presents an overview, pathophysiology, prevalence and etiology of DED, with an emphasis on preclinical and clinical studies involving the use of nanocarrier systems in treating DED. Lay Summary: Lay Summary: Dry eye disease (DED) is a multifactorial disease associated with tear deficiency or excessive tear evaporation. There are several review articles that summarize DED, disease symptoms, causes and treatment approaches. Nanocarrier systems show a great promise to revolutionize drug delivery in DED, offering many advantages such as site specific and sustained delivery of therapeutic agents. Very few review articles summarize the findings on the use of nanotherapeutics in DED. In this review, we have exclusively discussed the preclinical and clinical studies of nanotherapeutics in DED therapy. This information will be attractive to both academic and pharmaceutical industry researchers working in DED therapeutics.

We describe the preparation of injectable polymeric paste (IPP) formulations for local and sustained release of drugs. Furthermore, we include the characterization and possible applications of such pastes. Particular attention is paid to characteristics relevant to the successful clinical formulation development, such as viscosity, injectability, degradation, drug release, sterilization, stability performance and pharmacokinetics. Paste injectability was characterized using measured viscosity and the Hagen-Poiseuille equation to determine injection forces. Drug degradation, release and formulation stability experiments were performed in vitro and drug levels were quantified using HPLC-UV methods. Pharmacokinetic evaluation of sustained-release lidocaine IPPs used five groups of six rats receiving increasing doses subcutaneously. An anti-cancer formulation was evaluated in a subcutaneous tumor xenograft mouse model. The viscosity and injectability of IPPs could be controlled by changing the polymeric composition. IPPs demonstrated good long-term stability and tunable drug-release with low systemic exposure in vivo in rats. Preliminary data in a subcutaneous tumor model points to a sustained anticancer effect. These IPPs are tunable platforms for local and sustained delivery of drugs and have potential for further clinical development to treat a number of diseases.

As an emerging drug carrier, hydrogels have been widely used for tumor drug delivery. A hydrogel drug carrier can cause less severe side effects than systemic chemotherapy and can achieve sustained delivery of a drug at tumor sites. In addition, hydrogels have excellent biocompatibility and biodegradability and lower toxicity than nanoparticle carriers. Smart hydrogels can respond to stimuli in the environment (e.g., heat, pH, light, and ultrasound), enabling in situ gelation and controlled drug release, which greatly enhance the convenience and efficiency of drug delivery. Here, we summarize the different sizes of hydrogels used for cancer treatment and their related delivery routes, discuss the design strategies for stimuli-responsive hydrogels, and review the research concerning smart hydrogels reported in the past few years.

OBJECTIVES: The main objective of the present review is to explore and examine the effectiveness of currently developed novel techniques to resolve the issues which are associated with the herbal constituents/extract. METHODS: A systematic thorough search and collection of reviewed information from Science direct, PubMed and Google Scholar databases based on various sets of key phrases have been performed. All the findings from these data have been studied and briefed based on their relevant and irrelevant information. RESULT: Herbal drugs are gaining more popularity in the modern world due to their applications in curing various ailments with minimum toxic effects, side effect or adverse effect. However, various challenges exist with herbal extracts/plant actives such as poor solubility (water/lipid), poor permeation, lack of targeting specificity, instability in highly acidic pH, and liver metabolism, etc. Nowadays with the expansion in the technology, novel drug delivery system provides avenues and newer opportunity towards the delivery of herbal drugs with improved physical chemical properties, pharmacokinetic and pharmacodynamic. Developing nano-strategies like Polymeric nanoparticles, Liposomes, Niosomes, Microspheres, Phytosomes, Nanoemulsion and Self Nano Emulsifying Drug Delivery System, etc. imparts benefits for delivery of phyto formulation and herbal bioactives. Nano formulation of phytoconstituents/ herbal extract could lead to enhancement of aqueous solubility, dissolution, bioavailability, stability, reduce toxicity, permeation, sustained delivery, protection from enzymatic degradation, etc. CONCLUSION: Based on the above findings, the conclusion can be drawn that the nano sized novel drug delivery systems of herbal and herbal bioactives have a potential future for upgrading the pharmacological action and defeating or overcoming the issues related with these constituents. The aims of the present review was to summarize and critically analyze the recent development of nano sized strategies for promising phytochemicals delivery systems along with their therapeutic applications supported by experimental evidence and discussing the opportunities for further aspects. GRAPHICAL ABSTRACT: [Image: see text]

Sustained delivery of programs to improve the use of medicines and medical tests in primary care is a worthy objective. However, in order to be successful and to deliver interventions at scale, some prerequisites are needed. Programs should take account of the local culture and health system and have a clear understanding of the drivers for change when adapting or designing interventions. Being realistic about what the capacity of the implementation agency to influence change and/or control the environment ensures that resources are efficiently deployed. Similarly being absolutely clear about the behavior that one is trying to influence and the barriers and enablers for change will assist in designing effective programs and in guiding their evaluation. Investing in workforce, partnerships and strong evaluation will set implementation agencies up for long-term impact.

Tendon injuries are more common, and due to the lack of adequate growth factors, the healing capacity of the injured tendon is limited. The objective of this study is to evaluate the effectiveness of Nanoparticle-coated sutures carrying growth factors on accelerating tendon repair. We found that nanoparticles can adhere uniformly to the surface of the suture modified with polydopamine. After stitching, the nanoparticles remain on the surface of the suture, and its loaded proteins can spread in the tendon tissues. After treatment, in the chicken flexor tendon healing model and the rat Achilles healing model, the ultimate strengths of repaired tendons treated with bFGF and VEGFA-releasing sutures was significantly greater than the tendons repaired with control sutures at multiple time-points. At 6 weeks, adhesion scores in the bFGF and VEGFA-releasing suture group were significantly smaller than those of the control suture group. Tendon gliding excursions were significantly greater in the bFGF and VEGFA-releasing suture group than in the unmodified control sutures. Work of digital flexion was significantly decreased in the bFGF and VEGFA-releasing suture group than in the control group. In a word, we developed a novel platform for local and sustained delivery of growth factors based on the Nanoparticle-coated sutures, which can effectively deliver growth factors to tissues and control the release of growth factors. Dual growth factors loaded Nanoparticle-coated sutures can significantly promote tendon healing. This growth factors delivery system is an attractive therapeutic tool to repair injured tendons.

Plant-derived starches are vegetable polysaccharides occurring in cereals, seeds, corms, tubers, rhizomes, and root vegetables of various plants. These are recognized as biopolymers with diverse biomedical applications due to availability from nature, cost-effectiveness, biodegradability, and biocompatibility. During past few decades, a huge number of starches from different plant parts are being explored and expansively exploited as versatile pharmaceutical excipients like suspending agents, emulsifiers, diluents, disintegrating agents, binding agents, film-forming agents, matrix-forming agents, release retardants, and mucoadhesive excipients, in a variety of pharmaceutical dosage forms. Recent years, plant-derived starches have been used as polymeric blendings with sodium alginate for designing ionotropically gelled particulates (i.e., beads, microparticles) for the use in sustained drug releasing applications. The incorporation of these plant-derived starches within ionotropically gelled alginate matrix in the development of various alginate–plant-derived starches-based particulates minimize some potential limitations of ionotropically gelled alginate particles as drug carriers like lower drug entrapment, poor mechanical properties, and premature drug release behavior within short duration. The present chapter provides a discussion on various alginate–plant-derived starches-based microparticles and beads as sustained delivery carrier matrices prepared via the ionotropic-gelation technique. These ionotropically gelled beads and microparticles made of alginate–plant-derived starches were observed for the encapsulations of various drug candidates to facilitate sustained release of encapsulated drugs over a prolonged duration.

There is an increasing body of evidence demonstrating the importance of paracrine factors in a wide range of diseases. Paracrine factors such as growth factors and cytokines are soluble signaling proteins synthesized and secreted by cells and can diffuse over short distances to induce changes in neighboring cells. They act locally and show short and slow diffusion in the extracellular matrix to interact with their receptors to activate signaling pathways that control a variety of cellular processes such as proliferation, survival, migration, and differentiation. This chapter provides the latest advances in the development of different nanoparticulate systems for the delivery of paracrine factors to increase availability, preserve bioactivity, functionality and stability, and control release of paracrine factors to the region of interest.

This study was designed to investigate functionality of tetracycline‐loaded chitosan‐halloysite nanocomposite films, with focus on evaluating the influence of chitosan molar mass on films applicability for sustained local antibiotic delivery. The films were prepared by casting and solvent evaporation using low, medium, and high molar mass chitosan. SEM analysis revealed compact, nonporous and rough surface of the nanocomposite films due to the presence of halloysite agglomerates and tetracycline crystals. Increasing chitosan molar mass led to higher values of elongation at break (from 21.65 ± 2.65 to 34.48 ± 2.34%), tensile strength (from 134.8 ± 13.21 to 246.36 ± 14.69 MPa), and elastic modulus (from 633.79 ± 128.37 to 716.55 ± 60.76 MPa) of the nanocomposite films. FT‐IR, XRPD, and thermal analyses confirmed molar mass dependent chitosan‐halloysite interactions and improved thermal stability of the nanocomposite films in comparison with chitosan films. The nanocomposite films released tetracycline in a sustained manner, with the slowest release achieved from the films consisting of low molar mass chitosan. Chitosan molar mass was confirmed to be a functionality‐related characteristic of chitosan‐halloysite nanocomposite films as potential sustained‐release carriers for topical delivery of antibiotics. This is peer-reviewed version of the following article: Čalija, B.; Milić, J.; Milašinović, N.; Daković, A.; Trifković, K.; Stojanović, J.; Krajišnik, D. Functionality of Chitosan-Halloysite Nanocomposite Films for Sustained Delivery of Antibiotics: The Effect of Chitosan Molar Mass. J. Appl. Polym. Sci. 2020, 137 (8). [https://doi.org/10.1002/app.48406]

Humans have long demonstrated an enormous capacity to change landscapes, often very quickly. But these changes have either been unintentional or intended for a static, equilibrium world where the drivers of change were incremental and not accelerating at their current pace. How can landscapes be intentionally managed for change? I provide a brief summary of innovative management actions for the sustained delivery of landscape values into the manageable future. We have developed a vast array of tools for managing landscapes, some that are well-vetted and others that are novel and innovative. Using landscape trajectories as a framework, I provide an overview of these tools.

Polysaccharides are considered as the most promising natural materials for their unique physicochemical properties and excellent biocompatibility. They are biodegradable, non-toxic, abundant, and inexpensive biopolymeric precursors for preparing materials of choice in various industries. Many biomedical applications of polysaccharide nanomaterials (PNM) have been explored. PNM have the potential to be used as nanometric carriers for the sustained/controlled delivery of drugs. Sustained delivery through PNM has improved the utility of many drugs like 5 aminosalicylic acid, diclofenac sodium, ranitidine hydrochloride, and hormonal drugs while alleviating their toxic side effects. This chapter summarizes the recent developments in the field of PNM based drug delivery systems.

Controlled/sustained delivery systems have been developed rapidly which show the ability to overcome the obstacles of traditional delivery systems. Daily development of biomedical and biomaterial sciences has brought more attention to the implantable delivery systems. As a result, these systems have found their position in the medical field since they were introduced. The advances in the polymeric science along with the other fields, make the production of a wide variety of implantable systems, possible. The influence of these systems in medical field could not be denied Here', the pharmaceutical applications which have been mostly focused on, are discussed. Since these systems have proven to be beneficial, researchers are trying to adjust their defects to the desired properties. Doing so, the path that implantable delivery systems have crossed so far should be studied, and that's the aim of this review. In the present report, the advantages of these systems in chemotherapeutic, contraceptive, neuropsychology, pain management, peptide delivery, ocular delivery, cardiovascular, orthopedic, and dental fields have been evaluated.

Biomedical implant failure due to the host's response remains a challenging problem. In particular, the formation of the fibrous capsule is a common barrier for the normal function of implants. Currently, there is mounting evidence indicating that the polarization state of macrophages plays an important role in effecting the foreign body reaction (FBR). This opens up a potential avenue for improving host‐implant integration. Here, electrospun poly(caprolactone‐co ‐ethyl ethylene phosphate) nanofiber scaffolds are utilized to deliver microRNAs (miRs) to induce macrophage polarization and modulate FBR. Specifically, C57BL/6 mice that are treated with M2‐inducing miRs, Let‐7c and miR‐124, display relatively thinner fibrous capsule formation around the scaffolds at both Week 2 and 4, as compared to treatment with M1‐inducing miR, Anti‐Let‐7c. Histological analysis shows that the density of blood vessels in the scaffolds are the highest in miR‐124 treatment group, followed by Anti‐Let‐7c and Let‐7c treatment groups. Based on immunohistochemical quantifications, these miR‐encapsulated nanofiber scaffolds are useful for localized and sustained delivery of functional miRs and are able to modulate macrophage polarization during the first 2 weeks of implantation to result in significant alteration in host‐implant integration at longer time points. NRF (Natl Research Foundation, S’pore) MOE (Min. of Education, S’pore) NMRC (Natl Medical Research Council, S’pore) MOH (Min. of Health, S’pore) Accepted version

Anti-vascular endothelial growth factor (anti-VEGF) proteins are the gold-standard treatment for posterior eye segment proliferative vascular diseases such as Age-Related Macular Degeneration (AMD) and Diabetic Retinopathy (DR). However, the standard of care requires inconvenient monthly intravitreal injections. This underlies an unmet clinical need to develop alternative solutions for sustained delivery of biologics. In this paper, we demonstrated that anti-VEGFs can be encapsulated by a simple mild process into our polyurethane thermogel depots. By changing the hydrophilic-hydrophobic balance in the copolymer, anti-VEGF release rates can be modulated. The antibody in the thermogel partitions into protein domains which vary in size corresponding to the hydrophilicity balance of the polymer. Anti-VEGFs can be released in a relatively linear manner from the thermogel for up to 40 days in vitro. The encapsulated anti-VEGFs demonstrate anti-angiogenic bioactivity by inhibiting vessel outgrowth in rat ex vivo choroidal explants, and reducing vascular leakage in a VEGF-driven neovascularization rabbit model. In conclusion, we show that these thermogels can be tuned in terms of hydrophilicity and used for sustained delivery of bioactive anti-VEGFs. Physically cross-linked polyurethane thermoresponsive hydrogels could be a promising platform for sustained delivery of biologically active therapeutic proteins.

Inflammatory conditions of the temporomandibular joint (TMJ) and peripheral tissues affect many people around the world and are commonly treated with non-steroidal anti-inflammatory drugs (NSAIDs). However, in order to get desirable results, treatments with NSAIDs may take weeks, causing undesirable side effects and requiring repeated administration. In this sense, this work describes the development of an optimized nanostructured lipid carrier (NLC) formulation for intra-articular administration of naproxen (NPX). An experimental design (23) selected the best formulation in terms of its physicochemical and structural properties, elucidated by different methods (DLS, NTA, TEM, DSC, and ATR-FTIR). The chosen formulation (NLC-NPX) was tested on acute inflammatory TMJ nociception, in a rat model. The optimized excipients composition provided higher NPX encapsulation efficiency (99.8%) and the nanoparticles were found stable during 1 year of storage at 25 °C. In vivo results demonstrated that the sustained delivery of NPX directly in the TMJ significantly reduced leukocytes migration and levels of pro-inflammatory cytokines (IL-1β and TNF-α), for more than a week. These results point out the NLC-NPX formulation as a promising candidate for the safe treatment of inflammatory pain conditions of TMJ or other joints.

Traditional patches are most successful in transdermal delivery of low-dose hydrophobic drugs. Week-long transdermal delivery of high-dose hydrophilic drugs remains a big challenge. This study explored ablative fractional laser (AFL) to assist 3-day to week-long sustained transdermal delivery of powder hydrophilic drugs in murine models. Bulk drug powder was coated into reservoir patches followed by topical application onto AFL-treated skin. Water evaporated from AFL-generated skin microchannels (MCs) gradually dissolve topical drug powder to elicit multi-day sustained drug delivery. Using sulforhodamine b, zidovudine, and bovine serum albumin as model hydrophilic drugs, we found tapped coating could coat 10–20 mg drug per 0.5 cm(2) reservoir patch to elicit 3-day sustained delivery, while compression coating could coat ~35–70 mg drug per 0.5 cm(2) reservoir patch to elicit week-long sustained delivery. Besides sustained drug delivery, AFL-assisted powder reservoir patch delivery also showed a good safety. AFL-generated skin MCs resealed in 1–2 days and completely recovered in 3 days after the week-long sustained delivery. AFL-assisted powder reservoir patch delivery involves no complex powder formulation and only requires incorporation of highly water-soluble mannitol or a similar excipient to elicit the high-efficient delivery. Enlarging reservoir patch size to 10 cm(2) can conveniently expands the delivery capacity to gram scale. To our knowledge, this is the first time that high-dose week-long sustained transdermal delivery of hydrophilic drugs was achieved via a simple laser-based powder delivery platform.

Controlled, localized drug delivery is a long-standing goal of medical research, realization of which could reduce the harmful side-effects of drugs and allow more effective treatment of wounds, cancers, organ damage and other diseases. This is particularly the case for protein “drugs” and other therapeutic biological cargoes, which can be challenging to deliver effectively by conventional systemic administration. However, developing biocompatible materials that can sequester large quantities of protein and release them in a sustained and controlled manner has proven challenging. Glycosaminoglycans (GAGs) represent a promising class of bio-derived materials that possess these key properties and can additionally potentially enhance the biological effects of the delivered protein. They are a diverse group of linear polysaccharides with varied functionalities and suitabilities for different cargoes. However, most investigations so far have focused on a relatively small subset of GAGs – particularly heparin, a readily available, promiscuously-binding GAG. There is emerging evidence that for many applications other GAGs are in fact more suitable for regulated and sustained delivery. In this review, we aim to illuminate the beneficial properties of various GAGs with reference to specific protein cargoes, and to provide guidelines for informed choice of GAGs for therapeutic applications.

Sustained and/or controlled release of biological agents is a concept that has received a great deal of attention during the past decade. Systems designed to release drugs at a rate directly influenced by the nature of their surrounding environment will be referred to as sustained delivery devices. Drug delivery devices designed to release drug at a predetermined rate influenced to a large extent by the nature of their fabrication, and not to a significant extent by environmental interaction, will be referred to as controlled delivery systems. The primary goal of sustained or controlled drug release is the prolonged delivery of a drug to a particular body compartment or anatomical target site. For many drug systems, the parent drug may be the only active drug species and consideration of individual drug metabolites within the kinetic model may not be of significant clinical importance.

Medicinal and aromatic plants are natural raw materials. Since ancient times these herbal materials are being commonly used as herbal drugs, food products, and cosmetics. The phytomolecules isolated from the medicinal and aromatic plants (MAPs) are in high demand specifically in drug industries. However, these phytomolecules have certain limitations of low absorption, high toxicity, and other side effects, bioavailability and efficacy. These limitations may be overcome by using nanotechnological tools. The plant extract or essential oil of MAPs are also useful in the synthesis of nanoparticles. In future this combinatorial application of MAPs and nanotechnology would be advantageous in the healthcare area.Literature search was performed using databases like Pubmed, Scopus and Google Scholar with the keywords "nanoparticles," "phytomolecules," "medicinal and aromatic plants" and "green synthesis of nanoparticles" in the text.Phytomolecules of medicinal and aromatic plants like curcumin, camptothecin, thymol, and eugenol have certain limitations of bioavailability, efficacy, and solubility. It limits its biological activity and therefore application in the biomedical area. The increment in the biological activity and sustained delivery was observed after the encapsulation of these potent phytomolecules encapsulated in the nanocarriers. Besides, MAPs and/or their molecules/oils mediate the synthesis of metal nanocarriers with less toxicity.This review highlights the impact of the combination of the MAPs with the nanotechnology along with the challenges. It would be an effective technique for the efficient delivery of different phytomolecules and also in the synthesis of novel nano-materials, which escalates the opportunity of exploration of potential molecules of MAPs. Graphical abstract Graphical representation of the combinatorial approach of MAPs and nanotechnology.

A novel system of delivery presents many advantages such as sustained delivery, higher bioavailability, improved medication compliance, and therapeutic outcomes, patient monitoring, and minor side effects. One of the improved ways of drug delivery is electronic capsules which can deliver drugs to a specific site in the gastrointestinal tract and can also be used for patient monitoring. Wireless transdermal patches are a novel electronic drug delivery system, which is portable, disposable and worn on the skin surface to deliver medications on the transdermal level. Electronic transdermal drug delivery has made a major contribution to clinical practice due to improving the efficiency of drug delivery over the conventional route. The improvement can provide a solution for getting rid of the bondage of batteries as well as the restrictions of inconvenient wires, on self-powered systems. The greatest achievement of wireless transdermal patches is the ability to further improve transdermal drug delivery for certain drugs that could not be administered using conventional transdermal patches. Electronic drug delivery systems such as capsules, on the other side, can be used not only to deliver drugs to a specific site in the gastrointestinal tract but can also record data and report the state of patients gastrointestinal tract, and after excretion, this information can be studied and used to present them graphically.

Cardiovascular diseases have continued to remain a leading cause of mortality and morbidity worldwide. Poor proliferation capability of adult cardiomyocytes disables the heart from regenerating new myocardium after a myocardial ischaemia event and therefore weakens the heart in the long term, which may result in heart failure and death. Delivery of cardioprotective therapeutics soon after the event can help to protect the heart from further cell death and improve cardiac function, but delivery methods and potential side effects of these therapeutics may be an issue. Advances in nanotechnology, particularly nanoparticles for drug delivery, have enabled researchers to obtain better drug targeting capability, thus increasing the therapeutic outcome. Detailed study of nanoparticles in vivo is useful as it can provide insight for future treatments. Nanogel can help to create a more favourable environment, not only for a sustained delivery of therapeutics, but also for a better navigation of the therapeutics to the targeted sites. Finally, if the damage to the myocardium is too severe for drug treatment, nanopatch can help to improve cardiac function and healing by becoming a platform for pluripotent stem cell-derived cardiomyocytes to grow for the purpose of cell-based regenerative therapy.

The sustained delivery of extracellular vesicles, secreted by induced-pluripotent-stem-cell-derived cardiomyocytes, through a hydrogel patch promotes cardiac recovery after myocardial infarction in rats.

Osteogenic peptides have been reported as highly effective in directing mesenchymal stem cell osteogenic differentiation in vitro and bone formation in vivo. Therefore, developing novel biomaterials for the controlled delivery of osteogenic peptides in scaffolds without lowering the peptide&rsquo, s biological activity is highly desirable. To repair a critical-sized bone defect to efficiently achieve personalized bone regeneration, a novel bioactive poly(lactic-co-glycolic acid) (PLGA)/&beta, tricalcium phosphate (&beta, TCP) composite scaffold, in which graphene oxide (GO) and bone morphogenetic protein (BMP)-2-like peptide were loaded in situ (PTG/P), was produced by an original cryogenic 3D printing method. The scaffolds were mechanically comparable to human cancellous bone and hierarchically porous. The incorporation of GO further improved the scaffold wettability and mechanical strength. The in situ loaded peptides retained a high level of biological activity for an extended time, and the loading of GO in the scaffold further tuned the peptide release so that it was more sustained. Our in vitro study showed that the PTG/P scaffold promoted rat bone marrow-derived mesenchymal stem cell ingrowth into the scaffold and enhanced osteogenic differentiation. Moreover, the in vivo study indicated that the novel PTG/P scaffold with sustained delivery of the peptide could significantly promote bone regeneration in a critical bone defect. Thus, the novel bioactive PTG/P scaffold with a customized shape, improved mechanical strength, sustainable peptide delivery, and excellent osteogenic ability has great potential in bone tissue regeneration.

The objective of this study was to quantitatively evaluate the possible morphological alterations that occur in the columnar epithelial cells of the prostate peripheral zone during early development of benign prostatic hyperplasia (BPH). In this study, BPH was induced by the continuous and sustained delivery of Danazol (androgen analog) through tricalcium phosphate-lysine (TCPL) drug delivery devices (OD: 0.8 mm, ID: 0.4 mm and density: 1.98 ± 0.53 gm/cm3). A total of 24 adult male rats (BW: 280-320 gm) were randomly divided into three equal groups. Group 1 served as an intact control and Groups 2-3 were implanted with TCPL devices designed to deliver continuous physiologic (3-5 ng/ml) doses of Danazol (DZ) following standard laboratory surgical methods. Upon completion of the study (12 weeks), the resected prostate were subjected to histopathological evaluation. Specifically, the columnar epithelial cells were targeted for morphometric analysis. The means number of cells per high power field, cell length, cell area; nuclear area and nuclear to cytoplasmic ratio (N/C) were measured using digital image analysis software technique. The results of this study revealed that: (i) the number of cells per high power field were unchanged with DZ exposure (log 1.22 ± 0.32) compared to controls (log 1.22 ± 0.26); (ii) the cell length was significantly (P < 0.05) decreased with upon DZ exposure (0.9 ± 0.03 µm) compared to controls (1.32 ± 0.51 µm), (iii) the cellular area was decreased with DZ (1.02 ± 0.056 µm 2) compared to controls (1.59 ± 0.102 µm 2 , and (iv) the N/C ratio was increased (0.279 ± 0.032 um) compared to controls (0.188 ± 0.021 µm). The results of this study suggest that sustained delivery of DZ by TCPL modality resulted in a remarkable alteration during early development of BPH. These finding may alert a pre-dysplastic outcomes from sustained delivery of DZ.

We propose an elastic net made of a biocompatible polymer to wrap silicone implants of various sizes, which also allows for the sustained release of an anti-inflammatory drug, triamcinolone, to prevent fibrosis. For this, we first prepared a strand composed of a mixture of polyurethane and triamcinolone via electrospinning, which was then assembled to prepare the elastic drug-delivery net (DDN). The DDN was prepared to just fit for wrapping the small silicone implant sample herein, but was also able to wrap a sample 7 times as large at 72% strain due to the elastic property of polyurethane. The DDN exhibited sustained drug release for 4 weeks, the profile of which was not very different between the intact and strained DDNs. When implanted in a subcutaneous pocket in living rats, the DDN-wrapped silicone implant samples showed an obvious antifibrotic effect due to the sustained release of triamcinolone. Importantly, this effect was similar for the small and large silicone samples, both wrapped with the same DDN. Therefore, we conclude that this drug-loaded net made of an elastic, biocompatible polymer has high potential for sustained drug delivery around silicone implants manufactured in various sizes.

Routes of drug administration and the corresponding physicochemical characteristics of a given route play significant roles in therapeutic efficacy and short term/long term biological effects. Each delivery method has favorable aspects and limitations, each requiring a specific delivery vehicles design. Among various routes, oral delivery has been recognized as the most attractive method, mainly due to its potential for solid formulations with long shelf life, sustained delivery, ease of administration and intensified immune response. At the same time, a few challenges exist in oral delivery, which have been the main research focus in the field in the past few years. The present work concisely reviews different administration routes as well as the advantages and disadvantages of each method, highlighting why oral delivery is currently the most promising approach. Subsequently, the present work discusses the main obstacles for oral systems and explains the most recent solutions proposed to deal with each issue.

Over the years, extensive studies on erythrocytes, also known as red blood cells (RBCs), as a mechanism for drug delivery, have been explored mainly because the cell itself is the most abundant and has astonishing properties such as a long life span of 100-120 days, low immunogenicity, good biocompatibility, and flexibility. There are various types of RBC-based systems for drug delivery, including those that are genetically engineered, non-genetically engineered RBCs, as well as employing erythrocyte as nanocarriers for drug loading. Although promising, these systems are still in an early development stage. In this review, we aimed to highlight the development of biomimicking RBC-based drug and vaccine delivery systems, as well as the loading methods with illustrative examples. Drug-erythrocyte associations will also be discussed and highlighted in this review. We have highlighted the possibility of exploiting erythrocytes for the sustained delivery of drugs and vaccines, encapsulation of these biological agents within the erythrocyte or coupling to the surface of carrier erythrocytes, and provided insights on genetically- and non-genetically engineered erythrocytes-based strategies. Erythrocytes have been known as effective cellular carriers for therapeutic moieties for several years. Herein, we outline various loading methods that can be used to reap the benefits of these natural carriers. It has been shown that drugs and vaccines can be delivered via erythrocytes but it is important to select appropriate methods for increasing the drug encapsulated or conjugated on the surface of the erythrocyte membrane. The outlined examples will guide the selection of the most effective method as well as the impact of using erythrocytes as delivery systems for drugs and vaccines.