Areas covered: In this article, the effects of excipients and particle preparation methods on the properties of solid lipid nanocarriers (SLNCs) and their impact on drug absorption and efficacies related to different administration routes are reviewed and discussed.
Expert opinion: SLNCs have special characteristics, making them attractive as drug delivery systems, for parenteral and oral delivery for systemic effects, or ocular, pulmonary and topical delivery to enhance local treatment efficacy and reducing systemic side effects. Both excipients and fabrication methods are crucial for the function and size of nanoparticles and should be considered simultaneously in designing particles to obtain the optimal drug absorption and efficacy, especially for local treatments. Despite the demonstrated advantages by the preclinical studies, further studies on improved understanding of the interactions of SLNCs with biological tissues of the target site is necessary for efficient designing functional nanoparticles for clinical applications.
Abbreviations: DG: diglycerides; FFA: free fatty acids; GMS: glyceryl monostearate; MG: monoglycerides; NLC: nanostructured lipid carriers; PL: phospholipids; SLM: solid lipid microparticles; SLN: solid lipid nanoparticles; SLNC: solid lipid nanocarriers; TG: triglycerides. 相似文献
Areas covered: Transporters and enzymes expressed on BCSFB and brain parenchyma and their impact on drug brain uptake were highlighted and compared with that on BBB.
Expert opinion: Based on the nature of transporters expressed on BCSFB and the brain parenchyma, the design of CNS therapeutics with chemical structures similar to the substrates of nutrients and hormones transporters could facilitate their CSF and brain parenchyma uptake . Moreover, drugs in systemic circulation could undergo further metabolism at BCSFB and brain parenchyma leading to failure in CNS drug delivery. Impact of the altered expressions and functions of transporters and enzymes on BCSFB and brain parenchyma in different species or disease conditions on CNS drug brain uptake shall be further evaluated using relevant in vitro cell models and pharmacokinetics modeling. 相似文献
Areas covered: This review focuses on nanotechnology-based drug delivery platforms designed for selective recruitment into the lesioned brain by taking advantages of BBB disruption that is associated with certain neurological conditions.
Expert opinion: Current CNS therapeutic strategies do not fully address the pathophysiological adaptation of BBB in their design. The lack of selective delivery to the brain lesions has been the culprit behind the failure of many CNS therapeutics. This highlighted the need for smart designs of advanced drug delivery systems that take advantage of BBB structural changes in CNS diseases. Recently, promising examples have been reported in this area, however, more work is still required beyond the preclinical testing. 相似文献
Areas covered: This review highlights the barrier to the posterior segment of the eye via topical administration. The up-to-date development of lipid nanoparticles, liposomes, emulsions, spanlastics, micelles, polymeric nanoparticles, layered double hydroxides (LDH), dendrimers, cyclodextrins(CDs), and prodrugs are summarized. Moreover, nanocarriers currently in clinical trials for posterior segment diseases have been discussed.
Expert opinion: Topical nanoparticle-based drug delivery systems have demonstrated significant progress. An ideal formulation should prolong retention time on the surface, enhance drug permeability through the ocular tissues, and efficiently deliver drugs to the targeted site. To design the rational targeting nanoparticle-based drug delivery system, a better understanding of the distribution of transporters and receptors on the eye is required. Ultimately, there is an urgent need to develop targeting hybrid drug delivery systems with the combination of the advantages of several nanocarriers. 相似文献
Areas covered: This review focuses on NIR-responsive characteristics of different NIR-nanobiophotonics-based nanoagents and associated drug delivery strategies. Together with their ongoing applications for peripheral drug delivery, we have highlighted the opportunities, challenges and possible solutions of NIR-nanobiophotonics for potential brain drug delivery.
Expert opinion: NIR-nanobiophotonics can be considered superior among all photo-controlled drug/gene delivery approaches. Future work should focus on coupling NIR with biocompatible nanocarriers to determine the physiological compatibility of this approach. Their applications should be extended beyond the peripheral body region to brain region. Transient or intermittent NIR exposure strategies may be more accommodating for brain physiological ambience in order to minimize or avoid the possible deleterious thermal effect. In addition, while most studies are centered around the first NIR spectral window (700–1000 nm), the potential of second (1100–1350 nm) and third (1600–1870 nm) windows must be explored. 相似文献
Areas covered: Following an overview of the different ocular drug delivery modalities, this article surveys the biomaterials used to develop sustained release drug delivery systems. Microspheres, nanospheres, liposomes, hydrogels, and composite systems are discussed in terms of their primary materials. The advantages and disadvantages of each drug delivery system are discussed for various applications. Recommendations for modifications and strategies for improvements to these basic systems are also discussed.
Expert opinion: An ideal sustained release drug delivery system should be able to encapsulate and deliver the necessary drug to the target tissues at a therapeutic level without any detriment to the drug. Drug encapsulation should be as high as possible to minimize loss and unless it is specifically desired, the initial burst of drug release should be kept to a minimum. By modifying various biomaterials, it is possible to achieve sustained drug delivery to both the anterior and posterior segments of the eye. 相似文献
Areas covered: We review organic NP carriers based on polymers, proteins, peptides, and lipids for simultaneous delivery of multiple anticancer drugs, drug/sensitizer combinations, drug/photodynamic therapy or drug/photothermal therapy combinations, and drug/gene therapeutics with examples in the past three years. Sequential delivery of drug combinations, based on either sequential administration or built-in release control, is introduced with an emphasis on the mechanistic understanding of such control.
Expert opinion: Recent studies demonstrate how a drug carrier can contribute to co-localizing drug combinations in optimal ratios and dosing sequences to maximize the synergistic effects. We identify several areas for improvement in future research, including the choice of drug combinations, circulation stability of carriers, spatiotemporal control of drug release, and the evaluation and clinical translation of combination delivery. 相似文献
Areas covered: This review describes nasal anatomy, routes of stem cell migration, and factors affecting stem cell delivery to hard-to-reach tumors. Furthermore, this review discusses the molecular mechanisms underlying stem cell migration following delivery, as well as possible stem cell effector functions to be considered in combination with intranasal delivery.
Expert opinion: Further research is necessary to elucidate the dynamics of stem cell effector functions in the context of intranasal delivery and optimize their therapeutic potency. Nonetheless, the technique represents a promising tool against brain cancer and has the potential to be expanded for use against other brain pathologies. 相似文献
Areas covered: The current review gives a broadscope on zein as a still promising protein excipient in different fields. Zein- based drug and biomedical delivery systems are discussed with special focus on current and potential application in controlled drug delivery systems, and tissue engineering.
Expert opinion: Zein as a protein of natural origin can still be considered a promising polymer in the field of drug delivery systems as well as in tissue engineering. Although different researchers spotted light on zein application in different industrial fields extensively, the feasibility of its use in the field of drug delivery replenished by investigators in recent years has not yet been fully approached. 相似文献
Area covered: This review highlighted the morphology of skin, its barrier nature as well as drug penetration pathways after topical application of formulations. The existing methods to improve topical drug delivery, by infringing or permeating the skin barriers, are discussed. This context concretes the foundation to accentuate the need for the development of nanocrystal-based topical formulation. The mechanism of drug release, immediate as well as sustained release, after topical administration of drug nanocrystals is also elaborated. The special emphasis is given on the breakthrough achieved, in topical drug delivery using drug nanocrystals, so far in the plethora of literature, patents, and products, under clinical trial as well as in the market.
Expert opinion: The current research on nanocrystals for topical drug delivery is highlighting the breakthroughs achieved so far. The output of these research envisages that topical nanocrystals based formulations can be a novel strategy for the drugs which are facing solubility, bioavailability and toxicity concerns. 相似文献
Areas covered: This review summarises the synthesis methods for producing rod-shaped mesoporous silica nanoparticles for use in nanomedicine. The second part covers recent progress of mesoporous silica nanorods by comparing the impact of sphere and rod-shape on drug delivery efficiency.
Expert opinion: As hollow mesoporous silica nanorods are capable of higher drug loads than most other drug delivery vehicles, such particles will reduce the amount of mesoporous silica in the body for efficient therapy. However, the importance of nanoparticle shape on drug delivery efficiency is not well understood for mesoporous silica. Studies that visualize and quantify the uptake pathway of mesoporous silica nanorods in specific cell types and compare the cellular uptake to the well-studied nanospheres should be the focus of research to better understand the role of shape in uptake. 相似文献
Areas covered: This review provides an overview of microfluidic devices and materials used for their manufacturing, together with the flow patterns and regimes commonly used for nanoparticle preparation. Additionally, the different geometries used in droplet microfluidics are reviewed, with particular attention to the co-flow geometry used for the production of nanoparticles. Finally, this review summarizes the main and most recent nanoparticulate systems prepared using microfluidics, including drug nanosuspensions, polymeric, lipid, structured, and theranostic nanoparticles.
Expert opinion: The production of nanoparticles at industrial scale is still a challenge, but the microfluidic technologies bring exciting opportunities to develop drug delivery systems that can be engineered in an easy, cost-effective and reproducible manner. As a highly interdisciplinary research field, more efforts and general acceptance are needed to allow for the translation of nanoparticulate drug delivery systems from academic research to the clinical practice. 相似文献
Areas covered: In recent years, several studies have been reported in the literature describing the utility of OCTN2 to enhance the delivery of drugs, prodrugs and nanoparticles. Here we summarize the salient features of OCTN2 in terms of its role in the cellular uptake of its physiological substrate L-carnitine in physiological and pathological context; the structural requirements for recognition and the recent advances in OCTN2-targeted drug delivery systems, including prodrugs and nanoparticles, are discussed.
Expert opinion: This transporter has great potential to be utilized as a target for drug delivery to improve oral absorption of drugs in the intestinal tract. It also has potential to facilitate the transfer of drugs across the biological barriers such as the blood-brain barrier, blood-retinal barrier, and maternal-fetal barrier. 相似文献
Areas covered: This review article seeks to provide an overview of a range of challenges that are often faced to achieve efficient ocular drug levels within targeted tissue(s) of the eye. It also describes the problems encountered using conventional hypodermic needle-based ocular injections for anterior and posterior segment drug delivery. It discusses research carried out in the field of MNs, to date.
Expert opinion: MNs can aid in localization of drug delivery systems within the selected ocular tissue. And, hold the potential to revolutionize the way drug formulations are administered to the eye. However, the current limitations and challenges of MNs application warrant further research in this field to enable its widespread clinical application. 相似文献
Areas covered: From solubility enhancement to targeted delivery, the nanoparticulate system became the answer for almost all the criticality related to drug delivery. Hence, nanoparticulate drug carrier system has been widely utilizing to remove the hurdles of brain drug delivery. Keeping this in mind, we have underlined the proficiencies of the nanocarrier systems which claim to improve the drug efficacy for the treatment of the AD.
Expert opinion: The nanotechnological approaches are highly exploited by the researchers to enhance the drug permeation across the BBB to improve its bioavailability and efficacy by protecting the drug from peripheral degradation. However, still in this area of drug targeting provides vast scope for discoveries towards the enhancement of drug efficacy through surface modifications, site specification, reduced toxicity of the nanocarrier system and so on. 相似文献
Areas covered: Current review includes an overview of ILS, factors governing lymphatic transport of nanoparticles and absorption mechanism of lipid and polymeric nanoparticles into ILS. Various ligands used to target Peyer’s patch and their conjugation strategies to nanoparticles are explained in detail. In vitro and in vivo models used to assess intestinal lymphatic transport of molecules are discussed further.
Expert opinion: Although ILS offers a versatile pathway for nanotechnology based targeted drug delivery, extensive investigations on validation of the lymphatic transport models and on the strategies for gastric protection of targeted nanocarriers have to be perceived in for excellent performance of ILS in oral drug delivery. 相似文献
Areas covered: This review article systemically generalized the major physiological barriers facing oral macromolecule delivery as well as the current approaches and novel developments in the field, including permeation enhancers, enzyme inhibitors, particulate drug delivery system, ligand delivery system, mucoadhesive delivery system, mucus penetration delivery system and other strategies.
Expert opinion: The development of composite formulation methods need to meet regulatory requirements for reproducibility, manufacturing cost, and bioavailability. So far, oral delivery of protein and peptide drugs is still facing immense challenges despite of the fact that some clinical studies are undergoing. The most advanced clinical strategies for therapeutic proteins are co-administration of absorption enhancers or protease inhibitors. Besides, rising new technologies in the field also provides a growing opportunity, such as nanotechnology, mucoadhesive and mucus penetration particulate delivery system. 相似文献
Areas covered: The review in its first part shortly describes the LBDDS, nanoemulsions and clarifies the ambiguity between nanoemulsions and microemulsions. In the second part, the review discusses SNEDDS and elaborates on the current developments and modifications in this area without discussing their associated preparation techniques and excipient properties.
Expert opinion: SNEDDS have exhibit the potential to increase the bioavailability of poorly water soluble drugs. The stability of SNEDDS is further increased by solidification. Controlled release and supersaturation can be achieved, and are associated with increased patient compliance and improved drug loads, respectively. Presence of biodegradable ingredients and ease of large-scale manufacturing combined with a lot of ‘drug-targeting opportunities’ give SNEDDS a clear distinction and prominence over other solubility enhancement techniques. 相似文献
Areas covered: Some of the prominently discussed nanoparticles in this day and age are polymeric micelles, liposomes, lipid–polymer hybrid nanoparticles, dendrimers, spongosomes and cubosomes. This review attempts to focus on the conventional advantages and exemplary features that these particles possess, thus making them some of the most ideal vehicles for drug delivery.
Expert opinion: Particulate systems, which have been extensively studied in this article, have been employed to enhance the pharmacokinetic and pharmacodynamic characteristics of various hydrophobic and hydrophilic drug moieties, thus attempting to prolong the blood circulation times and increase their efficacy over unmodified drug molecules. These modification techniques have enabled these drug molecules to be delivered to the pharmacological sites of action at an optimised controlled rate, thus trying to minimise the potential for any toxicity resulting from the non-specific distribution of drug to various organs. 相似文献