Dissolving Microneedles Patch: A Promising Approach for Advancing Transdermal Delivery of Antischizophrenic Drug.

OBJECTIVE: Microneedles (MNs) are minimally invasive transdermal drug delivery systems capable of penetrating the stratum corneum to overcome the barrier properties. The primary objective of this research was to prepare dissolving microneedle patches (DMNP) loaded with quetiapine (QTP). METHODS: DMNP were fabricated employing the solvent casting technique, utilizing various polymer feed ratios including polyvinyl alcohol (PVA), polyvinylpyrrolidone K30 (PVP-K30), and polylactide-co-glycolide (PLGA) polymers. The loaded DMNP with QTP underwent a comprehensive characterization process encompassing assessments for compatibility, thickness, insertion potential, morphology, thermal behavior, X-ray diffraction, ex-vivo permeation, skin irritation, and histopathological changes. RESULTS: FTIR studies confirmed the compatibility of QTP with the microneedle patch composites. The thickness of the drug-loaded DMNP ranged from 0.67 mm to 0.97 mm. These microneedles exhibited an impressive penetration depth of 480 µm, with over 80% of the needles maintaining their original shape after piercing Parafilm-M. SEM analysis of the optimized DMNP-2 revealed the formation of sharp-tipped and uniformly surfaced needles, measuring 570 µm in length. Remarkably, the microneedles did not elicit any signs of irritation upon application of the prepared DMNP. The DMNP-2 showcased an impressive cumulative ex-vivo permeation of QTP, reaching 17.82 µg/cm2/hr. Additionally, histopathological assessment of vital organs in rabbits attested to the safety profile of the formulated microneedle patches. CONCLUSIONS: In conclusion, the developed microneedle patch represents a promising strategy for enhancing the transdermal delivery of QTP. This innovative approach has the potential to increase patient compliance, offering a more efficient and patient-friendly method of administering QTP.

In Vivo Evaluation of Miconazole-Nitrate-Loaded Transethosomal Gel Using a Rat Model Infected with Candida albicans.

Miconazole nitrate (MCNR), an antifungal drug, is used to treat superficial infections. The objective of the current study was to assess the antifungal effectiveness of MCNR-loaded transethosomal gel (MNTG) against Candida albicans in an in vivo rat model. The outcomes were compared with those of the miconazole nitrate gel (MNG) and marketed Daktarin® cream (2%) based on histopathological and hematological studies. The results of the skin irritation test revealed the safety profile of the MNTG. The MNTG demonstrated the greatest antifungal activity in the histological analysis and the visible restoration of the skin, and the rats revealed an apparent evidence of recovery. Compared to the untreated group, the treated group's lymphocyte and white blood cells counts increased, but their eosinophil counts decreased. In conclusion, MNTG exhibited the greatest antifungal activity, which might be connected to the improved skin permeability of the transethosome's nanosized vesicles. Therefore, it could be considered a promising carrier for topical usage and the treatment of cutaneous candidiasis. More clinical research needs to be performed in order to demonstrate its effectiveness and safe usage in humans.

Compritol®-based solid lipid nanoparticles of desvenlafaxine prepared by ultrasonication-assisted hot-melt encapsulation to modify its release.

Aims: Desvenlafaxine (DES) in conventional dosage forms shows initial burst release after oral administration, leading to exaggeration of its side effects. These side effects can be overcome by a sustained-release dosage form using the chemically inert, low-melting-point lipid Compritol® 888 ATO, as it reduces initial burst release. Materials & methods: The potential of DES-loaded solid lipid nanoparticles (DES-SLNs) synthesized by ultrasonication-assisted hot-melt encapsulation to modify the release of DES was investigated. Results: The entrapment efficiency of DES-SLNs was 65.90% with the in vitro release profile showing a sustained-release behavior achieving 81% cumulative release within 16 h without initial burst release. Conclusion: DES-SLNs are a potential carrier for sustained release of water-soluble antidepressant drugs such as DES.

[Box: see text].

Old drug, new tricks: polymer-based nanoscale systems for effective cytarabine delivery.

Cytarabine, an antimetabolite antineoplastic agent, has been utilized to treat various cancers. However, because of its short half-life, low stability, and limited bioavailability, achieving an optimal plasma concentration requires continuous intravenous administration, which can lead to toxicity in normal cells and tissues. Addressing these limitations is crucial to optimize the therapeutic efficacy of cytarabine while minimizing its adverse effects. The use of novel drug delivery systems, such as polymer-based nanocarriers have emerged as promising vehicles for targeted drug delivery due to their unique properties, including high stability, biocompatibility, and tunable release kinetics. In this review, we examine the application of various polymer-based nanocarriers, including polymeric nanoparticles, polymeric micelles, dendrimers, polymer-drug conjugates, and nano-hydrogels, for the delivery of cytarabine. The article highlights the limitations of conventional cytarabine administration which often lead to suboptimal therapeutic outcomes and systemic toxicity. The rationale for using polymer-based nanocarriers is discussed, highlighting their ability to overcome challenges by providing controlled drug release, improved stability, and enhanced targeting capabilities. In summary, this review offers a valuable resource for drug delivery scientists by providing insights into the design principles, formulation strategies, and potential applications of polymer-based nanocarriers that can enhance the therapeutic efficacy of cytarabine.

Development and in-vitro evaluation of chitosan and glyceryl monostearate based matrix lipid polymer hybrid nanoparticles (LPHNPs) for oral delivery of itraconazole.

Itraconazole (ICZ) is a broad spectrum antifungal drug, but used as second or third line therapy due to its low and erratic oral bioavailability. This work was carried out to prepare and characterize matrix type lipid-polymer hybrid nanoparticles (LPHNPs) for dissolution enhancement of ICZ. LPHNPs were prepared using solvent diffusion/emulsification technique. Matrix LPHNPs were composed of chitosan (polymer), glyceryl monostearate (lipid) and poloxamer 188 (stabilizer). LPHNPs loaded with ICZ (LPHNPs-1, LPHNPs-2, LPHNPs-3 and LPHNPs-4) were developed using varying concentration of chitosan whereas LPHNPs (LPHNPs-5, LPHNPs-6, LPHNPs-7 and LPHNPs-8) were prepared using varying concentrations of poloxamer 188. LPHNPs loaded with ICZ were further evaluated for entrapment efficiency, particle size, polydispersity index (PDI), zeta potential and dissolution profiles at biorelevant pH conditions. The particle size (LPHNPs-1 to LPHNPs-4) was found to be in range of 421-588 nm with PDI values 0.34-0.41. The particles size of LPHNPs-5 to LPHNPs-8 was found to be in range of 489-725 nm with PDI 0.34-0.74. The entrapment efficiency of LPHNPs-1 to LPHNPs-4 was found to be in range of 85.21%-91.34%. The entrapment efficiency of LPHNPs-5 to LPHNPs-8 was found to be in range 78.32%-90.44%. . The scanning electron microscopy of optimized formulations LPHNPs-1 and LPHNPs-5 indicated formation of oval shaped nanoparticles. DSC thermogram of ICZ loaded LPHNPs also depicted the conversion of crystalline form of ICZ into amorphous form demonstrating the internalization and dissolution enhancement of drug in the hybrid matrix. The cumulative drug dissolved at acidic pH 1.2 was found to be 23.3% and 19.8% for LPHNPs-1 and LPHNPs-5 respectively. Similarly at basic pH values 7.4, cumulative amount of drug dissolved was 90.2% and 83.4% for LPHNPs-1 and LPHNPs-5 respectively. Drug dissolution kinetics exhibited fickian diffusion best described by Korse-meyer Peppas model. The results suggested that chitosan and glyceryl monostearate based matrix LPHNPs could be used as promising approach for dissolution enhancement of ICZ which could further increase its bioavailability.

Biomimetic cell membrane-coated poly(lactic-co-glycolic acid) nanoparticles for biomedical applications.

Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) are commonly used for drug delivery because of their favored biocompatibility and suitability for sustained and controlled drug release. To prolong NP circulation time, enable target-specific drug delivery and overcome physiological barriers, NPs camouflaged in cell membranes have been developed and evaluated to improve drug delivery. Here, we discuss recent advances in cell membrane-coated PLGA NPs, their preparation methods, and their application to cancer therapy, management of inflammation, treatment of cardiovascular disease and control of infection. We address the current challenges and highlight future research directions needed for effective use of cell membrane-camouflaged NPs.

Solid lipid-based nanoparticulate system for sustained release and enhanced in-vitro cytotoxic effect of 5-fluorouracil on skin Melanoma and squamous cell carcinoma.

The present study aimed to prepare solid lipid-based nanoparticles (SLNs) using Precirol® ATO 5 as solid lipid and Poloxamer 188 and Tween 80 as surfactant and co-surfactant respectively, and SLNs-derived gel for sustained delivery, enhanced in-vitro cytotoxicity, enhanced cellular uptake of 5-FU and enhanced permeation of 5-FU across the skin. The 5-FU-loaded SLNs were prepared by the hot melt encapsulation method and converted into SLN-derived gel using a gelling agent (Carbopol 940). The 5-FU-loaded SLNs had a particle size in the range of 76.82±1.48 to 327±4.46 nm, zeta potential between -11.3±2.11 and -28.4±2.40 mV, and entrapment efficiency (%) in range of 63.46±1.13 and 76.08±2.42. The FTIR analysis depicted that there was no chemical interaction between 5-FU and formulation components. Differential scanning calorimetric analysis showed thermal stability of 5-FU in the nanoparticles and powdered X-ray diffraction analysis revealed successful incorporation of 5-FU in nanoparticles. The in-vitro release study of 5-FU-loaded SLNs showed biphasic release behavior with initial burst release followed by sustained release over 48 hr. The 5-FU-loaded SLNs showed a greater cytotoxic effect on skin melanoma (B16F10 cells) and squamous cell carcinoma (A-431 cells) as compared to free 5-FU drug solution after 48 hr. Flow cytometry and fluorescence microscopy displayed enhanced quantitative and qualitative cellular uptake of SLNs. The SLNs formulation showed acceptable safety and biocompatible profile after an acute toxicity study in Wistar rats. Moreover, ex-vivo permeation studies depicted 2.13±0.076 folds enhanced flux of 5-FU-loaded SLN derived gel compared to 5-FU plain gel, and skin retention studies revealed target efficiency (%) 2.54±0.03 of 5-FU-loaded SLN derived gel compared to 5-FU plain gel.

Polymeric Nanogel for Oral Delivery of the Chemotherapeutic Agent: Fabrication and Evaluation Alongside Toxicological Studies and Histopathological Examination.

Nanogel has attracted considerable attention as one of the most versatile drug delivery systems, especially for site-specific and/or time-controlled delivery of the chemotherapeutic agent. The main objective of this study was to prepare the polymeric nanogel characterized by Fourier transform infrared spectroscopy, x-ray diffraction, thermogravimetric analysis, differential scanning, and oral acute toxicity. Free radical polymerization was done for the fabrication of polymeric nanogel. Fourier transform infrared spectroscopy was used to confirm the successful free radical polymerization. Various techniques such as x-ray diffraction, differential scanning calorimetric, and thermogravimetric analysis measurement were used to investigate the thermal behavior and crystallinity of developed nanogel. Parameters such as swelling, drug loading, and in vitro drug release is enhanced as polymers and monomers concentrations increase while these parameters decrease in case of increasing crosslinker concentration. The oral biocompatibility results of developed nanogel exhibited no toxicity in rabbits. Histopathological changes were observed between empty and loaded group. The nanosized gel offers a specific surface area which increases the stability of loaded drug (oxaliplatin) and bioavailability of the drug (oxaliplatin) as compared to the conventional drug delivery systems.

Compritol-Based Alprazolam Solid Lipid Nanoparticles for Sustained Release of Alprazolam: Preparation by Hot Melt Encapsulation.

The current study was designed to investigate the feasibility of incorporating the water-insoluble lipophilic drug Alprazolam (Alp) into solid lipid nanoparticles (SLNs) to offer the combined benefits of the quick onset of action along with the sustained release of the drug. Therefore, compritol-based alprazolam-loaded SLNs (Alp-SLNs) would provide early relief from anxiety and sleep disturbances and long-lasting control of symptoms in patients with depression, thereby enhancing patient compliance. The optimized Alp-SLNs analyzed by DLS and SEM showed consistent particle size of 92.9 nm with PI values and standard deviation of the measurements calculated at <0.3 and negative surface charge. These characteristic values demonstrate the desired level of homogeneity and good physical stability of Alp-SLNs. The SLNs had a good entrapment efficiency (89.4%) and high drug-loading capacity (77.9%). SEM analysis revealed the smooth spherical morphology of the SLNs. The physical condition of alprazolam and absence of interaction among formulation components in Alp-SLNs was confirmed by FTIR and DSC analyses. XRD analysis demonstrated the molecular dispersion of crystalline alprazolam in Alp-SLNs. The in vitro release study implied that the release of Alp from the optimized Alp-SLN formulation was sustained as compared to the Alp drug solution because Alp-SLNs exhibited sustained release of alprazolam over 24 h. Alp-SLNs are a promising candidate to achieve sustained release of the short-acting drug Alp, thereby reducing its dosing frequency and enhancing patient compliance.

Development and In Vitro/Ex Vivo Evaluation of Lecithin-Based Deformable Transfersomes and Transfersome-Based Gels for Combined Dermal Delivery of Meloxicam and Dexamethasone.

Transfersomes (TFS) are the promising carriers for transdermal delivery of various low and high molecular weight drugs, owing to their self-regulating and self-optimizing nature. Herein, we report synthesis and characterization of TFS loaded with meloxicam (MLX), an NSAID, and dexamethasone (DEX), a steroid, for simultaneous transdermal delivery. The different formulations of TFS containing varying amounts of lecithin, Span 80, and Tween 80 (TFS-1 to TFS-6) were successfully prepared by thin-film hydration method. The size of ranged between 248 and 273 nm, zeta potential values covering from -62.6 to -69.5 mV, polydispersity index (PDI) values in between 0.329 and 0.526, and entrapment efficiency of MLX and DEX ranged between 63-96% and 48-81%, respectively. Release experiments at pH 7.4 demonstrated higher cumulative drug release attained with Tween 80 compared to Span 80-based TFS. The scanning electron microscopy (SEM) of selected formulations -1 and TFS-3 revealed spherical shape of vesicles. Furthermore, three optimized transfersomal formulations (based on entrapment efficiency, TFS-1, TFS-3, and TFS-5) were incorporated into carbopol-940 gels coded as TF-G1, TF-G3, and TF-G5. These transfersomal gels were subjected to pH, spreadability, viscosity, homogeneity, skin irritation, in vitro drug release, and ex vivo skin permeation studies, and the results were compared with plain (nontransfersomal) gel having MLX and DEX. TFS released 71.72% to 81.87% MLX in 12 h; whereas, DEX release was quantified as 74.72% to 83.72% in same time. Nevertheless, TF-based gels showed slower drug release; 51.54% to 59.60% for MLX and 48.98% to 61.23% for DEX. The TF-G systems showed 85.87% permeation of MLX (TF-G1), 68.15% (TF-G3), and 68.94% (TF-G5); whereas, 78.59%, 70.54%, and 75.97% of DEX was permeated by TF-G1, TF-G3, and TF-G5, respectively. Kinetic modeling of release and permeation data indicated to follow Korsmeyer-Peppas model showing diffusion diffusion-based drug moment. Conversely, plain gel influx was found mere 26.18% and 22.94% for MLX and DEX, respectively. These results suggest that TF-G loaded with MLX and DEX can be proposed as an alternate drug carriers for improved transdermal flux that will certainly increase therapeutic outcomes.

Unveiling and addressing implementation barriers of vaccination communication strategy: Perspectives from government officials at national and provincial levels.

Communication strategy is one of the support of primary health care (PHC) that can address demand-side barriers and socio-cultural factors to promote better services. Conversely, communication strategies have not been a distinct emphasis of vaccination research in the country until now. Therefore, this study aimed to find the elements that influence the provision of vaccination communication in Pakistan. Twenty-two semi-structured interviews with key stakeholders in vaccine communication were conducted using qualitative methodologies (Jan 2022-March 2022). The interviews revolved around factors affecting the implementation of communication. Interviews were transcribed and analyzed using thematic analysis. By using the SURE framework, numerous factors that affect vaccination communication were identified under three major themes such as organizational-level, constitutional, and community-level factors. Five subthemes marked the organizational-level factors such as constrained budget, infrastructure deficits, inconsistent comprehensive strategy, health workforce, and inadequate training. Two subthemes are derived regarding constitutional and community-level factors, respectively, such as governance and leadership, health communication interventions not a policymaker's priority, community perceptions and practices, and formal partnership lacking between national and local stakeholders. Additionally, employment of established communication committees, improved money allocation, engagement of traditional and religious institutions, and political backing were identified as solutions for improvement. Communication activities are an important part of immunization programs in order to increase vaccination coverage. To be able to execute communication interventions more successfully, national and provincial stakeholders must work together to identify the elements that affect vaccine provision. Additional rigorous implementation studies could aid in the development of clearer knowledge of the system-wide constraints obstructing the program's efficiency.

Natural Polymer-Based Graphene Oxide Bio-nanocomposite Hydrogel Beads: Superstructures with Advanced Potentials for Drug Delivery.

The current study sought to create graphene oxide-based superstructures for gastrointestinal drug delivery. Graphene oxide has a large surface area that can be used to load anti-cancer drugs via non-covalent methods such as surface adsorption and hydrogen bonding. To enhance the bio-applicability of graphene oxide, nano-hybrids were synthesized by encapsulating the graphene oxide into calcium alginate hydrogel beads through the dripping-extrusion technique. These newly developed bio-nanocomposite hybrid hydrogel beads were evaluated in structural analysis, swelling study, drug release parameters, haemolytic assay, and antibacterial activity. Doxorubicin served as a model drug. The drug entrapment efficiency was determined by UV-spectroscopy analysis and was found to be high at ⁓89% in graphene oxide hybrid hydrogel beads. These fabricated hydrogel beads ensure the drug release from a hybrid polymeric matrix in a more controlled and sustained pattern avoiding the problems associated with a non-hybrid polymeric system. The drug release study of 12 h shows about 83% release at pH 6.8. In vitro drug release kinetics proved that drug release was a Fickian mechanism. The cytotoxic effect of graphene oxide hybrid alginate beads was also determined by evaluating the morphology of bacterial cells and red blood cells after incubation. Additionally, it was determined that the sequential encapsulation of graphene oxide in alginate hydrogel beads hides its uneven edges and lessens the graphene oxide's negative impacts. Also, the antibacterial study and biocompatibility of fabricated hydrogel beads made them potential candidates for gastrointestinal delivery.

Lagenaria siceraria fruit: A review of its phytochemistry, pharmacology, and promising traditional uses.

Since ancient times, the Cucurbitaceae family is used as a therapeutic option in human medicine. This family has around 130 genera and 800 species. Researchers have studied the various plants of this family including Lagenaria siceraria due to their medicinal potential. Various properties are beneficial for human health, that have been attributed to L. siceraria like antioxidant, hypolipidemic, diuretic, laxative, hepatoprotective, analgesic, antihypertensive, cardioprotective, central nervous system stimulant, anthelmintic, free radical scavenging, immunosuppressive, and adaptogenic. The fruit of this plant is commonly used as a vegetable that has a low-calorie value. The species possess a diverse set of biological compounds like flavonoids, sterols, saponins, and terpenoids. Vitamins, choline, flavonoids, minerals, proteins, terpenoids, and other phytochemicals are also found in the edible parts of this plant. Besides 17 different amino acids, many minerals are reported to be present in the seeds of L. siceraria. According to the USDA nutritional database per 100 g of L. siceraria contains 14 Kcal energy, 3.39 g carbohydrates, 0.62 g protein, 0.2 g fat, and 0.5 g fiber. L. siceraria performs a wide range of pharmacological and physiological actions. The literature reviewed from various sources including PubMed, Science Direct, Google scholar, etc. shows the remarkable potential to treat various human and animal illnesses due to its' potent bioactive chemicals. The key objective of this thorough analysis is to present a summary of the data about the beneficial and harmful effects of L. siceraria intake on human health, as well as in veterinary fields.

Folate decorated lipid chitosan hybrid nanoparticles of 5-fluorouracil for enhanced anticancer efficacy against colon cancer.

The study aimed to develop folate decorated lipid chitosan hybrid nanoparticles for targeted delivery of 5-fluorouracil in colon cancer by utilizing the overexpressed folate receptors on the surface of HT-29 and HCT 116 cancer cell lines. The developed formulations were prepared by the ionic gelation method with slight modifications. The developed formulations exhibited spherical morphology, smaller particle size (158 to 225 nm), zeta potential (32.24 to 35.95 mV), PDI (0.19 to 0.35), and high encapsulation efficiency (85.3 % to 94.2 %) with optimal physicochemical characteristics. The in vitro release showed a biphasic release pattern with an initial burst release followed by a sustained release for 48 h. Moreover, the in vitro cell line study revealed that FA-CLPN-2 exhibited an enhanced cellular uptake and greater cytotoxic effect in HT-29 and HCT 116 cell lines compared to non-targeted CLPN-2 and free drug solution due to the folate receptor facilitated endocytosis process. The in vivo toxicity study revealed the safety and biocompatibility of the developed formulations in biological systems. The stability study demonstrates the stability of the developed formulations. Overall, these results suggest that the folate decorated lipid chitosan hybrid nanoparticles could be used as a potential delivery system for tumor-targeted therapy with reduced side effects.

Self-Nanoemulsification of Healthy Oils to Enhance the Solubility of Lipophilic Drugs.

The low aqueous solubility of many drugs reduces their bioavailability in the blood. Oils have been used for centuries to enhance the solubility of drugs; however, they can disturb the lipid profile of the patients. In this study, self-nanoemulsifying drug delivery systems of omega-3 fatty acids-rich oils are prepared and optimized for the delivery of lipophilic drugs. Rosuvastatin, a potent hypolipidemic drug, was used as a model lipophilic drug. Fish oil showed more than 7-fold higher solubility of rosuvastatin than other oils and therefore it was selected for the development of self-nanoemulsifying drug delivery systems (SNEDDS). Different combinations of surfactants and co-surfactants were screened and a surfactant mixture of Tween 80 (surfactant) and Capryol PGMC (cosurfactant) were selected for compatibility with fish oil and rosuvastatin. A pseudoternary phase diagram of oil, surfactant, and co-surfactant was designed to identify the emulsion region. The pseudoternary phase diagram predicted a 1:3 oil and surfactant mixture as the most stable ratio for the emulsion system. Then, a response-surface methodology (Box-Behnken design) was applied to calculate the optimal composition. After 17 runs, fish oil, Tween 80, and Capryol PGMC in proportions of 0.399, 0.67, and 0.17, respectively, were selected as the optimized formulation. The self-nanoemulsifying drug delivery systems showed excellent emulsification potential, robustness, stability, and drug release characteristics. In the drug release studies, SNEDDS released 100% of the payload in around 6 h whereas, release of the plain drug was less than 70% even after 12 h. Therefore, omega-3 fatty acids-rich healthy lipids have enormous potential to enhance the solubility of lipophilic drugs whereas, self-emulsification can be used as a simple and feasible approach to exploit this potential.

Core-shell Pluronic F127/chitosan based nanoparticles for effective delivery of methotrexate in the management of rheumatoid arthritis.

This study was designed to improve oral bioavailability of the methotrexate (MTX) by sustaining its release profile and integration into core-shell polymeric nanoparticles. The self-micellization and ionotropic gelation technique was employed which resulted into spherical shaped nanoparticles (181-417 nm) with encapsulation efficiency of 80.14% to 85.54%. Furthermore, Fourier Transform Infrared Spectroscopy and Differential Scanning Calorimetry analyses were carried out to investigate physicochemical and thermal stability of the produced engineered core shell nanoparticles of the methotrexate. . Entrapment of drug in polymeric core was confirmed by X-ray diffraction analysis. In-vitro sustained release behavior of nanoparticles was observed at pH 6.8 for 48 h while low drug release was observed at pH 1.2 due to pH-responsive nature of Pluronic F127. Acute toxicity study confirmed safety and biocompatible profile of nanoparticles. MTX loaded polymeric nanoparticles ameliorated the pharmacokinetic profile (8 folds greater half-life, 6.26 folds higher AUC0-t and 3.48 folds higher mean residence time). In vivo study conducted in rat model depicted the improved therapeutic efficacy and healing of arthritis through MTX loaded polymeric nanoparticles, preferentially attributable to high accretion of MTX in the inflamed site. In conclusion, MTX loaded polymeric nanoparticles is an attractive drug delivery strategy for an effective management and treatment of rheumatoid arthritis.

Investigation of Eutectic Mixtures of Fatty Acids as a Novel Construct for Temperature-Responsive Drug Delivery.

Background: Most of the traditional nanocarriers of cancer therapeutic moieties present dose-related toxicities due to the uptake of chemotherapeutic agents in normal body cells. The severe life-threatening effects of systemic chemotherapy are well documented. Doxorubicin, DOX is the most effective antineoplastic agent but with the least specific action that is responsible for severe cardiotoxicity and myelosuppression that necessitates careful monitoring while administering. Stimuli-sensitive/intelligent drug delivery systems, specifically those utilizing temperature as an external stimulus to activate the release of encapsulated drugs, have become a subject of recent research. Thus, it would be ideal to have a nanocarrier comprising safe excipients and controllable drug release capacity to deliver the drug at a particular site to minimize unwanted and toxic effects of chemotherapeutics. We have developed a simple temperature-responsive nanocarrier based on eutectic mixture of fatty acids. This study aimed to develop, physicochemically characterize and investigate the biological safety of eutectic mixture of fatty acids as a novel construct for temperature-responsive drug release potential. Methods: We have developed phase change material, PCM, based on a series of eutectic mixtures of fatty acids due to their unique and attractive physicochemical characteristics such as safety, stability, cost-effectiveness, and ease of availability. The reversible solid-liquid phase transition of PCM is responsible to hold firm or actively release the encapsulated drug. The eutectic mixtures of fatty acids (stearic acid and myristic acid) along with liquid lipid (oleic acid) were prepared to exhibit a tunable thermoresponsive platform. Doxorubicin-loaded lipid nanocarriers were successfully developed with combined hot melt encapsulation (HME) and sonication method and characterized to achieve enhanced permeability and retention (EPR) effect-based solid tumor targeting in response to exogenous temperature stimulus. The cytotoxicity against melanoma cell lines and in vivo safety studies in albino rats was also carried out. Results: Doxorubicin-loaded lipid nanocarriers have a narrow size distribution (94.59-219.3 nm), and a PDI (0.160-0.479) as demonstrated by photon correlation microscopy and excellent colloidal stability (Z.P value: -22.7 to -32.0) was developed. Transmission electron microscopy revealed their spherical morphology and characteristics of a monodispersed system. A biphasic drug release pattern with a triggered drug release at 41°C and 43°C and a sustained drug release was observed at 37°C. The thermoresponsive cytotoxic potential was demonstrated in B16F10 cancer cell lines. Hemolysis assay and acute toxicity studies with drug-free and doxorubicin lipid nanocarrier formulations provided evidence for their non-toxic nature. Conclusion: We have successfully developed a temperature-responsive tunable platform with excellent biocompatibility and intelligent drug release potential. The formulation components being from natural sources present superior characteristics in terms of cost, compatibility with normal body cells, and adaptability to preparation methods. The reported preparation method is adapted to avoid complex chemical processes and the use of organic solvents. The lipid nanocarriers with tunable thermoresponsive characteristics are promising biocompatible drug delivery systems for improved localized delivery of chemotherapeutic agents.

Natural polysaccharide-based biodegradable polymeric platforms for transdermal drug delivery system: a critical analysis.

Natural biodegradable polymers generally include polysaccharides (starch, alginate, chitin/chitosan, hyaluronic acid derivatives, etc.) and proteins (collagen, gelatin, fibrin, etc.). In transdermal drug delivery systems (TDDS), these polymers play a vital role in controlling the device's drug release. It is possible that natural polymers can be used for TDDS to attain predetermined drug delivery rates due to their physicochemical properties. These polymers can be employed to market products and scale production because they are readily available and inexpensive. As a result of these polymers, new pharmaceutical delivery systems can be developed that is both regulated and targeted. The focus of this article is the application of a biodegradable polymeric platform based on natural polymers for TDDS. Due to their biocompatibility and biodegradability, natural biodegradable polymers are frequently used in biomedical applications. Additionally, these natural biodegradable polymers are being studied for their characteristics and behaviors.