Topical Drug Delivery Systems Research Articles

Anti-Cancer Nanofibrous Bandage Based on PVA Nanofibers Loaded with Gefitinib for Skin Cancer Treatment

Cancer is one of the leading causes of death worldwide, requiring sophisticated and versatile treatment options. As the enabling concept, nanotechnology has emerged to improve the efficacy of the current treatment strategies and eliminate their shortcomings and limitations. Accordingly, the main purpose of the current study is to develop a topical drug delivery system for Gefitinib (Gef), an EGFR inhibitor, based on the electrospun nanofibers. Electrospinning was applied to fabricate PVA nanofibers with different concentrations of Gef, 5, 7.5, and 10 wt.%, and the SEM imaging showed that the nanofibers were straight, uniform, and beadles. The results showed that adding Gef did not significantly compromise the mechanical strength of nanofibers. The fabricated anticancer nanofibrous bandage exhibited a burst drug release following a sustained release profile. The cell lethality assay revealed that the treatment of the cells with the Gef-loaded nanofibers induced dose-dependent toxicity, which is valuable for the intended anticancer application. The results of the present study showed that Gef can be loaded into PVA nanofibers without disrupting the morphology and mechanical properties of the nanofibers and can be applied as topical drug delivery for skin cancer.

Fabrication, In Vitro, and In Vivo Assessment of Eucalyptol-Loaded Nanoemulgel as a Novel Paradigm for Wound Healing.

Wounds are the most common causes of mortality all over the world. Topical drug delivery systems are more efficient in treating wounds as compared to oral delivery systems because they bypass the disadvantages of the oral route. The aim of the present study was to formulate and evaluate in vitro in vivo nanoemulgels loaded with eucalyptol for wound healing. Nanoemulsions were prepared using the solvent emulsification diffusion method by mixing an aqueous phase and an oil phase, and a nanoemulgel was then fabricated by mixing nanoemulsions with a gelling agent (Carbopol 940) in a 1:1 ratio. The nanoemulgels were evaluated regarding stability, homogeneity, pH, viscosity, Fourier-transform infrared spectroscopy (FTIR), droplet size, zeta potential, polydispersity index (PDI), spreadability, drug content, in vitro drug release, and in vivo study. The optimized formulation, F5, exhibited pH values between 5 and 6, with no significant variations at different temperatures, and acceptable homogeneity and spreadability. F5 had a droplet size of 139 ± 5.8 nm, with a low polydispersity index. FTIR studies showed the compatibility of the drug with the excipients. The drug content of F5 was 94.81%. The percentage of wound contraction of the experimental, standard, and control groups were 100% ± 0.015, 98.170% ± 0.749, and 70.846% ± 0.830, respectively. Statistically, the experimental group showed a significant difference (p < 0.03) from the other two groups. The results suggest that the formulated optimized dosage showed optimum stability, and it can be considered an effective wound healing alternative.

Skin permeability prediction with MD simulation sampling spatial and alchemical reaction coordinates

A molecular-level understanding of skin permeation may rationalize and streamline product development, and improve quality and control, of transdermal and topical drug delivery systems. It may also facilitate toxicity and safety assessment of cosmetics and skin care products. Here, we present new molecular dynamics simulation approaches that make it possible to efficiently sample the free energy and local diffusion coefficient across the skin’s barrier structure to predict skin permeability and the effects of chemical penetration enhancers. In particular, we introduce a new approach to use two-dimensional reaction coordinates in the accelerated weight histogram method, where we combine sampling along spatial coordinates with an alchemical perturbation virtual coordinate. We present predicted properties for 20 permeants, and demonstrate how our approach improves correlation with ex vivo/in vitro skin permeation data. For the compounds included in this study, the obtained log KPexp-calc mean square difference was 0.9 cm2 h−2.

The next generation of sinus stents for chronic rhinosinusitis: A systematic review

Characterized by impaired mucociliary clearance with subsequent compromised microbial elimination, chronic rhinosinusitis (CRS) is known as a multifactorial disease process in which bacterial infection or colonization could play a role in the initiation or propagation of the inflammatory response. Various non-systemic, topical therapies have recently emerged as an alternative to conventional oral regimens in managing CRS. A topical sinonasal drug delivery system using a bioabsorbable stent represents one of the most attractive methods among multiple topical delivery options. This review discusses the commercially available topical drug delivery platform (sinus stents) for CRS and its shortcomings. Based on the current drawbacks of sinus stents, this article has also highlighted the future developmental perspectives to create the next generation of a sinus stent, thereby harnessing the full potential of the sinus stent as efficient topical drug delivery for recalcitrant CRS.

Recent advances and future prospective of topical and transdermal delivery systems

Recent advances in topical and transdermal drug delivery systems have enabled targeted delivery of therapeutics to the site of action by enhancing drug permeation across the stratum corneum and increased bioavailability. Despite various technological advancements, some dermatoses still have limited treatment options due to potential adverse effects and challenges in formulation development. To address some of the limitations posed by conventional dermatotherapy, nano-based technologies have been developed and have demonstrated a significant improvement in dermatotherapy. Their distinct physicochemical properties demonstrate their overall superior therapeutic efficacy in providing sustained and effective targeted drug release, as well as improved solubility of hydrophobic actives with optimized drug formulations. These nanocarriers are commonly classified as polymeric, lipid-based, metallic, and vesicular nanocarriers, including nanoemulsions, nanofibers, and microneedles. This mini-review aims to address recent advances in nano-based technologies, providing a brief insight on some of the current and prospective technologies and approaches aimed at improving transdermal delivery.

Polyaphron Dispersion Technology, A Novel Topical Formulation and Delivery System Combining Drug Penetration, Local Tolerability and Convenience of Application.

Topical formulation and delivery technologies for pharmaceutical application should simultaneously address efficacy, safety and convenience of therapy. This has historically proven to be challenging, since formulation features that drive efficacy often have undesirable consequences for safety and convenience and vice versa. Polyaphron dispersion (PAD) technology is a novel topical formulation and drug delivery system developed with the purpose of preserving these key attributes. PAD formulations are typically oil-in-water dispersions consisting of oil droplets encapsulated in a multi-molecular shell structure. This shell structure protects potentially unstable active molecules solubilized in the oil from hydrolytic degradation. Example data are presented of enhanced drug penetration from PAD formulations, including dermal delivery of calcipotriene, betamethasone dipropionate and tacrolimus as well as ocular delivery of ciclosporin A. Local tolerability is an important safety parameter for topical formulations, where high levels of surfactants can cause skin irritation. In this regard, a key benefit of PAD formulations is the inherent reduced requirement for surfactants to generate stable formulations compared to conventional emulsion systems. Patients with chronic diseases with topical manifestations such as psoriasis or atopic dermatitis have been reported to miss up to 70% of planned topical applications, mainly due to a lack of satisfaction with their therapy. Patients generally prefer light, moisturizing, non-greasy and quickly absorbed vehicles that are simple to use on all body parts. PAD formulations can generally be designed to meet these criteria. In conclusion, PAD technology provides high flexibility in topical drug design and can be applied to several body locations without compromising efficacy, safety or convenience of therapy.Clinical Trial Register: Clinicaltrials.gov: NCT03802344.

Sustained Release of Tacrolimus From a Topical Drug Delivery System Promotes Corneal Reinnervation.

PurposeCorneal nerve fibers provide sensation and maintain the epithelial renewal process. Insufficient corneal innervation can cause neurotrophic keratopathy. Here, topically delivered tacrolimus is evaluated for its therapeutic potential to promote corneal reinnervation in rats.MethodsA compartmentalized neuronal cell culture was used to determine the effect of locally delivered tacrolimus on sensory axon regeneration in vitro. The regenerating axons but not the cell bodies were exposed to tacrolimus (50 ng/mL), nerve growth factor (50 ng/mL), or a vehicle control. Axon area and length were measured after 48 hours. Then, a biodegradable nanofiber drug delivery system was fabricated via electrospinning of a tacrolimus-loaded polycarbonate–urethane polymer. Biocompatibility, degradation, drug biodistribution, and therapeutic effectiveness were tested in a rat model of neurotrophic keratopathy induced by stereotactic trigeminal nerve ablation.ResultsSensory neurons whose axons were exposed to tacrolimus regenerated significantly more and longer axons compared to vehicle-treated cultures. Trigeminal nerve ablation in rats reliably induced corneal denervation. Four weeks after denervation, rats that had received tacrolimus topically showed similar limbal innervation but a significantly higher nerve fiber density in the center of the cornea compared to the non-treated control. Topically applied tacrolimus was detectable in the ipsilateral vitreal body, the plasma, and the ipsilateral trigeminal ganglion but not in their contralateral counterparts and vital organs after 4 weeks of topical release.ConclusionsLocally delivered tacrolimus promotes axonal regeneration in vitro and corneal reinnervation in vivo with minimal systemic drug exposure.Translational RelevanceTopically applied tacrolimus may provide a readily translatable approach to promote corneal reinnervation.

Formulation and evaluation of posaconazole loaded nanostructured lipid carriers for topical drug delivery system

The aim of the present study was to formulate and evaluate Posaconazole loaded NLCs gel using solid lipid as GMS, liquid lipid as oleic acid and surfactants as tween 80 and span 80, with the help of high-speed homogenization followed by sonication technique to improve the bioavailability, to avoid the oral side effects, to achieve the site-specific delivery and to improve the patient compliance. NLCs of Posaconazole was prepared with different drug: carrier ratios using high speed homogenization followed by sonication technique. % entrapment efficiency for F3 batch of NLC was found to be more than 95%. SEM studies were carried out and depending on it F3 batch was found to have particle size range 200nm which was selected as optimized NLCs batch. IR, XRD and DSC were performed to identify the physicochemical interaction between drug and optimized formulation. The optimized NLCs was then incorporated into gel base to form Posaconazole loaded NLCs gel. The prepared NLCs gel were evaluated for viscosity, pH, spread-ability, extrudability and in-vitro drug release studies. It was found to be 34666 cps, 5.7, 12.22 ±0.8 cm, 85.34% and drug release of NLCs gel within 6hrs was 98.62% respectively. The obtained data for in-vitro drug release was putted in various mathematical kinetic models. Hence, F3 batch was selected as optimized batch.

Optimization of Oxiconazole Topical Emulgel Formulation for the Treatment of Skin Infections

Emulgel is one of the promising topical drug delivery system for the delivery of hydrophobic drugs which overcome a variety of disadvantages of ointments and creams like greasiness as well as phase inversion. The aim of present work was to develop and evaluate Oxiconazole emulgel. Oxiconazole emulgel was prepared by using polymers like Carbopol 934 and HPMC K4M at different concentrations. Oxiconazole is a broad spectrum anti - fungal agent used in treat of various skin infections such as athlete’s foot, jock itch and ring worm. The prepared emulgels were evaluated in terms of physical appearance, measurement of pH, viscosity, spreadability, drug content and in vitro diffusion studies and skin irritation study. Formulation F1 containing carbapol 934 is considered as optimized formulation because it showed highest drug release i.e., 58.57% in 8 hrs.

Antibiotic Emulgel: Design and Characterization for Topical Drug Delivery

Objectives: The benefits of topical drug delivery systems, which have been used for centuries, include the ability to deliver medications both quickly to the affected area where they are most effective and over an extended period of time. These systems lengthen the drug's mean resident time and contact time. The design and characterization of an antibiotic emulgel for topical medication administration is a goal of the current investigation. Methods: Cefpodoxime Proxetil emulgel were prepared using different concentration of Carbopol 934, HPMC K4M and xanthan gum as gelling agents and evaluated the relevant parameters such as physical examinations, pH, extrudability, spreadability, viscosity, swelling index, drug content, in-vitro diffusion studies and microbiology activities. Results: All formulations are neutral and viscosity of emulgel was found in the acceptable limits. On physical evaluations were found to be optimum in terms spreadability, swelling index and extrudability. Drug content of all formulations were found in the ranges 69.73% to 97.58% and CEF4 emulgel exhibiting the highest drug concentration and the lowest percentage drug release due to its controlled release pattern and proven non-fickian diffusion mechanism release. The results found that, the selected formulations proven better bacterial activities against both gram positive and gram negative organisms. Conclusions: Type and concentration of polymers can have an impact on the drug permeability studies and physical-chemical characteristics of the developed antibiotic emulgel, which had excellent results and was suitable for possible therapeutic purposes.

Development and characterization of the electrospun melittin-loaded chitosan nanofibers for treatment of acne vulgaris in animal model

Acne is an inflammatory disease of the sebaceous glands. Melittin (Mel) is one of the principal toxic components of bee venom that can cause antibacterial and anti-inflammatory effects. Chitosan is a biodegradable polysaccharide has anti-inflammatory, antimicrobial, and regenerative properties. In this study, chitosan (Ch)/Mel 0.001 and 0.003% nanofibers were fabricated for topical treatment of acne vulgaris. Physicochemical properties of Ch/Mel were evaluated using FTIR and FESEM. Furthermore, encapsulation efficiency, tensile strength, water absorption capacity, enzymatic activity, drug release, antimicrobial, and cell cytotoxicity were assayed. Animal models were exerted to study the impact of Ch/Mel nanofibers on the treatment of Propionibacterium acnes. The FESEM results showed that nanofibers were successfully prepared in nano-scale fiber diameter. The FTIR confirmed the presence of Mel in structures. The addition of melittin to the polymer solution reduced electrical conductivity, induced viscosity and tensile strength of the fibers, and decreased the percentage of the swelling. The Mel loading into Ch/Mel 0.003% was reported at 86.74±1%. This Mel releasing process (89.65%) of Ch/Mel 0.003% was slowly completed during 72 h. The Mel retained its hemolytic activity after being loaded into the polymer structure. The drug toxicity study displayed the lack of any significant toxicity from Ch/Mel nanofibers on normal Human Dermal Fibroblasts (HDF). The Ch/Mel 0.003% achieved the highest growth inhibition in P. acnes in vitro and animal studies, this group showed the greatest reduction in inflammation and redness. The Ch/Mel 0.003% structure is proposed as a suitable topical drug delivery system for treating acne vulgaris.

Evaluation of wound-healing efficiency of a functional Chitosan/Aloe vera hydrogel on the improvement of re-epithelialization in full thickness wound model of rat

ObjectiveChitosan-based hydrogels as wound dressings are expected to improve the efficiency of the wound-healing process. Fabrication of the composite structure of Aloe vera and biopolymeric hydrogels has been demonstrated to promote the wound-healing process through protection against a wide spectrum of microbes, and enhanced cell adhesion and differentiation. Therefore, the present study investigates to development of improved CHO/Aloe hydrogel for improving the wound-healing process in an animal model. Materials and methodsCHO hydrogel with Aloe was prepared, and its properties were evaluated in terms of viscosity, antibacterial activity, and ints In-vivo wound-healing efficiency in full-thickness wounds of rat models. Physical examination of wound-healing efficiency of CHO/Aleo hydrogel was evaluated by analyzing total wound closure, recovery percentage, and the epiderm thickness of wounds. Histological evaluation was performed using hematoxylin and eosin staining to evaluate the re-epithelialization, inflammatory response, granulation tissue formation, and fibrotic tissue formation. ResultsThe results showed a significantly higher wound-healing rate of the CHO/Aleo group compared to other groups at 3,7,14 days (p < 0.05). After 14 days of treatment, the best healing effect was observed in the CHO/Aleo gel with the highest tissue tension compared with other groups (p < 0.05). Histological findings indicated a significant difference in inflammatory response between control and treatment groups after three days of treatment (p < 0.05). Epidermal thickness was also significantly thicker in the CHO/Aleo gel group than others (p < 0.05). ConclusionThe present study an improved the effective topical drug-delivery system by CHO/Aloe hydrogel with the potential to reduce inflammation over time, allowing the body to recover more quickly and better re-epithelialization for improving the wound-healing procedures.

Microsponge: An adaptable topical drug delivery system

Microsponge: An adaptable topical drug delivery system

Microsponge: An adaptable topical drug delivery system

Microsponge a drug delivery system, possesses the versatility to load a wide range of active ingredients due large surface area. it facilitates controlled release of active ingredients and reduces systemic exposure and adverse effect. microsponges are polymeric sponges that consist of interconnecting voids with a flexible structure with a porous surface. Microsponge delivery techniques provides extended product stability, enhanced safety, enhanced formulation flexibility, product efficacy and aesthetic appeal with reduced adverse effects. It is regarded as safe, due to less bacterial contamination as it doesn’t require preservatives in the formulation. Therefore it is used in various sterile formulations like ophthalmic, parenteral etc. This review provides an overview of microsponge technology with its methodology, mechanism, programmable release, characterization and recent data on marketed formulations, their applications, and the list of patents, evaluation and application of microsponges in various aspects. Microsponge are frequently used for topical application but recently used for oral also.

Capsanthin from Capsicum annum fruits exerts anti-glaucoma, antioxidant, anti-inflammatory activity, and corneal pro-inflammatory cytokine gene expression in a benzalkonium chloride-induced rat dry eye model.

Dry eye disease (DED) is a complex ocular surface inflammatory disease. Its occurrence varies widely over the world, ranging from 5% to 34%. The use of preservatives, specifically benzalkonium chloride, in the ocular drops worsens the DED conditions. Furthermore, the Covid-19 pandemic increased screen time and the use of face masks and shields. As a result, the number of people suffering from dry eye disease (DED) has increased significantly in recent years. The main objective of our study is to find a solution to manage the dry eye disease (DED) preferably from natural source without any adverse events. In this study, the beneficial effects of capsanthin from Capsicum annum (CCA) were evaluated on benzalkonium chloride (BAC)-induced dry eye disease (DED) in Albino Wistar rats. Oral supplementation of CCA resulted in a statistically significant decrease in intraocular pressure (IOP) (p < .0001), increase in tear break-up time (TBUT) (p < .01), decline in Schirmer test results (p < .01), and decrease in corneal surface inflammation (p < .01). Capsanthin ameliorated in reducing oxidative stress by increasing serum antioxidant levels such as glutathione peroxidase (GPX), nitric oxide (NO), and lactoferrin (LTF) and inhibiting matrix metalloproteinases 2 and 9 (MMP2 and MMP9) (p < .0001). Capsanthin treatment significantly inhibited the expression of inflammatory cytokines, tumor necrosis factor-alpha (TNF-α), interleukins (IL-2, IL-4, IL-6), and pro-inflammatory mediator, matrix metalloproteinase-9 (MMP9). Furthermore, the lacrimal gland expressed vascular cell adhesion molecule (VCAM-1), and prostaglandin-endoperoxide synthase 2 (PTGS2) was suppressed by CCA treatment. PRACTICAL APPLICATIONS: Benzalkonium chloride (BAC), a preservative widely used in the topical ocular drug delivery system (ODDS), causes undesirable effects such as dry eye disease as well as ameliorating intraocular pressure leading to optical nerve damage and irreversible vision loss. Capsanthin from Capsicum annum (CCA) can be used to treat symptoms related to dry eye disease such as inflammation, eye irritation, visual disturbance, ocular discomfort with potential damage to the ocular surface. The CCA may be beneficial in the treatment of glaucoma, an elevated intraocular pressure. Capsanthin from C.annum can be useful in managing DED by increasing tear break-up time (TBUT), declining in Schirmer test results and decreasing in corneal surface inflammation.

Emulgel: A revolution in topical drug delivery system

Topical delivery of drugs is one of the ideal routes of administrating a wide range of drug candidates and emulgels are emerging as a novel formulation, which exhibited the characteristics of both the emulsions and gels. Emulgel demonstrated improved penetrability during several studies and it is able to deliver hydrophilic as well as hydrophobic drugs and hence overcome the limitations of traditionally available topical preparations. More stable and effective emulgels can be prepared by nanonizing and micronizing the globules of emulsions, which improves the stability and half-life of Emulgels. The commercial availability along with the presence of strong clinical pipeline of emulgels is indicating towards the acceptance of this formulation while several advantages associated with this approach is also suggesting towards its potential as ideal topical drug delivery system. This article enlisted in-depth information about the emulgels, its components and structure along with the general method of production, evaluation and future scenario of this approach. The article also involved information about the patents insight, commercially available products and previously used drugs for developing stable emulgels.

Emulgel

Topical delivery of drugs is one of the ideal routes of administrating a wide range of drug candidates and emulgels are emerging as a novel formulation, which exhibited the characteristics of both the emulsions and gels. Emulgel demonstrated improved penetrability during several studies and it is able to deliver hydrophilic as well as hydrophobic drugs and hence overcome the limitations of traditionally available topical preparations. More stable and effective emulgels can be prepared by nanonizing and micronizing the globules of emulsions, which improves the stability and half-life of Emulgels. The commercial availability along with the presence of strong clinical pipeline of emulgels is indicating towards the acceptance of this formulation while several advantages associated with this approach is also suggesting towards its potential as ideal topical drug delivery system. This article enlisted in-depth information about the emulgels, its components and structure along with the general method of production, evaluation and future scenario of this approach. The article also involved information about the patents insight, commercially available products and previously used drugs for developing stable emulgels.

Formulation development, in vitro and in vivo assessment of Diclofenac diethylamine nanosponge loaded topical formulation

The present work was performed with the objective of novel topical formulation development of poorly water-soluble drug Diclofenac diethylamine by loading the drug-containing nanosponge into the topical formulation. The nanosponges are polymeric nanoparticles that entrap the drug. The drug-loaded nanosponge has different absorption characteristics in comparison to the pure drug in the topical drug delivery system. Methods: The drug was first loaded in the ethylcellulose nanosponge using the emulsion solvent diffusion method. Then Diclofenac diethylamine nanosponge-loaded topical gel formulations were developed by using Carbopol 940 as a gel-forming polymer. Result: The Diclofenac diethylamine-loaded nanosponges were evaluated for various evaluation parameters such as particle size distribution, surface morphology, drug entrapment efficiency, polydispersity index, etc. The topical gel formulations were evaluated for pH, in vitro drug release, viscosity, in vivo performance and compared with the marketed formulation. The average size of prepared nanosponge formulations was found in the range of 102.8 nm to 475.5 nm. Scanning electron microscopy photographs of developed formulations reveal the spongy and porous nature of particles along with spherical shape. The polydispersity index (PI) was found in the range of 0.756 to 0.954.

A Systemic Review on Micro-emulsion: Liquid Dosage form for Topical Drug Delivery System

Microemulsions (ME) is a system that combines water, oil, and an emulsifier / surfactant which is a form of volatile liquid, homogeneous and kinetically stable. Microemulsion is an attractive drug delivery system for topical administration. Due to its solubility, mild skin irritation, and watery swelling are used in the Topical Drug Delivery System (TDDS). By improving the quality of skin texture, it provides a level of penetration. The function of skin balance is to limit the penetration of bacteria, viruses, and other environmental factors. With standard drugs, skin penetration may take time and have not been able to provide immediate action. So, in this case, we used the Microemulsion-based Topical Drug Delivery system. Microemulsion increases solubility, protects the drug from environmental factors and improves drug bioavailability. MEs provide high penetration and the ability to penetrate into the skin. Because of this, the immediate action of the drug can occur in the infected area. Due to the presence of a hydrophilic and lipophilic environment, it provides outstanding biocompatibility. There are several test frames used to maintain stability, microemulsion kinetics.

Luliconazole Nail Lacquer for the Treatment of Onychomycosis: Formulation, Characterization and In Vitro and Ex Vivo Evaluation.

Onychomycosis is the most common fungal infection of the nail affecting the skin under the fingertips and the toes. Currently, available therapy for onychomycosis includes oral and topical therapies, either alone or in combination. Oral antifungal medication has been associated with poor drug bioavailability and potential gastrointestinal and systemic side effects. The objective of this study was to prepare and evaluate the luliconazole nail lacquer (LCZ-NL) for the effective treatment of onychomycosis. In the current work, LCZ-NL was formulated in combination with penetration enhancers to overcome poor penetration. A 32 full factorial formulation design of experiment (DOE) was applied for optimization of batches with consideration of dependent (drying time, viscosity, and rate of drug diffusion) and independent (solvent ratio and film former ratio) variables. The optimized formulation was selected based on drying time, viscosity, and rate of drug diffusion. The optimized formulation was further evaluated for % non-volatile content assay, smoothness of flow, water resistance, drug content, scanning electron microscope (SEM), atomic force microscope (AFM), X-ray diffraction (XRD), differential scanning calorimetry (DSC), in vitro drug release, ex vivo transungual permeation, antifungal efficacy, and stability study. The optimized LCZ-NL contained 70:30 solvent ratio and 1:1 film former ratio and was found to have ~ 1.79-fold higher rate of drug diffusion in comparison with LULY™. DSC and XRD studies confirmed that luliconazole retains its crystalline property in the prepared formulation. Antifungal study against Trichophyton spp. showed that LCZ-NL has comparatively higher growth inhibition than LULY™. Hence, developed LCZ-NL can be a promising topical drug delivery system for treating onychomycosis.