Non-invasive Drug Delivery System Research Articles

Non-invasive, continuous oral delivery of solid levodopa-carbidopa for management of Parkinson's disease.

When short plasma half-life drugs act only briefly, they require frequent or continuous administration. We report the engineering of a non-invasive oral drug delivery system for long-term, continuous administration of these drugs. Their non-invasive, long-term, continuous administration at daily doses exceeding 100 mg has, for many years, been considered an insurmountable challenge. We show that over 1200 mg/day of 4:1 levodopa-carbidopa (LD-CD) can be non-invasively and continuously extruded when formulated as a semisolid paste, loaded with 63%w/w of the solid drugs. The drug delivery system comprises a reusable orthodontic retainer with a co-molded pocket into which the patient inserts after each meal a new 1 mL propellant-driven, prefilled, disposable, drug delivery extruder. The paste is delivered to the lingual side of the teeth where it is mixed with saliva and swallowed. As reported elsewhere, a 15-day, 16 patient open label clinical trial of the drug delivery system continuously extruding LD-CD paste significantly reduces the variability of the plasma LD concentration and alleviates symptoms of advanced Parkinson's disease (PD) as compared to LD-CD tablets.

Topical Nanoliposomal Collagen Delivery for Targeted Fibril Formation by Electrical Stimulation.

Collagen is a complex, large protein molecule that presents a challenge in delivering it to the skin due to its size and intricate structure. However, conventional collagen delivery methods are either invasive or may affect the protein's structural integrity. This study introduces a novel approach involving the encapsulation of collagen monomers within zwitterionic nanoliposomes, termed Lip-Cols, and the controlled formation of collagen fibrils through electric fields (EF) stimulation. The results reveal the self-assembly process of Lip-Cols through electroporation and a pH gradient change uniquely triggered by EF, leading to the alignment and aggregation of Lip-Cols on the electrode interface. Notably, Lip-Cols exhibit the capability to direct the orientation of collagen fibrils within human dermal fibroblasts. In conjunction with EF, Lip-Cols can deliver collagen into the dermal layer and increase the collagen amount in the skin. The findings provide novel insights into the directed formation of collagen fibrils via electrical stimulation and the potential of Lip-Cols as a non-invasive drug delivery system for anti-aging applications.

Recent Excavation of Nanoethosomes in Current Drug Delivery.

In the current era, the Transdermal delivery of bioactive molecules has become an area of research interest. The transdermal route of administration enables direct entry of bioactive molecules into the systemic circulation with better and easy accessibility, bypassing the hepatic metabolism and improving patient compliance. Permeation through the skin has always been a barrier. To overcome this challenge, an efficient route by the vesicular system has been adopted so as to have better skin permeation of the bioactive molecules. A novel vesicular and non-invasive drug delivery system called Nanoethosomes was developed. Nanoethosomes are lipid-based vesicular carriers that are used for deeper permeation of the bioactive agents into the skin. The main components of Nanoethosomes are Phospholipids, water, and ethanol. High ethanol concentration in Nanoethosomes distinguishes them from other nano-formulation and results in deeper permeation and smaller vesicular size. This review article gives detailed information on the formulation techniques, and characterization parameters of nanoethosomes along with the research work done by various researchers in the same field. The compiled manuscript gives detailed elaboration about the various drugs used to treat different diseases which when incorporated in nanoethosomes resulted in better permeability and enhanced bioavailability.

Noninvasive Novel Transdermal Drug Delivery System for Deep Drug Permeability.

Noninvasive Novel Transdermal Drug Delivery System for Deep Drug Permeability.

Formulation and Characterization of Intranasal Drug Delivery of Frovatriptan-Loaded Binary Ethosomes Gel for Brain Targeting.

Frovatriptan succinate (FVT) is an effective medication used to treat migraines; however, available oral formulations suffer from low permeability; accordingly, several formulations of FVT were prepared. Prepare, optimize, and evaluate FVT-BE formulation to develop enhanced intranasal binary nano-ethosome gel.‎. Binary ethosomes were prepared using different concentrations of phospholipid PLH90, ethanol, propylene glycol, and cholesterol by thin film hydration and characterized by particle size, zeta potential, and entrapment efficiency. Furthermore, in-vitro, in-vivo, ex-vivo, pharmacokinetics, and histopathological studies were done. Regarding FVT-loaded BE, formula (F9) demonstrated the best parameters from the other formulas; with the lowest particle size (154.1±4.38‎ nm), lowest PDI (‎0.213±0.05), highest zeta potential (‎-46.94±1.05), and highest entrapment efficiency (89.34±2.37%). Regarding gel formulation, G2 showed the best gel formula with drug content (‎99.82±0.02‎%) and spreadability (12.88 g/cm2). In-vitro study results showed that, in the first 30 minutes, around 22.3% of the medication is released, whereas, after 24 hours, about 98.56% is released in G2. Based on enhancing the bioavailability and sustaining the drug release, it can be concluded that the Frovatriptan-Loaded Binary ethosome Gel as nano-delivery was developed as a promising non-invasive drug delivery system for treating migraine.

Buccal Patch: A New Avenue for Better Patient Compliance in Management of Diabetes Mellitus

Diabetes is a persistent metabolic condition that affects many individuals globally. To manage diabetes, patients need totake medication regularly, and the buccal patch has become a promising drug delivery option for this purpose. This review articlehighlights the potential of buccal patches as a novel approach to enhance patient compliance in treating diabetes mellitus. Byexploring the advantages of buccal patches as a non-invasive drug delivery system, this article emphasizes their potential to improvemedication adherence, thereby contributing to better management of diabetes mellitus. This article aims to evaluate the role ofbuccal patches in improving patient compliance in the treatment of diabetes mellitus. With the increasing global burden of diabetes,ensuring patient adherence to medication regimens is crucial for achieving optimal therapeutic outcomes. Traditional treatmentmethods often require frequent injections or oral administrations, which may lead to poor compliance due to various factors suchas fear of injections, inconvenience, or forgetfulness. Reviewing the literature on buccal patches as an alternative drug deliverysystem, this article explores their advantages in enhancing patient compliance. Buccal patches adhere to the inner lining of thecheek, providing a convenient and non-invasive route of drug administration. This approach eliminates the need for injections andreduces the frequency of oral medication intake, improving patient acceptance and adherence to treatment regimens. Furthermore,this article highlights the potential of buccal patches in delivering medications directly into the systemic circulation through thehighly vascularized oral mucosa. By bypassing first-pass metabolism in the liver, buccal patches can achieve higher drugconcentrations and improve therapeutic effects. Presenting the benefits of buccal patches for diabetes treatment encourages furtherresearch and development. So, the conclusion of this article is to promote awareness among healthcare professionals and patientsabout the potential of buccal patches as a patient-friendly approach to enhance compliance in the management of diabetes mellitus.

Improving antitumor targeting via using PL3 homing peptide and cell-penetrating peptide

Introduction: Tumor-homing peptides have gained great attention as tools for the development of non-invasive and targeting drug delivery systems (DDS) to minimize drug systemic toxicity and enhance bioavailability. This study aims to improve antitumor targeting in prostate cancer via uploading a drug to a DDS comprised of a cell penetrating peptide decorated with a tumor-homing peptide, PL3. Material and Methods: The DDS was constructed via solid-phase peptide synthesis and then characterized via mass spectrum and high performance liquid chromatography. A cell viability assessment to evaluate its cytotoxicity on both tumor (prostate cancer cells) and normal cells was conducted, while a confocal laser scanning microscope and flow-cytometer were employed to investigate internalization. To inspect the effectiveness of the drug-loaded DDS, a biochemical enzyme inhibition assay on the target enzyme dihydrofolate reductase (DHFR) was performed. ‎ Results and Discussion:‏ The findings supported the succeeded synthesis and loading of the drug into this carrier system and demonstrated its high efficacy in cytotoxic effect and inhibiting DHFR with considerable cellular uptake in prostate cancer cells. Conclusion: The drug was delivered to the target prostate cancer cells by the PL3-functionalized DDS, limiting its localization to tumor cells rather than normal cells. Therefore, the study results highlighted the significance of the DDS in tumor therapy interventions. Graphical Abstact

MICRONEEDLES ASSISTED ENHANCEMENT OF TRANSDERMAL DELIVERY OF CURCUMIN THROUGH ORGANOGEL FORMULATION

Curcumin is a natural compound found in turmeric and has been shown to have anti-inflammatory and antioxidant properties. Topical delivery of curcumin through an organic emulsion-based gel can effectively target inflammation at specific sites on the body. The current study aims to formulate Pluronic based organogel of curcumin, whose absorption is further assisted by microneedles technology. Nine organogel formulations were prepared and optimized by 32 full factorization model to fix the ratio of lecithin[A] and Pluronic[B] concentration in order to get optimum drug release after 2 hours (Q2) and maximum release of drug after 8 hours (Q8). The in-vitro study through the Franz diffusion cell indicated a significant impact of Pluronic F-127 concentration on the release of drug. As increased concentration of Pluronic increased the viscosity of formulations which ultimately retarded the release of drug. Based on Design of Experiment (DoE) study, optimized batch containing 6.5% lecithin and 20.6% Pluronic was further studied for microneedle assisted ex-vivo skin permeation through rat skin. Permeation without microneedle poration was around 70.26% after 8 hours, which was significantly increased (around 25%) after microneedle treatment of the skin. The results indicated promising application microneedle assisted skin permeation as a non-invasive and controlled delivery of curcumin through the transdermal route. Further, in-vivo studies are recommended to further establish this promising concept, targeting a variety of inflammatory conditions, including arthritis, psoriasis, and eczema, etc., through non-invasive transdermal drug delivery systems.

Sustained Release Microneedles: Materials and Applications in Facial Rejuvenation.

Wrinkled and loose skin resulting from collagen degradation along with fibers decreasing reflects the youth diminishing. Microneedles (MNs) have opened up new avenues for the development of painless and noninvasive transdermal drug delivery systems for facial rejuvenation. Encapsulated drugs or molecules are transmitted to targeted tissues via percutaneous microchannels, which eliminate potential gastric stimulation or first-pass metabolic effects, as well as boost patient compliance. Although MNs are considered effective and feasible therapeutic alternatives to metals, silicon, and polymers, traditional procedures with reduction processes continue to encounter methodological limitations. In recent years, promising additive manufacturing processes such as three-dimensional printing and two-photon polymerization manufacturing have been developed with the aim of overcoming the limitations by traditional processes to facilitate an efficient and economic production mode. This review summarizes the design, material selection, and manufacturing method for recently advanced MN systems. Furthermore, we also highlight specific polymeric or natural microneedle products, like hyaluronan, plant derivates, and vitamins, for esthetic applications in this review. Impact Statement In this review, the materials and manufactural routes of microneedles (MNs) are detailed. Moreover, similar to the diagnostic or therapeutic MNs, the feature of dispensation with training and ready-to-use is perfect for beautification and anti-aging, which necessitate repeated and long-term usage. Furthermore, the specific polymeric or natural products for esthetic applications of MNs are highlighted in this review.

Barrier-penetrating liposome targeted delivery of basic fibroblast growth factor for spinal cord injury repair.

Nanoparticle technologies offer a non-invasive means to deliver basic fibroblast growth factor (bFGF) for the treatment of spinal cord injury (SCI). However, the inability of bFGF to accumulate at the injury site and inefficient penetration across the blood-spinal cord barrier (BSCB) remain challenges. The present study describes a dual-targeting liposome (bFGF@Lip-Cp&Rp) with injury lesion targeting and BSCB-penetrating capability to deliver bFGF for SCI treatment. The CAQK peptide (Cp) with injury lesion targeting ability and R2KC peptide (Rp) with BSCB-penetrating capability were grafted onto the liposomes for a flexible and non-invasive drug delivery systems preparation. Results exhibit that the dual-targeted liposomes could significantly cross the BSCB and accumulate at the injury site. During the early stage of SCI, bFGF@Lip-Cp&Rp promotes repair of BSCB and facilitates M2-polarization of macrophages. Regular delivery of bFGF@Lip-Cp&Rp increase HUVECs tube formation and angiogenesis, ameliorate the microenvironment of lesion site, suppress the neuronal apoptosis and axonal atrophy in SCI rats. Importantly, continuous treatment of bFGF@Lip-Cp&Rp supports the restoration of limb motor function in SCI rats. In summary, this research implies that the injury site-targeting and BSCB-penetrating liposomes could be a promising therapeutic approach for the treatment of SCI.

Intranasal delivery of nanoliposomal SN-38 for treatment of diffuse midline glioma.

Diffuse midline gliomas, including diffuse intrinsic pontine gliomas (DIPGs), are among the most malignant and devastating childhood brain cancers. Despite aggressive treatment, nearly all children with these tumors succumb to their disease within 2 years of diagnosis. Due to the anatomical location of the tumors within the pons, surgery is not a treatment option, and distribution of most systematically administered drugs is limited by the blood-brain barrier (BBB). New drug delivery systems that bypass the BBB are desperately needed to improve outcomes of DIPG patients. Intranasal delivery (IND) is a practical and noninvasive drug delivery system that bypasses the BBB and delivers the drugs to the brain through the olfactory and trigeminal neural pathways. In this study, the authors evaluated the efficacy of nanoliposomal (LS) irinotecan (CPT-11) and an active metabolite of CPT-11, 7-ethyl-10-hydroxycamptothecin (SN-38), using IND in DIPG patient-derived xenograft models. In vitro responses to LS-CPT-11 and LS-SN-38 in DIPG cells were evaluated with cell viability, colony formation, and apoptosis assays. The cellular uptakes of rhodamine-PE (Rhod)-labeled LS-CPT-11 and LS-SN-38 were analyzed with fluorescence microscopy. Mice bearing DIPG patient-derived xenografts were treated with IND of LS-control (empty liposome), LS-CPT-11, or LS-SN-38 by IND for 4 weeks. In vivo responses were measured for tumor growth by serial bioluminescence imaging and animal subject survival. The concentration of SN-38 in the brainstem tumor administered by IND was determined by liquid chromatography-mass spectrometry (LC-MS). Immunohistochemical analyses of the proliferative and apoptotic responses of in vivo tumor cells were performed with Ki-67 and TUNEL staining. LS-SN-38 inhibited DIPG cell growth and colony formation and increased apoptosis, outperforming LS-CPT-11. Rhod-labeled LS-SN-38 showed intracellular fluorescence signals beginning at 30 minutes and peaking at 24 hours following treatment. LC-MS analysis revealed an SN-38 concentration in the brainstem tumor of 0.66 ± 0.25 ng/ml (5.43% ± 0.31% of serum concentration). IND of LS-SN-38 delayed tumor growth and significantly prolonged animal survival compared with IND of LS-control (p < 0.0001) and LS-CPT-11 (p = 0.003). IND of LS-SN-38 increased the number of TUNEL-positive cells and decreased the Ki-67-positive cells in the brainstem tumor. This study demonstrates that IND of LS-SN-38 bypasses the BBB and enables efficient and noninvasive drug delivery to the brainstem tumor, providing a promising therapeutic approach for treating DIPG.

Non-invasive drug delivery systems mediated by nanocarriers and molecular dynamics simulation for posterior eye disease therapeutics: Virtual screening, construction and comparison

Local deliver medication in a non-invasive pattern and attaining a long-term sustained release at ocular regions to minimize side effects is fascinating for treatment and precision medicine, but its rational design remains a challenge. The aim of this study was to analyze the effect of different delivery strategies on drug bioavailability in the posterior segment of the eye. In this study, the results of molecular dynamics (MD) revealed that quercetin (QUE) and curcumin (CUR) have shown superior affinity and tighter binding capacity for the active site of vascular endothelial growth factor (VEGF). Then, developing and comparing lipid-based nanoemulsion (NE) and polymer-based nanomicelles (NM) were modified with novel mPEG-CS to achieve adequate targeting and retention. The results of in vitro biological properties showed that nano-preparations could be successfully absorbed by cells. The result of in vivo pharmacokinetics revealed that two kinds of nano-preparations could prominently enhance the ocular bioavailability of QUE and CUR to different degrees and have a certain sustained-release effect. More importantly, the results showed that the particle size of NE was smaller than that of NM, which would make the drug retention time in the eye short and result in drug loss. Compared with NE, the release rate of NM was slower, and the effect of improving the drug bioavailability was more significant. In addition, the hydrophobic inner core-hydrophilic shell structure of NM and the carbonyl group in Soluplus material played a protective role in maintaining the stability of the drug. In summary, NM has a more significant effect on improving the ocular absorption of drugs, and is expected to become a candidate nanocarrier for non-invasive drug delivery systems and used for the treatment of post-ocular diseases.

Effect of Particulate Properties of Inhaled Dry Powder Formulation on Bioavailability, Dissolution Rate of Drug Particles and Rate of Drug Removal from the Body

Introduction: The use of pulmonary drug delivery as a non-invasive drug delivery system for the systemic treatment of diseases as well as the topical treatment of respiratory diseases is increasing. Among the various inhaled formulations, inhaled dry powders show advantages over the other forms of inhaled medicines due to high stability, bioavailability and ease of use. The effect of particle properties on the rate of drug delivery to the lungs in inhaled dry powders has been investigated in previous papers.&#x0D; Conclusion: Since the physicochemical properties of particles of dry powder inhalation formulations such as particle size, surface and particle shape, as well as the electrical charge of the particles play a decisive role in drug pharmacokinetics, in the present review article we intended to discuss the effect of these parameters of inhaled dry powder formulations on bioavailability, dissolution rate of drug particles and the rate of drug clearance from the body.

Polymeric nanoparticles in the diagnosis and treatment of myocardial infarction: Challenges and future prospects.

Myocardial infarction (MI) is the leading cause of morbidity and mortality worldwide. Despite extensive efforts to provide early diagnosis and adequate treatment regimens, detection of MI still faces major limitations and pathological MI complications continue to threaten the recovery of survivors. Polymeric nanoparticles (NPs) represent novel noninvasive drug delivery systems for the diagnosis and treatment of MI and subsequent prevention of fatal heart failure. In this review, we cover the recent advances in polymeric NP-based diagnostic and therapeutic approaches for MI and their application as multifunctional theranostic tools. We also discuss the in vivo behavior and toxicity profile of polymeric NPs, their application in noninvasive imaging, passive, and active drug delivery, and use in cardiac regenerative therapy. We conclude with the challenges faced with polymeric nanosystems and suggest future efforts needed for clinical translation.

Noninvasive Drug Delivery System Progress in Protein and Peptide Delivery

Protein and peptide drugs have tremendous therapeutic potential, and their usage in the treatment of various severe diseases has revolutionized the fields of pharmaceuticals and biotechnology. For successful therapeutic effects, several efforts have been made to deliver protein/peptide drugs through various routes of administration. Parenteral and nonparenteral drug deliveries are regarded as significant routes of drug absorption. However, there is a need to improve nonparenteral drug delivery systems (DDSs) through subsequent routes, including buccal, pulmonary, oral, ocular, transdermal, and nasal routes to increase drug absorption effectively. The study evaluated various DDS routes proposed for the distribution of proteins and peptides in terms of both parenteral and nonparenteral delivery systems. For this purpose, numerous research articles were searched from the year 2000 to 2021 using search engines such as PubMed, Google Scholar, Medline, ISI Web of Knowledge, and Bioline International while applying different keywords such as “protein and peptide drugs,” “drug delivery systems,” “parenteral and nonparenteral routes of drug delivery,” and “physicochemical barriers.” The invasive/parenteral routes have several limitations associated with drug delivery, such as poor patient compliance and the pain and discomfort associated with these routes inconvenience in treating the pediatric population. The oral route is one of the most convenient routes of noninvasive or nonparenteral drug administration; here, no pain and discomfort arise, thus helping in maintaining higher patient compliance or acceptance. The other routes of administration of proteins and peptides through buccal, intranasal, pulmonary, transdermal, rectal, and ocular routes have also been showing successful results. The success of the therapeutics is strongly influenced by the differential delivery of the targeted antigen, the choice of targeting protein or peptide, and the drug-release characteristics of the linker used. Furthermore, there should be an improvement in nonparenteral DDSs so that the drugs might be administered appropriately.

Simultaneous amelioration of diabetic ocular complications in lens and retinal tissues using a non-invasive drug delivery system

Topically administered delivery systems for ophthalmic applications have been studied for the treatment of anterior or posterior eye diseases. However, simultaneous treatment of both anterior and posterior eye diseases has not been explored. In this study, we fabricated a topically administrable polymeric nanoparticle (NP)- based delivery system consisting of pluronic®F-68 shell and polycaprolactone core for the simultaneous treatment of both anterior and posterior eye diseases. These NPs were loaded with pyrrolidine dithiocarbamate (PDTC) or triamcinolone acetonide (TA) separately. The drug loading in NPs was optimized to initially achieve a moderate burst release of PDTC followed by slow and sustained release of both PDTC and TA. The resultant delivery system was studied for its in vivo efficacy in a diabetic retinopathy (DR) and cataract rat model. The results demonstrated that administration of PDTC NPs + TA NPs minimized oxidative stress in lens as evidenced by reduced levels of protein carbonyls and malondialdehyde, and, ameliorated DR complications in retina as evidenced by reduced expression of hypoxia inducible factor-1α along with a reduction in number of neovascular tufts and acellular capillaries. Therefore, delivery of PDTC and TA using PCL-PF68 NPs could be a useful approach for simultaneous treatment of diabetic cataract and DR.

Bioengineered Biomimetic and Bioinspired Noninvasive Drug Delivery Systems

AbstractThe main purpose herein is to provide an up‐to‐date review on noninvasive biomimetic, bioinspired, and bioengineered drug delivery system (DDS). Noninvasive DDS is an ever‐growing field critical for the applicability of drugs. It offers noninvasive administration routes with improved controlled, targeted, and triggered drug delivery. Noninvasive DDS employ many approaches and strategies, such as, nano‐ and microparticles, lipid‐based systems, sonophoresis, electrophoresis and iontophoresis, penetration enhancers, microneedles, and gels. The last decade seen a surge in research papers employing the paradigms of biomimicry, bioinspiration, and bioengineering. However, since the use of these terms in noninvasive DDS field is often inconsistent and unclear, some generalized perspectives are provided on the possible usage of these terms in future publications. Additionally, a critical discussion on the novelty and origins of these paradigms is provided. The advantages and disadvantages of each of the noninvasive routes and their current main limitations are summarized. The main aspects of indicated fields are discussed: The unique physiology of the related tissues, the main hurdles for mass transport, the various DDS tested, and materials selection. Finally, the basic concepts and therapeutic effects of these DDS are discussed and future venues for noninvasive biomimetic, bioinspired, and bioengineered DDS research are proposed.

Cell penetrating peptide TAT-functionalized liposomes for efficient ophthalmic delivery of flurbiprofen: Penetration and its underlying mechanism, retention, anti-inflammation and biocompatibility

In treating eye diseases, topical administration on the ocular surface is the most convenient and acceptable route. However, the intraocular efficiency of non-invasive drug delivery systems is still considerably hampered by the eye’s defense barriers. In this work, cell-penetrating peptide TAT-functionalized, flurbiprofen-loaded liposomes (TAT-FB-Lip) were designed to enable transcorneal drug delivery and prolong ocular surface retention. The corneal penetration-promoting properties of TAT-functionalized liposomes (TAT-Lip) were confirmed in vitro using a corneal permeability assay and the HCE-T cell sphere model and in vivo by aqueous humor pharmacokinetics assessment. TAT-Lip induced an increase in intracellular calcium ion concentration and membrane potential depolarization. F-actin images of HCE-T cells treated with TAT-Lip show the tight junctions between cells partly opened. The cellular internalization pathway mainly depended on the electrostatic interaction between TAT-Lip and the cell membrane, and there is a certain degree of energy dependence. The pharmacokinetics of flurbiprofen in tears demonstrated TAT-Lip could reduce the drug loss rate. Moreover, the anti-inflammatory effect of TAT-FB-Lip was enhanced by markedly suppressing PGE2, IL-6, and TNF-α production in tears and aqueous humor in a rabbit conjunctivitis model. In conclusion, this work demonstrates that TAT-Lip is an effective ocular drug carrier system that facilitates transcorneal delivery.

NIR-responsive transdermal delivery of atenolol based on polyacrylamide-modified MoS2 nanoparticles

Transdermal drug delivery system (TDDS) is a successful non-invasive drug delivery system that shows several advantages. However, dose depletion effects remain a major challenge for sustained release TDDS. This study aimed to develop a polyacrylamide-modified MoS2 nanoparticles (CPAM-MoS2 NPs) based TDDS, which could control drug release and prolong the treatment time by light stimulation. In this work, the CPAM-MoS2 were produced by a facile hydrothermal method. The structure of CPAM-MoS2 NPs was detected by using FTIR, XRD and TEM, and the surface morphololgy of the NPs was observed by SEM. The colloid stability was tested by zeta potential and sedimentation volume ratio. Moreover, In vivo skin erythema study was conducted to explore the biocompatibility of CPAM-MoS2 NPs. As a result, the synthesisezed colloid-stable and skin-safe CPAM-MoS2 NPs possessed a high drug load efficiency of 87.2% and excellent photothermal conversion efficiency that was successfully applied in a TDDS with an enhancement ratio of 1.82. We measured its controlled release ability in an in vitro skin penetration test and, moreover, no drug depletion was observed during the 8-hour study in the light stimulation group. This paper describes the first use of CPAM-MoS2 NPs as a carrier for drugs in a TDDS.

Extraocular, periocular, and intraocular routes for sustained drug delivery for glaucoma.

Although once daily anti-glaucoma drug therapy is a current clinical reality, most therapies require multiple dosing and there is an unmet need to develop convenient, safe, and effective sustained release drug delivery systems for long-term treatment to improve patient adherence and outcomes. One of the first sustained release drug delivery systems was approved for the reduction of intraocular pressure in glaucoma patients. It is a polymeric reservoir-type insert delivery system, Ocusert™, placed under the eyelid and on the ocular surface for zero-order drug release over one week. The insert, marketed in two strengths, released pilocarpine on the eye surface. While many clinicians appreciated this drug product, it was eventually discontinued. No similar sustained release non-invasive drug delivery system has made it to the market to date for treating glaucoma. Drug delivery systems under development include punctal plugs, ring-type systems, contact lenses, implants, microspheres, nanospheres, gels, and other depot systems placed in the extraocular, periocular, or intraocular regions including intracameral, supraciliary, and intravitreal spaces. This article discusses the advantages and disadvantages of the various routes of administration and delivery systems for sustained glaucoma therapy. It also provides the reader with some examples and discussion of drug delivery systems that could potentially be applied for glaucoma treatment. Interestingly, one intracamerally injected implant, Durysta™, was approved recently for sustained intraocular pressure reduction. However, long-term acceptance of such devices has yet to be established. The ultimate success of the delivery system will depend on efficacy relative to eye drop dosing, safety, reimbursement options, and patient acceptance. Cautious development efforts are warranted considering prior failed approaches for sustained glaucoma drug delivery. Neuroprotective approaches for glaucoma therapy including cell, gene, protein, and drug-combination therapies, mostly administered intravitreally, are also rapidly progressing towards assessment in humans.