Nasal Delivery to the Brain: Harnessing Nanoparticles for Effective Drug Transport.

The nose-to-brain drug-delivery system has emerged as a promising strategy to overcome the challenges associated with conventional drug administration for central nervous system disorders. This emerging field is driven by the anatomical advantages of the nasal route, enabling the direct transport of drugs from the nasal cavity to the brain, thereby circumventing the blood-brain barrier. This review highlights the significance of the anatomical features of the nasal cavity, emphasizing its high permeability and rich blood supply that facilitate rapid drug absorption and onset of action, rendering it a promising domain for neurological therapeutics. Exploring recent developments and innovations in different nanocarriers such as liposomes, polymeric nanoparticles, solid lipid nanoparticles, dendrimers, micelles, nanoemulsions, nanosuspensions, carbon nanotubes, mesoporous silica nanoparticles, and nanogels unveils their diverse functions in improving drug-delivery efficiency and targeting specificity within this system. To minimize the potential risk of nanoparticle-induced toxicity in the nasal mucosa, this article also delves into the latest advancements in the formulation strategies commonly involving surface modifications, incorporating cutting-edge materials, the adjustment of particle properties, and the development of novel formulations to improve drug stability, release kinetics, and targeting specificity. These approaches aim to enhance drug absorption while minimizing adverse effects. These strategies hold the potential to catalyze the advancement of safer and more efficient nose-to-brain drug-delivery systems, consequently revolutionizing treatments for neurological disorders. This review provides a valuable resource for researchers, clinicians, and pharmaceutical-industry professionals seeking to advance the development of effective and safe therapies for central nervous system disorders.

Lipid-based Nanoparticulate Drug Delivery.

The emergence of lipid-based nanoparticulate systems has significantly reshaped the landscape of drug delivery. This review encapsulates the advancements, challenges, and potential of lipid-based nanoparticulate drug delivery in modern therapeutics. Lipid-based nanoparticles, including liposomes, lipid nanoparticles, and solid lipid nanoparticles, harness the biocompatibility and biodegradability of lipids to encapsulate and deliver a diverse range of therapeutic agents. This platform offers solutions to various drug delivery challenges, such as enhancing drug solubility and bioavailability, achieving controlled and sustained release, targeted delivery, and co-delivery of multiple agents. These nanoparticles have demonstrated potential in overcoming biological barriers, including the blood-brain barrier, mucosal barriers, and cellular barriers, enabling the delivery of drugs to previously inaccessible sites. Biocompatibility and reduced toxicity are intrinsic attributes of lipid-based nanoparticles, minimizing immune responses and systemic toxicity while promoting personalized medicine possibilities. However, challenges in formulation, stability, and regulatory approval underscore the need for ongoing research and innovation in this field.

Ocular Delivery of Therapeutic Proteins: A Review.

Therapeutic proteins, including monoclonal antibodies, single chain variable fragment (ScFv), crystallizable fragment (Fc), and fragment antigen binding (Fab), have accounted for one-third of all drugs on the world market. In particular, these medicines have been widely used in ocular therapies in the treatment of various diseases, such as age-related macular degeneration, corneal neovascularization, diabetic retinopathy, and retinal vein occlusion. However, the formulation of these biomacromolecules is challenging due to their high molecular weight, complex structure, instability, short half-life, enzymatic degradation, and immunogenicity, which leads to the failure of therapies. Various efforts have been made to overcome the ocular barriers, providing effective delivery of therapeutic proteins, such as altering the protein structure or including it in new delivery systems. These strategies are not only cost-effective and beneficial to patients but have also been shown to allow for fewer drug side effects. In this review, we discuss several factors that affect the design of formulations and the delivery of therapeutic proteins to ocular tissues, such as the use of injectable micro/nanocarriers, hydrogels, implants, iontophoresis, cell-based therapy, and combination techniques. In addition, other approaches are briefly discussed, related to the structural modification of these proteins, improving their bioavailability in the posterior segments of the eye without affecting their stability. Future research should be conducted toward the development of more effective, stable, noninvasive, and cost-effective formulations for the ocular delivery of therapeutic proteins. In addition, more insights into preclinical to clinical translation are needed.

Pharmacokinetic Evaluation of Thermosensitive Sustained Release Formulations Developed for Subcutaneous Delivery of Protein Therapeutics.

Injectable, thermosensitive hydrogels, constructed from cross-linked polymers, can offset the limitations of other sustained release delivery systems, overcome constrains of available therapies, and improve patient compliance to chronic therapy. The goal of this project was to identify and evaluate such sustained release, in situ formulations that can help achieve prolonged exposure of protein therapeutics with a short systemic half-life. Natural polymers were used to develop injectable, thermosensitive in situ hydrogels and single-chain variable fragment (scFv) of trastuzumab was used as the model protein with a short half-life. The three polymer combinations tested were: (1) Chitosan and ß-glycerophosphate, (2) Chitosan, ß-glycerophosphate, and Hyaluronic Acid, and (3) Hyaluronic Acid and Dextran. In vitro drug release experiments were conducted, using different combinations of various polymer concentrations and different drug loading amounts, to identify optimal combinations with prolonged and controlled drug release while exhibiting minimal burst release effect. Select formulations were injected subcutaneously in normal mice to evaluate the pharmacokinetics of scFv for 14 days and identify drug release kinetics in vivo. A two-compartment PK model was also established to quantitatively characterize the release kinetics and disposition of scFv following in vivo administration of the hydrogels. The scFv was undetectable in plasma after 4 and 24 hours following intravenous and subcutaneous administration, respectively. However, all three hydrogel systems were found to provide controlled release of scFv in vivo and maintain detectable concentrations of scFv for at least 14 days. The results suggested that subcutaneous injection of thermosensitive in situ hydrogels may be used to achieve sustained exposure of protein therapeutics which have a very short half-life and thus require frequent administration.

Effective Delivery Routes And Strategies For Solid Lipid Nanoparticles (Sln) And Nanostructured Lipid Carriers (Nlc).

BACKGROUND: SLNs and NLCs have remarkably wide range of properties which make them useful for several potential applications in drug delivery, clinical medicine, and research, as well as in parenteral, dermal, pulmonary and topical delivery of drugs. The unique size-dependent properties of the solid lipid nanoparticles make them at the forefront of the rapidly developing field of nanotechnology offering development of new therapeutics having reduced toxic side effects and increased treatment efficacy. METHODS: SLNs and NLCs are very attractive drug delivery candidates, primarily due to their relatively stable constituents and probable ease of drug encapsulations. The incorporation of drugs into nanocarriers like SLNs and NLCs for several levels of drug targeting offers good potential in gene transfer, cosmetic and food industry with great promise for reaching the goal of controlled and site-specific drug delivery. Lipid nanoparticle drug delivery technology presents considerable opportunities for improving medical therapeutics, but the technology's potential remains unrealized. RESULTS: The review has focused on the various effective delivery routes and strategies for SLNs and NLCs, and their applicability in the encapsulation of therapeutics. Number of research works has been successfully carried out in this area. It would result in a simultaneous improvement in the quality, efficacy, and safety profile of drugs. CONCLUSION: However, because of mentioned limitations and difficulties related to them, the total number of products on the market is still limited. Although the concept of PEGylation to increase half-life of nanoparticles revolutionized the nanoparticle-mediated drug-delivery field, significant improvements are warranted in this area.

Design and Characterization of Buccoadhesive Liquisolid System of an Antihypertensive Drug.

Nifedipine is an antihypertensive BCS class II drug which has poor bioavailability when given orally. The objective of the present study was to increase the bioavailability of nifedipine, by formulation and evaluation of a buccoadhesive liquisolid system using magnesium aluminium silicate (Neusilin) as both carrier and coating material and dissolution media were selected based on the solubility studies. A mixture of carboxymethylcellulose sodium and carbomer was used as mucoadhesive polymers. Buccoadhesive tablets were prepared by direct compression. FTIR studies confirmed no interaction between drug and excipients. XRD studies indicated change/reduction in crystallinity of drug. The powder characteristics were evaluated by different flow parameters to comply with pharmacopoeial specifications. The dissolution studies for liquisolid compacts and tablet formulations were carried out and it was found that nifedipine liquisolid tablets formulated from bioadhesive polymers containing 49% liquisolid system, 17.5% carbomer, and 7.5% carboxymethylcellulose sodium showed the best results in terms of dissolution properties. Prepared formulation batches were evaluated for swelling, bioadhesion strength, ex vivo residence time, and permeability studies. The optimized batch was showing promising features of the system. Formulating nifedipine as a buccoadhesive tablet allows reduction in dose and offers better control over the plasma levels.

Thermoreversible mucoadhesive ophthalmic in situ hydrogel: Design and optimization using a combination of polymers.

The purpose of the study was to develop an optimized thermoreversible in situ gelling ophthalmic drug delivery system based on Pluronic F 127, containing moxifloxacin hydrochloride as a model drug. A 3(2) full factorial design was employed with two polymers: Pluronic F 68 and Gelrite as independent variables used in combination with Pluronic F 127. Gelation temperature, gel strength, bioadhesion force, viscosity and in vitro drug release after 1 and 10 h were selected as dependent variables. Pluronic F 68 loading with Pluronic F 127 was found to have a significant effect on gelation temperature of the formulation and to be of importance for gel formation at temperatures 33-36 °C. Gelrite loading showed a positive effect on bioadhesion force and gel strength and was also found helpful in controling the release rate of the drug. The quadratic mathematical model developed is applicable to predicting formulations with desired gelation temperature, gel strength, bioadhesion force and drug release properties.