Functionalized and Nonfunctionalized Nanosystems for Mitochondrial Drug Delivery with Metallic Nanoparticles.

Background: The application of metallic nanoparticles as a novel therapeutic tool has significant potential to facilitate the treatment and diagnosis of mitochondria-based disorders. Recently, subcellular mitochondria have been trialed to cure pathologies that depend on their dysfunction. Nanoparticles made from metals and their oxides (including gold, iron, silver, platinum, zinc oxide, and titanium dioxide) have unique modi operandi that can competently rectify mitochondrial disorders. Materials: This review presents insight into the recent research reports on exposure to a myriad of metallic nanoparticles that can alter the dynamic ultrastructure of mitochondria (via altering metabolic homeostasis), as well as pause ATP production, and trigger oxidative stress. The facts and figures have been compiled from more than a hundred PubMed, Web of Science, and Scopus indexed articles that describe the essential functions of mitochondria for the management of human diseases. Result: Nanoengineered metals and their oxide nanoparticles are targeted at the mitochondrial architecture that partakes in the management of a myriad of health issues, including different cancers. These nanosystems not only act as antioxidants but are also fabricated for the delivery of chemotherapeutic agents. However, the biocompatibility, safety, and efficacy of using metal nanoparticles is contested among researchers, which will be discussed further in this review.

Printing Methods in the Production of Orodispersible Films.

Orodispersible film (ODF) formulations are promising and progressive drug delivery systems that are widely accepted by subjects across all the age groups. They are traditionally fabricated using the most popular yet conventional method called solvent casting method. The most modern and evolving method is based on printing technologies and such printed products are generally termed as printed orodispersible films (POFs). This modern technology is well suited to fabricate ODFs across different settings (laboratory or industrial) in general and in a pharmacy setting in particular. The present review provides an overview of various printing methods employed in fabricating POFs. Particularly, it provides insight about preparing POFs using inkjet, flexographic, and three-dimensional printing (3DP) or additive manufacturing techniques like filament deposition modeling, hot-melt ram extrusion 3DP, and semisolid extrusion 3DP methods. Additionally, the review is focused on patenting trends in POFs using ESPACENET, a European Patent Office search database. Finally, the review captures future market potential of 3DP in general and ODFs market potential in particular.

Gastroretentive bilayer film for sustained release of atorvastatin calcium and immediate release of amlodipine besylate: pharmaceutical, pharmacokinetic evaluation, and IVIVC.

The present study was aimed to optimize capsulated unfolding type gastroretentive bilayer film constituting immediate release (IR) layer of amlodipine besylate and sustained release (SR) layer of atorvastatin calcium. A three-factor, three-level Box-Behnken-design was used to optimize bilayer film with dual-release characteristics. The selected independent variables were HPMC-K3, Eudragit RSPO, and Carbopol 934P and the responses were floating duration, swelling index, and in vitro release from SR layer in 8 h. The films were also assessed for pharmacotechnical characteristics, release kinetics, DSC, FTIR, and SEM. The pharmacokinetics of the drugs from the optimized formulation was compared with the marketed formulation in rabbits. The capsulated accordion film unfolded and provided SR of atorvastatin for 8 h (96.76% ± 0.71) and IR of amlodipine within 25 min (98.07% ± 0.62) for the optimized formulation (F14). The swelling index and floating duration for the optimized formulation were 140.48 ± 0.57 and 8.53 ± 0.10 h, respectively. Results of pharmacokinetics showed that faster absorption of amlodipine and improved bioavailability (2.16-fold) of atorvastatin in blood was made available through bilayer film. In vitro-in vivo correlation was established using numerical deconvolution method. It can be concluded that the capsulated gastroretentive system provided site specific simultaneous SR of antihyperlidemic drug and IR of antihypertensive drug as single pill that has therapeutic potential to manage cardiovascular risk.

Investigating the penetrating potential of nanocomposite ß-cycloethosomes: development using central composite design, in vitro and ex vivo characterization.

CONTEXT: Atopic dermatitis (AD) is a chronic skin disease characterized by inflammation of the skin and has exhibited remarkable repercussions on human life across the globe. Fluocinolone acetonide (FA), a topical corticosteroid is employed in the treatment of atopic dermatitis, but suffers from limited penetration into deeper epidermis of atopic skin. OBJECTIVE: The present investigation was focused to explore the utility of ß-cylcoethosomes in improvising the penetration deep into the skin. MATERIALS AND METHODS: ß-Cylcoethosomes developed using ß-cycloamylose by injection method were evaluated for vesicle size, entrapment efficiency and in vitro release. Central Composite design employed for the preparation depicted FA8 as an optimized formulation which was then formulated as dermatological gel using carbomer 934P as a gel base. The gels were characterized for pH, viscosity, drug content and in vitro permeability. RESULTS AND DISCUSSION: Optimized formulation (FA8) showed maximum desirability (0.795) with vesicle size of 228.33 ± 1.23 nm), EE (82.49 ± 1.21%) and CDR (90.90 ± 0.29%). FA8-loaded gels showed maximum in vitro permeability as found in BG and BGP (83.22 ± 0.72% and 84.02 ± 0.87). BG was selected as an optimized gel and compared with optimized reference ethosomal gel and control gel. CLSM studies depicted deeper uniform penetration of fluorescent dye deep into the epidermis via BG. Improved penetration was observed due to the synergistic effect exerted by ethanol and ß-cycloamylose. CONCLUSION: ß-cylcoethosomes proved to be a promising carrier for improvised penetration of fluocinolone acetonide via topical gel.

Pilosebaceous targeting by isotretenoin-loaded invasomal gel for the treatment of eosinophilic pustular folliculitis: optimization, efficacy and cellular analysis.

CONTEXT: Eosinophilic pustular folliculitis is a secondary symptom associated with HIV infection appears as levels of CD4 lymphocyte cells and T4 lymphocyte cell. Isotretinoin, an analog of vitamin A (retinoid) alters the DNA transcription mechanism and interferes in the process of DNA formation. It also inhibits the eosinophilic chemotactic factors present in sebaceous lipids and in the stratum corneum of patients suffering from this ailment. OBJECTIVE: The present research was aimed to formulate isotretenoin-loaded invasomal gel to deliver and target the drug to pilosebaceous follicular unit. METHODS: Nine invasomal formulations (F1-F9) were prepared applying 32 factorial designs and characterized. RESULTS: Formulation F9 was selected as optimized formulation due to optimum results and highest %CDP of 85.94 ± 1.86% in 8 h. Transmission electron microscopy (TEM) suggested uniformity in vesicles shape and size in F9 and developed as invasomal gel (IG). LIMITATIONS: Clinical phase-I, phase-II, and phase-III studies will be required before using on human patients. CONCLUSION: Confocal laser scanning microscopy (CLSM) validates that IG successfully reaches the pilosebaceous follicular unit and further studied on cell line (SZ-95) exhibited IC50 of ≤8 (25 µM of isotretenoin). Cell cycle analysis confirmed IG arrested the cell growth up to 82% with insignificant difference to pure isotretenion.

Preparation and evaluation of a buflomedil hydrochloride niosomal patch for transdermal delivery.

CONTEXT: Niosomes are the non-ionic surfactant vesicles obtained on hydration of synthetic non-ionic surfactants. These are the promising vehicles for effective transdermal drug delivery. OBJECTIVE: The present research work was aimed to develop niosomal-based transdermal buflomedil hydrochloride patch containing a stable formulation with improved drug permeation. MATERIALS AND METHODS: Niosomes were prepared by solvent evaporation method using 32 factorial design. All the formulations were evaluated for vesicle size, zeta potential and percent entrapment efficiency. Optimized niosomal and liposomal formulation were loaded into a patch system. All the patches were then characterized for drug-excipient interaction study, scanning electron microscopy, pharmacotechnical properties and in vitro permeation studies. RESULT: F9 formulation having optimum vesicle size (10.09 ± 1.2 µm), highest zeta potential (-85.4 ± 0.56 mV) and maximum percent entrapment efficiency (97.09 ± 0.11%) was selected as optimized formulation. In case of liposomes, formulation F12 was selected. Patches loaded with niosomes showed 95.12 ± 1.19% cumulative amount of drug permeated as compared to liposomal vesicle-loaded patches which showed 82.21 ± 1.24% and control patches 70.10 ± 1.33%. DISCUSSION: Flux, permeation rate and permeability coefficient were found to be higher in case of niosomal patches as compared to liposomal patches and control patches. Surfactant present in niosomes act as a penetration enhancer which contribute in the permeation enhancement of buflomedil hydrochloride from niosomes. CONCLUSION: Thus, it was concluded that niosomal vesicles represented to be an efficient and stable vesicular carrier for transdermal delivery of buflomedil hydrochloride.

Optimization studies on development and evaluation of papain-based in situ gelling system for chemomechanical caries removal.

CONTEXT: Chemomechanical caries removal is a non-invasive technique that eliminates infected dentine via a chemical agent. Papain, owing to its proteolytic nature causes disruption of degraded collagen fibrils that helps easy removal of the caries and has both bacteriostatic and bactericidal action. OBJECTIVE: The objective of the present work was to formulate and evaluate papain-based in situ gelling system for chemomechanical caries removal, based on the concept of pH-triggered in situ gelation and evaluate its pharmaceutical and chemomechanical characteristics. MATERIAL AND METHODOLOGY: A 32 full factorial design was employed to formulate the in situ gels. Carbopol 934 and HPMC K15M were designated as two independent variables, each utilized at three different levels and the dependent variables were gelling capacity, viscosity and % cumulative drug permeated (CDP). The optimized formulation was assessed for ex vivo clinical efficacy by SEM, micro-tensile bond strength and antibacterial activity. RESULTS: Formulation F3 with % CDP of 10.13 ± 0.43% and optimum gelling and viscosity characteristics was optimized. The efficacy of F3 was confirmed by enhanced micro-tensile bond strength of 38.48 ± 4.14 Mpa compared to 29.42 ± 2.33 Mpa of control group and SEM. CONCLUSION: An economically viable papain-based in situ gelling system with clinical potential for caries removal with enhanced bonding ability was successfully developed.

Colon specific CODES based Piroxicam tablet for colon targeting: statistical optimization, in vivo roentgenography and stability assessment.

This study was aimed to statistically optimize CODES™ based Piroxicam (PXM) tablet for colon targeting. A 3(2) full factorial design was used for preparation of core tablet that was subsequently coated to get CODES™ based tablet. The experimental design of core tablets comprised of two independent variables: amount of lactulose and PEG 6000, each at three different levels and the dependent variable was %CDR at 12 h. The core tablets were evaluated for pharmacopoeial and non-pharmacopoeial test and coated with optimized levels of Eudragit E100 followed by HPMC K15 and finally with Eudragit S100. The in vitro drug release study of F1-F9 was carried out by change over media method (0.1 N HCl buffer, pH 1.2, phosphate buffer, pH 7.4 and phosphate buffer, pH 6.8 with enzyme ß-galactosidase 120 IU) to select optimized formulation F9 that was subjected to in vivo roentgenography. Roentgenography study corroborated the in vitro performance, thus providing the proof of concept. The experimental design was validated by extra check point formulation and Diffuse Reflectance Spectroscopy revealed absence of any interaction between drug and formulation excipients. The shelf life of F9 was deduced as 12 months. Conclusively, colon targeted CODES™ technology based PXM tablets were successfully optimized and its potential of colon targeting was validated by roentgenography.

Development of acetazolamide-loaded, pH-triggered polymeric nanoparticulate in situ gel for sustained ocular delivery: in vitro. ex vivo evaluation and pharmacodynamic study.

The objective of research was to develop a novel pH-triggered polymeric nanoparticulate in situ gel (NP-ISG) for ophthalmic delivery of acetazolamide (ACZ) to enhance the conjunctival permeation and precorneal residence time of the formulation by overcoming the limitations of protective ocular barriers. Nanoparticles (NP1--NP12) were developed by nanoprecipitation method and evaluated for pharmacotechnical characteristics including transmission electron microscopy. The optimized formulation, NP10 was dispersed in carbopol 934 P to form nanoparticulate in situ gels (NP-ISG1--NP-ISG5). NP-ISG5 was selected as optimized formulation on the basis of gelation ability and residence time. Ex vivo transcorneal permeation study exhibited significantly higher ACZ permeation from NP-ISG5 (74.50 ± 2.20 mg/cm(2)) and NP10 (93.5 ± 2.25 mg/cm(2)) than eye drops (20.08 ± 3.12 mg/cm(2)) and ACZ suspension (16.03 ± 2.14). Modified Draize test with zero score indicated nonirritant property of NP-ISG5. Corneal toxicity study revealed no visual signs of tissue damage. Further, NP-ISG5 when tested for hypotensive effect on intraocular pressure (IOP) in rabbits revealed that NP-ISG5 caused significant decrease in IOP (p < 0.05) in comparison to eye drops. Conclusively, NP-ISG5 may offer intensive management of glaucoma via higher permeation, prolonged precorneal residence time and sustained drug release along with higher in vitro efficacy, safety and patient compliance.

Effect of melt sonocrystallization on pharmacotechnical properties of paracetamol, indomethacin and mefenamic acid characterized by dynamic laser scattering and its impact on solubility.

The purpose of the research was to employ a novel particle engineering technique-melt sonocrystallization (MSC) for some nonsteroidal anti-inflammatory drugs for development of more soluble forms of the drugs without the use of excipients. The original forms of Paracetamol (OFPCM), Indomethacin (OFIMC) and Mefenamic acid (OFMA) were subjected to MSC to improve physicochemical properties. MSC forms of PCM, IMC and MA were subjected to dynamic laser scattering for particle size analysis to quantize mean particle size, specific surface area, interquartile coefficient of skewness, kurtosis and span. Rheological and solubility analysis, X-ray powder diffraction and scanning electron microscopy were conducted for validating the effect of MSC on powder particles. On melt sonocrystallized form of drug powders exhibited improved micromeritic properties, the mean particle size was reduced while the specific surface area increased effectively. Frequency distribution curves showed reduction in asymmetry and skewness that was confirmed by interquartile coefficient of skewness values. Equilibrium solubility of MSC form of PCM, IMC and MA was higher than the original forms. Similarly the intrinsic dissolution rate was approximately 1.5 times higher in comparison to original form of drugs. X-ray powder diffraction shows decreased relative intensities of peaks of MSC forms due to reduction in the crystallinity that was confirmed by visualization of MSC particles by scanning electron microscopy. Conclusively, MSC is a promising cost-effective technique that may afford powder with improved flow and formulative properties as well as improved solubility and dissolution.

Formulation and in vitro evaluation of prolonged release floating microspheres of atenolol using multicompartment dissolution apparatus.

The aim of the present work was to prepare floating microspheres of atenolol as prolonged release multiparticulate system and evaluate it using novel multi-compartment dissolution apparatus. Atenolol loaded floating microspheres were prepared by emulsion solvent evaporation method using 3² full factorial design. Formulations F1 to F9 were prepared using two independent variables (polymer ratio and % polyvinyl alcohol) and evaluated for dependent variables (particle size, percentage drug entrapment efficiency and percentage buoyancy). The formulation(F8) with particle size of 329 ± 2.69 µm, percentage entrapment efficiency of 61.33% and percentage buoyancy of 96.33% for 12 h was the of optimized formulation (F8). The results of factorial design revealed that the independent variables significantly affected the particle size, percentage drug entrapment efficiency and percentage buoyancy of the microspheres. In vitro drug release study revealed zero order release from F8 (98.33% in 12 h). SEM revealed the hollow cavity and smooth surface of the hollow microspheres.

Design and development of a novel pH triggered nanoemulsified in-situ ophthalmic gel of fluconazole: ex-vivo transcorneal permeation, corneal toxicity and irritation testing.

The objective of the present research was to develop a novel pH triggered nanoemulsified in-situ gel (NE-ISG) for ophthalmic delivery of fluconazole (FLZ) to enhance the permeation and residence time of the formulation, by overcoming the limitations associated with protective ocular barriers. Pseudoternary phase diagrams were constructed using capmul MCM (oil phase), tween 80 (surfactant) and transcutol P (cosurfactant) to identify the NE region. Nanoemulsions (NE1-NE6) of FLZ were prepared by spontaneous emulsification method and evaluated for various pharmacotechnical characteristics. NE4 was selected as optimized NE and was dispersed in carbopol 934 solution to form nanoemulsified sols (NE-ISG1 to NE-ISG5) that were expected to convert in to in-situ gels at corneal pH (7.4). The optimized NE-ISG was selected on the basis of gelation ability with a residence time up to or more than 6 h. Ex-vivo transcorneal permeation study displayed significantly higher (p < 0.05) permeation of FLZ from NE-ISG5 (337.67 µg/cm(2)) and NE4 (419.30 µg/cm(2)) than the commercial eye drops (112.92 µg/cm(2)). Hen's egg test-Chorioallantoic membrane (HET-CAM) test with zero score indicated the non-irritant property of developed NE-ISG5. Corneal toxicity study revealed no visual signs of tissue damage. Hence it can be concluded that NE-ISG5 may offer a more intensive treatment of ocular fungal infections due to higher permeation, prolonged precorneal residence time and sustained drug release along with higher in-vitro efficacy, safety and greater patient compliance.

Development of thermodynamically stable nanostructured lipid carrier system using central composite design for zero order permeation of econazole nitrate through epidermis.

The investigation was aimed at developing thermodynamically stable topical delivery system of nanostructured lipid carrier of econazole nitrate (EN) for the treatment of deep seated fungal infection by improving its permeability. Fifteen formulations (F1-F15) of nanostructured lipid carriers (NLCs) were prepared by solvent injection technique using central composite design and characterized for particle size and % entrapment efficiency. Closeness in the results, guided the selection of five NLC formulations which were formulated as hydrogels (G1-G5) using Carbopol 934. The permeation studies of gels demonstrated G3 with flux rate of 3.21 ± 0.03 µg/cm(2)/min (> target flux of 1.46 µg/cm(2)/min) as the best formulation that exhibited zero order permeation. The amount of drug/unit area demonstrated linear dependency on flux rate. Confocal laser scanning microscopy demonstrated penetration of rhodamine red till the stratum basale due to hydration of stratum corneum. Hydrogel G3 containing NLC formulation (F5) was selected as the optimized topical gel. TEM of F5 revealed spherical particles that presented low recrystallization index of 72.35%. Stability profile for 90 days revealed insignificant change (p < 0.05) in the particle size and zeta potential indicating substantial stability of the system. Thus, EN-loaded NLC indicated better permeability and thermodynamic stability as effective topical delivery system for deep seated fungal infection.

Pharmaceutical evaluation and dynamic vapor sorption studies of fast dissolving intraoral films of Loratadine.

The aim of the study was to develop intraoral films (IOFs) of loratadine and to assess the storage conditions by dynamic vapour sorption studies. The excipient selection was guided by drug excipient compatibility studies and the incompatibility of loratadine with dibutylphathalate and Tween20 was confirmed by Electro-spray Ionization Mass Spectrometry. Thus intaroral films were developed using HPMC E-15 LV and polyvinyl alcohol (PVA) as lone and mixed film formers to get eighteen formulations (F1- F18) that varied in the type and amount of plasticizer used. Four formulations selected on the basis of pharmacotechnical characteristics were improvised by inclusion of Poloxamer407 that lowered the dissolving time to the tune of 36-55%. Dynamic vapour sorption studies of the improvised films (PF1-PF4) demonstrated an increase of 2% by weight at 50% relative humidity (RH) and 25°C suggesting storage of the films below the stated conditions. In vitro drug release studies in phosphate buffer pH 6.8 demonstrated more than 94% cumulative drug release from the formulations. Analysis of model independent parameters identified PF2 as the best formulation that was nine times superior in its dissolution efficiency to Lorafast tablets(®).

Inulin-based tablet in capsule device for variable multipulse delivery of aceclofenac: optimization and in vivo roentgenography.

The aim of the study was to develop single-unit tablet in capsule system of aceclofenac for the treatment of late night pain and morning stiffness associated with rheumatoid arthritis. The system was conceptualized as a three-component design (1) a hard gelatin enteric-coated capsule (for carrying two pulses), (2) first-pulse granules (for rapid release in intestine), and (2) second-pulse matrix tablet (for slow release in colon). An appropriate integration of pH-sensitive (Eudragit S100) and bacteria-responsive (inulin) functions, on the basis of 3(2) factorial design, led to formulation of TICS 1-9 that were screened for in vitro release. TICS 2 with biphasic drug release of 98.64% from first-pulse granules in simulated intestinal fluid (12 h) and 97.82% from second-pulse matrix tablet in simulated colonic fluid (24 h) was the optimized formulation that exhibited Fickian diffusion of drug (n=0.363). In vivo fluoroscopy in rats traced the intact tablet to colon in 7.5 h that got eroded at the tenth hour. This demonstrated the colon-specific delivery of the matrix tablet affirming the potential of the system to obviate the need for two-time administration of drug at odd hours. The experimental design was validated by extra design check point, and diffuse reflectance spectroscopy and DSC revealed absence of chemical interaction between the formulation excipients.

Thermally triggered mucoadhesive in situ gel of loratadine: ß-cyclodextrin complex for nasal delivery.

The aim of the present study was to increase the solubility of an anti-allergic drug loratadine by making its inclusion complex with ß-cyclodextrin and to develop it's thermally triggered mucoadhesive in situ nasal gel so as to overcome first-pass effect and consequently enhance its bioavailability. A total of eight formulations were prepared by cold method and optimized by 2(3) full factorial design. Independent variables (concentration of poloxamer 407, concentration of carbopol 934 P, and pure drug or its inclusion complex) were optimized in order to achieve desired gelling temperature with sufficient mucoadhesive strength and maximum permeation across experimental nasal membrane. The design was validated by extra design checkpoint formulation (F9) and Pareto charts were used to help eliminate terms that did not have a statistically significant effect. The response surface plots and possible interactions between independent variables were analyzed using Design Expert Software 8.0.2 (Stat Ease, Inc., USA). Faster drug permeation with zero-order kinetics and target flux was achieved with formulation containing drug: ß-cyclodextrin complex rather than those made with free drug. The optimized formulation (F8) with a gelling temperature of 28.6±0.47°C and highest mucoadhesive strength of 7,676.0±0.97 dyn/cm2 displayed 97.74±0.87% cumulative drug permeation at 6 h. It was stable for over 3 months and histological examination revealed no remarkable damage to the nasal tissue.

Comparative evaluation of porous versus nonporous mucoadhesive films as buccal delivery system of glibenclamide.

The present research work focused on the comparative assessment of porous versus nonporous films in order to develop a suitable buccoadhesive device for the delivery of glibenclamide. Both films were prepared by solvent casting technique using the 3(2) full factorial design, developing nine formulations (F1-F9). The films were evaluated for ex vivo mucoadhesive force, ex vivo mucoadhesion time, in vitro drug release (using a modified flow-through drug release apparatus), and ex vivo drug permeation. The mucoadhesive force, mucoadhesion time, swelling index, and tensile strength were observed to be directly proportional to the content of HPMC K4M. The optimized porous film (F4) showed an in vitro drug release of 84.47 ± 0.98%, ex vivo mucoadhesive force of 0.24 ± 0.04 N, and ex vivo mucoadhesion time of 539.11 ± 3.05 min, while the nonporous film (NF4) with the same polymer composition showed a release of 62.66 ± 0.87%, mucoadhesive force of 0.20 ± 0.05 N, and mucoadhesive time of 510 ± 2.00 min. The porous film showed significant differences for drug release and mucoadhesion time (p < 0.05) versus the nonporous film. The mechanism of drug release was observed to follow non-Fickian diffusion (0.1 < n < 0.5) for both porous and nonporous films. Ex vivo permeation studies through chicken buccal mucosa indicated improved drug permeation in porous films versus nonporous films. The present investigation established porous films to be a cost-effective buccoadhesive delivery system of glibenclamide.

Local Drug Delivery Strategies towards Wound Healing.

A particular biological process known as wound healing is connected to the overall phenomena of growth and tissue regeneration. Several cellular and matrix elements work together to restore the integrity of injured tissue. The goal of the present review paper focused on the physiology of wound healing, medications used to treat wound healing, and local drug delivery systems for possible skin wound therapy. The capacity of the skin to heal a wound is the result of a highly intricate process that involves several different processes, such as vascular response, blood coagulation, fibrin network creation, re-epithelialisation, collagen maturation, and connective tissue remodelling. Wound healing may be controlled with topical antiseptics, topical antibiotics, herbal remedies, and cellular initiators. In order to effectively eradicate infections and shorten the healing process, contemporary antimicrobial treatments that include antibiotics or antiseptics must be investigated. A variety of delivery systems were described, including innovative delivery systems, hydrogels, microspheres, gold and silver nanoparticles, vesicles, emulsifying systems, nanofibres, artificial dressings, three-dimensional printed skin replacements, dendrimers and carbon nanotubes. It may be inferred that enhanced local delivery methods might be used to provide wound healing agents for faster healing of skin wounds.

Codelivery of Phytochemicals with Conventional Anticancer Drugs in Form of Nanocarriers.

Anticancer drugs in monotherapy are ineffective to treat various kinds of cancer due to the heterogeneous nature of cancer. Moreover, available anticancer drugs possessed various hurdles, such as drug resistance, insensitivity of cancer cells to drugs, adverse effects and patient inconveniences. Hence, plant-based phytochemicals could be a better substitute for conventional chemotherapy for treatment of cancer due to various properties: lesser adverse effects, action via multiple pathways, economical, etc. Various preclinical studies have demonstrated that a combination of phytochemicals with conventional anticancer drugs is more efficacious than phytochemicals individually to treat cancer because plant-derived compounds have lower anticancer efficacy than conventional anticancer drugs. Moreover, phytochemicals suffer from poor aqueous solubility and reduced bioavailability, which must be resolved for efficacious treatment of cancer. Therefore, nanotechnology-based novel carriers are employed for codelivery of phytochemicals and conventional anticancer drugs for better treatment of cancer. These novel carriers include nanoemulsion, nanosuspension, nanostructured lipid carriers, solid lipid nanoparticles, polymeric nanoparticles, polymeric micelles, dendrimers, metallic nanoparticles, carbon nanotubes that provide various benefits of improved solubility, reduced adverse effects, higher efficacy, reduced dose, improved dosing frequency, reduced drug resistance, improved bioavailability and higher patient compliance. This review summarizes various phytochemicals employed in treatment of cancer, combination therapy of phytochemicals with anticancer drugs and various nanotechnology-based carriers to deliver the combination therapy in treatment of cancer.

Amelioration of Cancer Employing Chitosan, Its Derivatives, and Chitosan-Based Nanoparticles: Recent Updates.

The limitations associated with the conventional treatment of cancer have necessitated the design and development of novel drug delivery systems based mainly on nanotechnology. These novel drug delivery systems include various kinds of nanoparticles, such as polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, hydrogels, and polymeric micelles. Among the various kinds of novel drug delivery systems, chitosan-based nanoparticles have attracted the attention of researchers to treat cancer. Chitosan is a polycationic polymer generated from chitin with various characteristics such as biocompatibility, biodegradability, non-toxicity, and mucoadhesiveness, making it an ideal polymer to fabricate drug delivery systems. However, chitosan is poorly soluble in water and soluble in acidic aqueous solutions. Furthermore, owing to the presence of reactive amino groups, chitosan can be chemically modified to improve its physiochemical properties. Chitosan and its modified derivatives can be employed to fabricate nanoparticles, which are used most frequently in the pharmaceutical sector due to their possession of various characteristics such as nanosize, appropriate pharmacokinetic and pharmacodynamic properties, non-immunogenicity, improved stability, and improved drug loading capacity. Furthermore, it is capable of delivering nucleic acids, chemotherapeutic medicines, and bioactives using modified chitosan. Chitosan and its modified derivative-based nanoparticles can be targeted to specific cancer sites via active and passive mechanisms. Based on chitosan drug delivery systems, many anticancer drugs now have better effectiveness, potency, cytotoxicity, or biocompatibility. The characteristics of chitosan and its chemically tailored derivatives, as well as their use in cancer therapy, will be examined in this review.