A Novel PEtOx-Based Nanogel Targeting Prostate Cancer Cells for Drug Delivery.

This study focuses on creating a specialized nanogel for targeted drug delivery in cancer treatment, specifically targeting prostate cancer. This nanogel (referred to as SGK 636/Peptide 563/PEtOx nanogel) is created using hydrophilic poly(2-ethyl-2-oxazoline) (PEtOx) through a combination of living/cationic ring-opening polymerization (CROP) and alkyne-azide cycloaddition (CuAAC) "click" chemical reactions. A fluorescent probe (BODIPY) is also conjugated with the nanogel to monitor drug delivery. The characterizations through 1 H-NMR, and FT-IR, SEM, TEM, and DLS confirm the successful production of uniform, and spherical nanogels with controllable sizes (100 to 296 nm) and stability in physiological conditions. The biocompatibility of nanogels is evaluated using MTT cytotoxicity assays, revealing dose-dependent cytotoxicity. Drug-loaded nanogels exhibited significantly higher cytotoxicity against cancer cells in vitro compared to drug-free nanogels. Targeting efficiency is examined using both peptide-conjugated and peptide-free nanogels, with the intracellular uptake of peptide 563-conjugated nanogels by tumor cells being 60-fold higher than that of nanogels without the peptide. The findings suggest that the prepared nanogel holds great potential for various drug delivery applications due to its ease of synthesis, tunable functionality, non-toxicity, and enhanced intracellular uptake in the tumor region.

Polymeric-Micelle-Based Delivery Systems for Nucleic Acids.

Nucleic acids can modulate gene expression specifically. They are increasingly being utilized and show huge potential for the prevention or treatment of various diseases. However, the clinical translation of nucleic acids faces many challenges due to their rapid clearance after administration, low stability in physiological fluids and limited cellular uptake, which is associated with an inability to reach the intracellular target site and poor efficacy. For many years, tremendous efforts have been made to design appropriate delivery systems that enable the safe and effective delivery of nucleic acids at the target site to achieve high therapeutic outcomes. Among the different delivery platforms investigated, polymeric micelles have emerged as suitable delivery vehicles due to the versatility of their structures and the possibility to tailor their composition for overcoming extracellular and intracellular barriers, thus enhancing therapeutic efficacy. Many strategies, such as the addition of stimuli-sensitive groups or specific ligands, can be used to facilitate the delivery of various nucleic acids and improve targeting and accumulation at the site of action while protecting nucleic acids from degradation and promoting their cellular uptake. Furthermore, polymeric micelles can be used to deliver both chemotherapeutic drugs and nucleic acid therapeutics simultaneously to achieve synergistic combination treatment. This review focuses on the design approaches and current developments in polymeric micelles for the delivery of nucleic acids. The different preparation methods and characteristic features of polymeric micelles are covered. The current state of the art of polymeric micelles as carriers for nucleic acids is discussed while highlighting the delivery challenges of nucleic acids and how to overcome them and how to improve the safety and efficacy of nucleic acids after local or systemic administration.

Chitosan-based buccal mucoadhesive patches to enhance the systemic bioavailability of tizanidine.

Tizanidine hydrochloride (TZN) is a muscle relaxant used to treat a variety of disorders such as painful muscle spasms and chronic spasticity. TZN has low oral bioavailability due to extensive first-pass metabolism and is used orally at a dose of 6-24 mg per day. In the present study, buccal patches were prepared by solvent casting method using chitosan glutamate (Chi-Glu) and novel chitosan azelate (Chi-Aze) which was synthesised in-house for the first time, to enhance the bioavailability of TZN by bypassing first-pass metabolism. The characterisation, mucoadhesion and drug release studies were performed. Chi-Aze patches retained their integrity longer in the buccal medium and showed higher ex vivo drug permeability compared to that prepared with Chi-Glu. In vivo studies revealed that buccal formulation fabricated with Chi-Aze (3%) showed approx 3 times more bioavailability than the orally administered commercial product. Results of the studies indicate that Chi-Aze, prepared by conjugation of chitosan and a fatty acid, the patch formulation is a promising buccal mucoadhesive system due to the physical stability in buccal medium, the good mucoadhesiveness and the high TZN bioavailability. Moreover, Chi-Aze patch might be an alternative to oral formulations of TZN to reduce the dose and frequency of drug administration.

Development and Evaluation of Combined Effect Buccal Films for Treatment of Oral Candidiasis.

Buccal film formulations, including antifungal nystatin, anti-inflammatory agent hydrocortisone acetate, and local anesthetic lidocaine hydrochloride for pain relief, were developed. Bioadhesive films were fabricated with hydrophilic polymers, hydroxyethyl cellulose (HEC), and xanthan gum (XG) and dried in the incubator. Textural, swelling, and bioadhesive properties, physicochemical and in vitro release characteristics, and antifungal activities of bioadhesive films were evaluated.Bioadhesive films significantly extended nystatin release by prolonging retention time of the target area formulation while rapidly releasing hydrocortisone acetate and lidocaine HCl, reducing drug administration. The polymer type affected bioadhesion strength and erosion ratio, and XG formulations had more polymer suitability. Consequently, XT-O2 formulation that was prepared with xanthan gum and tween 80, was best for its highest antifungal film activity (20.00 ± 0.07 mm), released nystatin (44.296% ± 1.695), and lowest erosion matrix (36.719% ± 0.249). The selected formulation can be used for compatibility, stability and in vivo studies targeted oral candidiasis infections.

Oxytocin-loaded sustained-release hydrogel graft provides accelerated bone formation: An experimental rat study.

Restoration of the lost bone volume is one of the most deliberate issues in dentistry. Sustained-release microspherical oxytocin hormone in a poloxamer hydrogel scaffold combined with a mixture of ß-tricalcium phosphate and hydroxyapatite (CP) may serve as a suitable bone graft. The aim of this study was to design and test a novel thermosensitive hydrogel graft incorporating oxytocin-loaded poly(d, l-lactide-co-glycolide) (PLGA) sustained-release microspheres and CP. Thermosensitive poloxamer hydrogel containing CP (HCP graft) was prepared as a base and combined with hollow microspheres (HCPM) and oxytocin-loaded microspheres (HCPOM). Eighty Wistar rats were used for testing the grafts and a control group in 8-mm-diameter critical-sized calvarial defects (CSD); (n = 20). Bone healing at the 4th and 8th weeks was evaluated by histological, histomorphometric, and radiological (micro-computed tomography [µCT]) analyses. The results were analyzed by two-way analysis of variance (P < .05). Oxytocin-loaded PLGA microspheres prepared by the solvent displacement method yielded a high encapsulation efficiency of 89.5% and a slow drug release. Incorporation of the microspheres into the hydrogel graft slowed the release rate down and the release completed within 32 days. HCPOM revealed the highest new bone formation (26.45% ± 6.65% and 30.76% ± 4.37% at the 4th and 8th weeks, respectively; P < .0001) while HCPM and HCP groups revealed a bone formation of around 10% (P > .05). µCT findings of HCPOM group showed the highest mean bone mineral density values (42.21 ± 5.14 and 46.94 ± 3.30 g/cm3 for the 4th and 8th weeks, respectively; P < .0027). The proposed oxytocin-loaded sustained-release PLGA microspheres containing thermosensitive hydrogel graft (HCPOM) provide an accelerated bone regeneration in the rat calvaria.

The efficacy of sustained-release chitosan microspheres containing recombinant human parathyroid hormone on MRONJ.

Treatment of patients with bisphosphonate usage is a significant concern for oral surgeons because it interferes with jaw bone turnover and regeneration. In case of adverse effects manifesting related to bisphosphonate use, oral surgeons are usually treating and keep the patient's symptoms under control. In this study, we aimed to investigate a new treatment protocol for medication-related osteonecrosis of the jaw (MRONJ). This treatment protocol consisted of administering human parathyroid hormone (hPTH) loaded chitosan microspheres which were prepared by ionotropic gelation method or/and the prepared microspheres were suspended in a poloxamer gel. After in-vitro optimization studies, the efficacy of the chosen formulations was evaluated in-vivo studies. Zoledronic acid was administered daily to forty-eight adult female Sprague-Dawley rats, divided into four experimental groups, at a daily concentration of 0.11 mg/kg over three weeks to induce the MRONJ model. At the end of this period, maxillary left molar teeth were extracted. In the first group, the subjects received no treatment. In the negative control group, poloxamer hydrogel containing empty microspheres were immediately applied to the soft tissues surrounding the extraction socket. The treatment group-1 was treated with local injections of poloxamer hydrogel containing hPTH. The treatment group-2 was treated with a single local injection of poloxamer hydrogel containing hPTH-loaded chitosan microspheres. Both treatment groups received a total of 7 µg of hPTH at the end of the treatment protocol. Our study demonstrates successful attenuation of MRONJ through a local drug delivery system combined with hPTH, as opposed to previously attempted treatment strategies.

Modified chitosan-based nanoadjuvants enhance immunogenicity of protein antigens after mucosal vaccination.

Nasal vaccination is considered to be an effective and convenient way of increasing immune responses both systemically and locally. Although various nanovaccine carriers have been introduced as potential immune adjuvants, further improvements are still needed before they can be taken to clinical usage. Chitosan-based nanovaccine carriers are one of the most widely studiedadjuvants, owing to the abilityof chitosan toopen tight junctions between nasal epithelial cells and enhance particle uptake as well as its inherent immune activating role. In present study, bovine serum albumin (BSA) loaded nanoparticles were prepared using novel aminated (aChi) and aminated plus thiolated chitosan (atChi) polymers, to further enhance mucoadhesiveness and adjuvanticity of the vaccine system by improving electrostatic interactions of polymers with negatively charged glycoproteins. Nanocarriers with optimum size and surface charge, high encapsulation efficiency of model antigen and good stability were developed. Negligible toxicity was observed in Calu-3 and A549 cell lines. In vivo studies, revealed high levels of systemic antibodies (IgG, IgG1 and IgG2a) throughout the study and presence of sIgA in vaginal washes showed that common mucosal system was successfully stimulated. Cytokine levels indicated a mixed Th1/Th2 immune response. A shift towards cellular immune responses was observed after nasal immunisation with antigen loaded nanoparticle formulations. These nanoparticles exhibit great potential for nasal application of vaccines.

An alternative approach to wound healing field; new composite films from natural polymers for mupirocin dermal delivery.

In this study, novel adhesive films were prepared for Mupirocin dermal delivery. Natural polymers as chitosan, sodium alginate and carbopol were used for films development to evaluate possible interactions and drug release properties. Solvent evaporation method was used for films preparation. Preliminary studies involved FT-IR spectroscopy and Scanning Electron Microscopy to specify interactions and morphology. Thickness, tensile strength and water uptake in phosphate buffer saline were evaluated whereas in vitro release studies were also performed. In vitro drug release studies demonstrated that mupirocin release was improved. Ex vivo bioadhesion and permeation studies using Balb-c mice were performed to check the suitability of the films. Antimicrobial ability was evaluated by agar well diffusion tests. Finally, excisional wound model applied to test the wound healing effect and evaluated macroscopic and histopathologically. One formulation was found more effective compared to the market product for wound healing at Balb-c mice.

Effect of the linear aliphatic amine functionalization on in vitro transfection efficiency of chitosan nanoparticles.

The aim of this study is to prepare the long linear aliphatic amine pendant group-functionalized chitosan based nanoparticulate gene carrier system with improved properties for the efficient transfection. The amine functionalized chitosan (MChi) was synthesized by using N-(2-hydroxyethyl)ethylenediamine (HE-EDA) and characterized for the first time. The nanoparticles of MChi (nMChi) were prepared by ionic gelation method, and their particle size, polydispersity (PDI), zeta potential (mV), gene binding capacity and cytotoxicity were determined. Green Fluorescent Protein circular plasmid DNA (pEGFN1) loaded nanoparticles (gnMChi) were used in the transfection studies. The results showed that nMChi with a particle size of 102.9 nm and zeta potential of 41.9 ± 5.63 mV was non-toxic, had high transfection efficiency in Human Embryonic Kidney 293 and Primary Ovine Fibroblast cell lines and would be used as an efficient gene carrier system.

The efficacy of sustained-release chitosan microspheres containing recombinant human parathyroid hormone on MRONJ

Abstract Treatment of patients with bisphosphonate usage is a significant concern for oral surgeons because it interferes with jaw bone turnover and regeneration. In case of adverse effects manifesting related to bisphosphonate use, oral surgeons are usually treating and keep the patient's symptoms under control. In this study, we aimed to investigate a new treatment protocol for medication-related osteonecrosis of the jaw (MRONJ). This treatment protocol consisted of administering human parathyroid hormone (hPTH) loaded chitosan microspheres which were prepared by ionotropic gelation method or/and the prepared microspheres were suspended in a poloxamer gel. After in-vitro optimization studies, the efficacy of the chosen formulations was evaluated in-vivo studies. Zoledronic acid was administered daily to forty-eight adult female Sprague-Dawley rats, divided into four experimental groups, at a daily concentration of 0.11 mg/kg over three weeks to induce the MRONJ model. At the end of this period, maxillary left molar teeth were extracted. In the first group, the subjects received no treatment. In the negative control group, poloxamer hydrogel containing empty microspheres were immediately applied to the soft tissues surrounding the extraction socket. The treatment group-1 was treated with local injections of poloxamer hydrogel containing hPTH. The treatment group-2 was treated with a single local injection of poloxamer hydrogel containing hPTH-loaded chitosan microspheres. Both treatment groups received a total of 7 µg of hPTH at the end of the treatment protocol. Our study demonstrates successful attenuation of MRONJ through a local drug delivery system combined with hPTH, as opposed to previously attempted treatment strategies.

Preparation and Characterization of Doripenem-Loaded Microparticles for Pulmonary Delivery.

Background: Pneumonia is a bacterial lower respiratory tract infection that has a high morbidity rate. The gram-negative pathogen Pseudomonas aeruginosa is a significant cause of nosocomial infections and ventilator-associated pneumonias and is mainly treated by carbapenems. Doripenem is a carbapenem drug, which has a broad-spectrum antibacterial activity. The aim of this study was to develop doripenem-loaded chitosan microparticles for pulmonary administration to provide more efficient treatment for pneumonia. Methods: Ionotropic gelation and the spray-drying method were used to obtain doripenem-loaded chitosan microparticles with different lactose, trehalose, and L-leucine concentrations. Physicochemical characteristics, in vitro drug release properties, and aerodynamics properties were investigated and in vitro antimicrobial susceptibility tests of the formulations were performed. Assessment of aerodynamic properties of the powders, including Mass Median Aerodynamic Diameter, size distribution, and fine particle fraction (FPF), were performed using a Next Generation Impactor. Cytotoxicity of the fabricated microparticles was assessed using the Calu-3 cell airway epithelial cell line. Results: Optimum microparticles were produced using a combination of ionotropic gelation and spray-drying methods. Spray-dried microparticle production yield was relatively high (74.03% ± 3.88% to 98.23% ± 1.70%). Lactose, trehalose, and L-leucine were added to the formulation to prevent aggregation produced by the ionotropic gelation spray-drying method. Each formulation's encapsulation efficiency was above 78.98% ± 2.37%. The doripenem-loaded microparticle mean diameter ranged from 3.8 ± 0.110 to 6.9 ± 0.090 µm. Microparticles with 20% (w/w) L-leucine had the highest FPF ratio indicating the best aerosolization properties of the formulations. The efficacy of the formulations as an antibacterial agent was increased by forming doripenem-loaded microparticles compared to blank microparticles. P. aeruginosa showed the same susceptibility to all doripenem-loaded microparticle formulations. Cell viability of microparticles was between 70% ± 0.08% and 90% ± 0.04% at 0.5 and 10 mg/mL concentration, respectively. Conclusions: Doripenem-loaded microparticles, produced using a combination of ionotropic gelation and spray-drying methods, are suitable for pulmonary drug delivery based on their particles size, zeta potential, cytotoxicity and high production yield. To our knowledge, this is the first study that microparticles containing doripenem were produced and characterized.

Combined effect of parathyroid hormone and strontium ranelate on bone healing in ovariectomized rats.

OBJECTIVE: Parathyroid hormone (PTH) enhances bone healing. Strontium ranelate (SR) is an antiresorptive agent that increases bone formation. Reports about combined effects of PTH and SR on local bone regeneration in osteoporotic subjects are limited. We aimed at investigating the efficacy of PTH and SR for promoting new bone formation in critical-sized defects of ovariectomized rats. MATERIALS AND METHODS: Parathyroid hormone- and/or SR-containing poloxamer implant tablets with/without chitosan microparticles were delivered locally to calvarial defects of 90 Wistar rats. Biopsies were analyzed histologically and histomorphometrically at 4 and 8 weeks of healing. RESULTS: Histomorphometry revealed that PTH alone promoted new bone formation at 4 weeks but the efficiency declined in 8 weeks. There was no positive effect of SR alone on bone formation at 4 or 8 weeks. Calvarial defects treated with PTH+SR combinations showed statistically significant greater new bone formation than either treatment alone at both time intervals. Tissue responses were modest and supported the good biocompatibility of the biomaterials used. CONCLUSION: Parathyroid hormone and SR combinations can be effective for calvarial bone regeneration of ovariectomized rats. PTH plus SR may have potential use as bone graft material in orthopedic and dental surgery to enhance bone healing and osseointegration.

Nasal vaccination with poly(ß-amino ester)-poly(d,l-lactide-co-glycolide) hybrid nanoparticles.

Mucosal vaccination stimulates both mucosal and systemic immunity. However, mucosal applications of vaccine antigens in their free form generally result in poor systemic immune responses and need adjuvantation. In this study, bovine serum albumin loaded, new hybridised poly(ß-amino ester)-poly(d,l-lactide-co-glycolide) nanoparticles were prepared by double emulsion-solvent evaporation method, characterised and evaluated in vivo as nasal vaccine carriers. Cationic spherical particles with a mean size of 240nm, good physical stability and high encapsulation efficiency were obtained. Protein structure was not affected throughout preparation and minimal toxicity was shown in Calu-3 and A549 cells. Nasal vaccination with these nanoparticles revealed markedly higher humoral immune responses compared with free antigen following intranasal and subcutaneous immunisation. Mucosal immune response was also stimulated and cytokine titres indicated that Th1 and Th2 pathways were successfully activated. This study shows that the formulated hybrid nanoparticles can be a promising carrier for nasal immunisation of poor antigenic proteins.

The effects of the thiolation with thioglycolic acid and l-cysteine on the mucoadhesion properties of the starch-graft-poly(acrylic acid).

The aim of this study is to investigate the effects of the thiolation on the mucoadhesion characteristics of the gelatinized and crosslinked wheat starch-graft-poly(acrylic acid) [(WS-g-PAA)gc] for potential use in drug delivery via vaginal route. Thiolation of (WS-g-PAA)gc was first time realized using l-cysteine hydrochloride monohydrate (CyS) and thioglycolic acid (TGA). These conjugates [(WS-g-PAA)gcth] were characterized using FTIR. The free SH group, mucoadhesion, cytotoxicity characteristics and the mechanism of the thiolation were also evaluated. To obtain fundamental data for possible application such as drug carrier, in vitro and in vivo progesterone release profiles from the mucoadhesive tablet formulations were also determined. The results showed that, vaginal tablet containing (WS-g-PAA)gc-TGA, which has not contain free SH groups in its structure, displays higher mucoadhesion than (WS-g-PAA)gc and (WS-g-PAA)gc-CyS. This tablet formulation can also be used as a drug carrier in vaginal applications.

Development of starch based mucoadhesive vaginal drug delivery systems for application in veterinary medicine.

The aim of this study was to prepare and evaluate the mucoadhesive, biocompatible and biodegradable progesterone containing vaginal tablets based on modified starch copolymers for the estrus synchronization of ewes. Starch-graft-poly(acrylic acid) copolymers (S-g-PAA) were synthesized and characterized. The vaginal tablets were fabricated with S-g-PAA and their equilibrium swelling degree (Qe) and matrix erosion (ME%) were determined in lactate buffer solution. In vitro, mucoadhesive properties of the tablets were investigated by using ewe vaginal mucosa and in vivo residence time were also investigated. In vitro and in vivo progesterone release profiles from the tablets were compared with two commercial products. Tablet formulation containing wheat starch based grafted copolymer (WS-g-PAA)gc indicated promising results and might be convenient as an alternative product to the commercial products in veterinary medicine.

Development of chitosan-pullulan composite nanoparticles for nasal delivery of vaccines: optimisation and cellular studies.

Nasal immunisation with nanoparticles has already shown promising results. In this study, nanoparticle composites carrying BSA for nasal vaccination prepared using electrostatic interaction process between polycation N-trimethyl chitosan chloride (TMC), chitosan glutamate (CG), chitosan chloride (CCl) and polyanion carboxymethyl pullulan (CMP). A mass ratio of 2:1 for TMC-CMP combination produced stable nanocarriers. For CCl-CMP and CG-CMP formulations needed a mass ratio of 3:1. Loading efficiency was >90% for all formulations. Nanoparticles' size ranged from 207 to 603 nm. The surface charge of the complexes varied between +14 and +33 mV. SDS-PAGE integrity of the model antigen was also demonstrated. MTT studies showed that nanoparticle composites were less toxic to Calu-3 cells than the particles of cationic polymers alone. FITC-BSA loaded nanoparticles efficiently taken up by J774A.1 macrophages as confirmed by confocal microscopy highlighting the potential of these novel nanoparticulate carriers' use for nasal vaccination.

Development of chitosan-pullulan composite nanoparticles for nasal delivery of vaccines: in vivo studies.

Here, we aimed at developing chitosan/pullulan composite nanoparticles and testing their potential as novel systems for the nasal delivery of diphtheria toxoid (DT). All the chitosan derivatives [N-trimethyl (TMC), chloride and glutamate] and carboxymethyl pullulan (CMP) were synthesised and antigen-loaded composites were prepared by polyion complexation of chitosan and pullulan derivatives (particle size: 239-405 nm; surface charge: +18 and +27 mV). Their immunological effects after intranasal administration to mice were compared to intramuscular route. Composite nanoparticles induced higher levels of IgG responses than particles formed with chitosan derivative and antigen. Nasally administered TMC-pullulan composites showed higher DT serum IgG titre when compared with the other composites. Co-encapsulation of CpG ODN within TMC-CMP-DT nanoparticles resulted in a balanced Th1/Th2 response. TMC/pullulan composite nanoparticles also induced highest cytokine levels compared to those of chitosan salts. These findings demonstrated that TMC-CMP-DT composite nanoparticles are promising delivery system for nasal vaccination.

Bioadhesive tablets containing cyclodextrin complex of itraconazole for the treatment of vaginal candidiasis.

Itraconazole (ITR) is commonly used in the treatment of Candida infections. It has a nephrotoxic effect and low bioavailability in patients who suffer from renal insufficiency, and its poor solubility in water makes ITR largely unavailable. Cyclodextrins (CyDs) are used to form inclusion complexes with drugs to improve their aqueous solubility and to reduce their side effects. In this study, ITR was complexed with γ-cyclodextrin (γ-CyD), hydroxypropyl-ß-cyclodextrin (HP-ß-CyD), methyl-ß-cyclodextrin (Met-ß-CyD) and sulphobutyl ether-ß-cyclodextrin (SBE7-ß-CyD) to increase its water solubility and to reduce the side effects of the drug without decreasing antifungal activity. Complex formation between ITR and CyDs was evaluated using SEM, (1)H NMR and XRD studies. The antifungal activity of the complexes was analyzed on Candida albicans strains, and the susceptibility of the strains was found to be higher for the ITR-SBE7-ß-CyD complex than for the complexes that were prepared with other CyDs. Vaginal bioadhesive sustained release tablet formulations were developed using the ITR-SBE7-ß-CyD inclusion complex to increase the residence time of ITR in the vagina, thereby boosting the efficacy of the treatment. The swelling, matrix erosion and bioadhesion properties of formulations and the drug release rate of these tablets were analyzed, and the most therapeutically effective vaginal formulation was determined.

Design and evaluation of polysaccharide-based transdermal films for the controlled delivery of nifedipine.

It was aimed to develop the matrix type polysaccharide-based transdermal films of nifedipine (NFD) to provide its long term plasma concentration. The mechanical tests were carried out on gel formulations which were utilised in the fabrication of transdermal films to determine the type of polymer (pectin, sodium alginate) and plasticizer (propylene glycol, glycerine) as well as their concentrations. The mechanical strength, elasticity, bioadhesiveness and the drug release characteristics of optimised films containing NFD were evaluated. Permeation of NFD from the films with/without adding an enhancer (nerolidol) was followed through excised rat skin using Franz diffusion cells. Results showed that the gels composed of either pectin or sodium alginate were appropriate for the fabrication of transdermal films of NFD, and the addition of propylene glycol improved mechanical strength, flexibility, and bioadhesiveness of the films. Permeation data showed that nerolidol was an effective permeation enhancer for the polysaccharide-based transdermal films of NFD.

Topical drug delivery using chitosan nano- and microparticles.

INTRODUCTION: Topical drug delivery offers important benefits for improving the therapeutic effect and reducing systemic side effects of the administered compounds. In addition, utilization of biopolymeric material-based systems can play a key role in developing new topical dosage forms and their applications. This review describes the advances that have been made, new strategies and as well as possible challenges of particular systems of chitosan used in topical drug delivery, including challenging innovations in topical usage of these systems that can make significant impact on clinical practice. AREAS COVERED: The main area covered is hypothesis that particulate carriers based on chitosan and its derivatives can penetrate the topical barriers from the body. For this reason, the novel studies described emphasize the fact that chitosan-based particular systems are popular that can be tailor-made according to in vitro and in vivo characterization. Such parameters, which are known to influence their in vivo performance, can be modulated by adjusting the formulation conditions of the chitosan-based particular systems for topical application. EXPERT OPINION: The topical application of drugs with particulate systems comprising a natural polymer, chitosan, is one of the most popular drug delivery routes. The aim of topical use of chitosan particles is to improve the drug bioavailability by prolonging the residence time of drugs applied topically or by enhancing the passing of drugs through the epithelial cells by opening the tight junctions between epithelial cells and also to reduce the side effects of the drugs.