Cellulosic Textiles-An Appealing Trend for Different Pharmaceutical Applications.

Cellulose, the most abundant biopolymer in nature, is derived from various sources. The production of pharmaceutical textiles based on cellulose represents a growing sector. In medicated textiles, textile and pharmaceutical sciences are integrated to develop new healthcare approaches aiming to improve patient compliance. Through the possibility of cellulose functionalization, pharmaceutical textiles can broaden the applications of cellulose in the biomedical field. This narrative review aims to illustrate both the methods of extraction and preparation of cellulose fibers, with a particular focus on nanocellulose, and diverse pharmaceutical applications like tissue restoration and antimicrobial, antiviral, and wound healing applications. Additionally, the merging between fabricated cellulosic textiles with drugs, metal nanoparticles, and plant-derived and synthetic materials are also illustrated. Moreover, new emerging technologies and the use of smart medicated textiles (3D and 4D cellulosic textiles) are not far from those within the review scope. In each section, the review outlines some of the limitations in the use of cellulose textiles, indicating scientific research that provides significant contributions to overcome them. This review also points out the faced challenges and possible solutions in a trial to present an overview on all issues related to the use of cellulose for the production of pharmaceutical textiles.

Novel naringin tablet formulations of agro-resides based nano/micro crystalline cellulose with neuroprotective and Alzheimer ameliorative potentials.

This study aimed to prepare micro/nanocrystalline cellulose-loaded naringin (NAR) tablets and evaluate their neuro-protective/therapeutic potentials in Alzheimer's disease (AD) model. Micro/nanocellulose was prepared from different agro-wastes, and the different cellulose preparations were then used to formulate eight oral tablets of naringin micro/nanoparticles by direct compression. AD-like symptoms were induced in adult male Sprague Dawley rats by co-administration of 150 mg/kg AlCl3 and 300 mg/kg D-galactose (oral administration/one week), and NAR tablets were assessed for neuroprotective/therapeutic potentials in terms of behavioral changes, levels of neurodegenerative and inflammatory markers, brain redox status, neurotransmitter tones, and cortex/hippocampus histopathological alterations. NAR treatments have significantly reversed the neurotoxic effect of AlCl3 as demonstrated by improved spatial and cognitive memory functions and promoted antioxidant defense mechanisms in treated AD animals. Also, the neurodegeneration was markedly restrained as reflected by marked histopathological enhancement, and prevention/amelioration of neuropsychiatric disorders, besides the restorative effect on dysregulated neurotransmitters tone. Both NAR tablet forms showed an overall higher ameliorative effect compared to the DPZ reference drug. The formulated tablets represent promising neuroprotective/therapeutic agents for Alzheimer's disease.

Micellar buccal film for safe and effective control of seizures: Preparation, in vitro characterization, ex vivo permeation studies and in vivo assessment.

The current research article focused on formulating an easily applied, water-based buccal film loaded with the antiepileptic drug, lamotrigine (LTG). The designed film can be comfortably administered by epileptic patients to ensure a controllable therapeutic efficacy against seizures. The solubility of LTG in water was significantly improved by micellar solubilization. Upon testing several surfactants, three of them (Synperonic PE/P84, Brij L23, and Brij 78) achieved maximum possible solubility for LTG and were characterized for their micellar size, cloud point, and % transmittance. Selected micellar systems were incorporated within a buccal film prepared using solvent casting method based on either gelatin or polyvinylpyrrolidone (3%w/v) with 1.5%w/v propylene glycol as a plasticizer. Different micellar films were characterized for their physicochemical characteristics, swelling index, folding endurance, drug content uniformity, and in vitro LTG release. From the tested formulations, one formulation; LTG-BF1 (in which Brij 78 was used for the micellar solubilization and gelatin as the matrix former), was selected as the optimum and extensively studied for mucoadhesion, ex vivo permeation studies by Franz diffusion cells and confocal laser scanning microscopy. Results showed superior enhanced permeation of micellar film. LTG-BF1 was evaluated for the in vivo performance using rats. Status epilepticus was induced in rats by injecting Pentylenetetrazol (PTZ) i.p. at an initial dose of 30 mg/kg, followed by 10 mg/kg every10 min till 60 min. A group of rats receiving the designed buccal formulation (20 mg/kg) was compared with a group receiving the same dose of the oral market product and the normal control and PTZ groups. Rats receiving LTG-BF1 recorded reduced seizure scores at all stages, longer latency time, and higher threshold PTZ dose compared to PTZ and market product groups. In addition, LTG-BF1 reduced brain concentrations of TNF-α and TGF-ß with an elevation of EAAT2 and GABA brain contents compared to PTZ and market product groups and ameliorated neuronal damage. In conclusion, LTG-loaded buccal micellar film proved a superior antiepileptic effect in PTZ induced acute epileptic model.

An in vitro / in vivo release test of risedronate drug loaded nano-bioactive glass composite scaffolds.

Three-dimensional (3D) matrices scaffolds play a noteworthy role in promoting cell generation and propagation. In this study, scaffolds prepared from chitosan/polyvinyl alcohol loaded with/without an osteoporotic drug (risedronate) and nano-bioactive glass (nBG) have been developed to promote healing of bone defects. The scaffolds were characterized by scanning electron microscopy (SEM), porosity test as well as mechanical strength. The pattern of drug release and ability to promote the proliferation of Saos-2osteosarcoma cells had also been reported. Osteogenic potential of the scaffolds was evaluated by testing their effect on healing critical-sized dog's mandibular bone defects. Increasing chitosan and nBG in the porous scaffolds induced decrease in drug release, increased the scaffold's strength and supported their cell proliferation, alkaline phosphatase (ALP) activities, as well as increased calcium deposition. Histological and histomorphometric results demonstrated newly formed bone trabeculae inside critical-sized mandibular defects when treated with scaffolds. Trabecular thickness, bone volume/tissue volume and the percentage of mature collagen fibers increased in groups treated with scaffolds loaded with 10% nBG and risedronate or loaded with 30% nBG with/without risedronate compared with those treated with non-loaded scaffolds and empty control groups. These findings confirmed the potential osteogenic activity of chitosan/polyvinyl alcohol-based scaffolds loaded with risedronate and nBG.

Efficient drug delivery vehicles of environmentally benign nano-fibers comprising bioactive glass/chitosan/polyvinyl alcohol composites.

Nano-fiber composites have shown promising potential in biomedical and biotechnological applications. Herein, novel nano-fiber composites constituting a blend of polyvinyl alcohol (PVA) and chitosan (CS) along with different weight ratios of nano-bioactive glass (BG) were prepared by electrospinning. Nano-fibers incorporating 10% (by wt.) of BG were uniform, dense and defect-free with a diameter of 20-125 nm. The model osteoporotic drug (Risedronate sodium) was blended with the electrospinning forming solution and the in-vitro drug release was further studied. About 30% of the drug was released after only 30 min and the release pattern was sustained over 96 h. Drug release took place through a two-stage intra-particle diffusion mechanism. BG-incorporated nano-fibers markedly retarded the drug release profile relative to their BG-free counterparts. They also enhanced the drug release efficiency by releasing 93 ± 4% of the drug. The developed nano-fiber composites can be potentially used as drug-delivery vehicles due to their efficiency and sustained drug release capacity.

Development of tizanidine loaded aspasomes as transdermal delivery system: ex-vivo and in-vivo evaluation.

New generation of amphiphilic vesicles known as aspasomes were investigated as potential carriers for transdermal delivery of tizanidine (TZN). Using full factorial design, an optimal formulation was developed by evaluating the effects of selected variables on the properties of the vesicles with regards to entrapment efficiency, vesicle size and cumulative percentage released. The optimal formula (TZN-AS 6) consisting of 20 mg TZN, 50 mg ascorbyl palmitate (AP), 50 mg cholesterol (CH) and 50 mg Span 60, represented well dispersed spherical vesicles in the nanorange sizes and exhibited excellent stability under different storage conditions. Ex-vivo permeation studies using excised rat skin showed a 4.4-fold increase of the steady state flux in comparison to the unformulated drug (p < 0.05). The pharmacokinetic parameters obtained from the in-vivo study using Wistar rats, showed that the bioavailability of TZN was enhanced significantly (p < 0.05) when compared to the oral market product of TZN, Sirdalud®. Moreover, skin irritancy tests confirmed that the vesicles were non-invasive and safe for the skin. Based on the results obtained, the optimised aspasomes formula represents a promising Nano platform for TZN to be administered transdermally, thus improving the therapeutic efficacy of this important muscle relaxant.

Soluplus® based solid dispersion as fast disintegrating tablets: a combined experimental approach for enhancing the dissolution and antiulcer efficacy of famotidine.

Famotidine (FM) is considered among the first-line therapy for treatment of gastric ulcers; however, its poor aqueous solubility resulted in low bioavailability and limited therapeutic efficacy. Therefore, fast disintegrating tablet (FDT) incorporating FM solid dispersion was developed in a combined formulation approach for efficient treatment of ulcers. Within the investigated polymers, solid dispersions were prepared using the novel copolymer, Soluplus® (SP) by kneading and freeze-drying techniques at various FM:SP ratios. FM solid dispersion prepared at 1:10 ratio using freeze drying (FM-SP10) manifested the highest saturation solubility, having smooth porous surface with the complete conversion of FM to the amorphous form. FDTs of FM-SP10 was produced by direct compression using three ready-to-use excipients; F-melt, Pearlitol Flash, and Fujicalin. All tablets showed adequate thickness, diameter, weight variation, drug content, and friability (<1%). Fujicalin-FDTs (FM-FDT-FU) exhibited the shortest disintegration time with almost complete dissolution of the drug (>95%) within 30 min. It also revealed remarkable antiulcerogenic effect on ethanol induced gastric ulcers in terms of ulcer and protection indices compared to the market product. Pretreated rats with FM-FDT-FU demonstrated normal gastric area with the absence of edema and leucocytes infiltration, supported by the histological examination. FM-FDT-FU administration protected the stomach from oxidative damage and severe inflammatory response via the significant increase of glutathione level and the decreased levels of nitric oxide, interleukin and cyclooxygenase. Thus, the present study provides a promising dosage form of FM characterized by superior antiulcerogenic potential with desired tableting properties.

Comparative study of liposomes, ethosomes and transfersomes as carriers for enhancing the transdermal delivery of diflunisal: In vitro and in vivo evaluation.

The current study aimed to develop an effective transdermal nanovesicular carrier of diflunisal that provides enhanced delivery through the skin. Two types of nanovesicles, ethosomes and transfersomes, were investigated and compared to conventional liposomes. Ethosomes with variable ethanol contents (10, 30 and 50%) and transfersomes using different edge activators, including sodium deoxycholate, sodium cholate and sodium taurocholate, were prepared and characterized. The obtained vesicles revealed good entrapment efficiencies (46.73-65.99%), nanometric vesicle sizes (453.10-796.80 nm) and negative zeta potential values (-45.40 to -86.90 mV). Ethosomes with 30% ethanol and sodium deoxycholate-containing transfersomes were incorporated into hydrogels to evaluate their in vitro release and permeation patterns. Nanovesicular hydrogels exhibited more sustained diflunisal release than did corresponding dispersions. Compared to liposomal hydrogel, both carriers proved the superiority of diflunisal permeation and flux across the skin. Confocal laser scanning microscopy showed improved penetration of rhodamine-loaded nanovesicles through skin layers with a wider distribution and higher fluorescence intensity. Compared to liposomes, selected nanovesicles exhibited remarkable antinociceptive and anti-inflammatory effects manifested by significant reduction in number of writhings and significantly higher inhibition of paw oedema. Hence, the developed nanovesicles could be considered promising carriers for transdermal delivery of diflunisal for pain and inflammation management.

Evaluation of bilosomes as nanocarriers for transdermal delivery of tizanidine hydrochloride: in vitro and ex vivo optimization.

Bilosomes were developed in order to investigate their efficacy as nanocarriers for transdermal delivery of Tizanidine HCl (TZN), a skeletal muscle relaxant with low oral bioavailability. Full factorial experimental design consisting of 27 combinations was generated to study the effects of surfactant type, surfactant-to-cholesterol ratio and the amount of bile salt on the entrapment efficiency (EE), the vesicle size (VS) and in vitro dissolution of the TZN-loaded bilosomes. The permeation through the stratum cornea was optimized with the vertical diffusion assembly using excised rat skin. The permeation parameters of the selected bilosomes were compared to the unformulated drug and it was shown that TZN-B24 exhibited the highest enhancement ratio (ER = 8.8).The optimal formula (TZN-B24) consisting of span 60 in a ratio with cholesterol of 1:1 and 20 mg of bile salt was obtained by employing the desirability function of Design-Expert® software. The mathematical model used for the optimization was validated by comparing the predicted values of the EE (82.3%) and the VS (165.8 nm) with the experimental values of EE = 84.42% and of VS = 161.95 nm. TZN-B24 displayed high zeta potential which contributed to its good stability. It was evident from the results of this study that incorporating TZN in bilosomes improved significantly its permeation through the skin barrier and thus bilosomes can offer a potential nanoplatform using the transdermal route to improve the bioavailability of the drug.

A potential antibacterial wound dressing of cefadroxil chitosan nanoparticles in situ gel: Fabrication, in vitro optimization and in vivo evaluation.

Wound healing following skin injury is a natural phenomenon that usually lacks quality, rapidity, and aesthetics. Thus, the purpose of this study was to fabricate a new easily applied in situ gel of cefadroxil (CDX) loaded chitosan nanoparticles (CDX-CSNPs) that could promote wound healing, capable of inhibiting the possible accompanying bacterial infection. The nanoparticles were prepared by double emulsion technique and the influence of formulation parameters on drug entrapment efficiency (EE%), particle size (PS), polydispersity index (PDI) and zeta potential (ZP) were investigated using a full factorial design. The results show that the optimized CDX-CSNP1 composed of low molecular weight chitosan (0.2%w/v) was spherical with EE%, PS, PDI and ZP of 84.25 ±â€¯0.02, 408.30 ±â€¯53.17 nm, 0.458 ±â€¯0.048 and 22.80 ±â€¯0.57 mV, respectively. DSC and XRD studies confirmed the amorphous nature of the drug. After ensuring the safety and non toxicity of CDX-CSNP1 in situ gel through cytotoxic study, the antibacterial activity was evaluated using a rat skin infection model against Staphylococcus aureus. Compared to the rats treated with free CDX, the CDX-CSNP1 treated group revealed a remarkable accelerated wound healing process and bacterial clearance which was further confirmed by the histopathological examination of skin biopsies.

Chitosan nanoparticles/cellulose nanocrystals nanocomposites as a carrier system for the controlled release of repaglinide.

The aim of the present work was to study the use of cellulose nanocrystals (CNC) and chitosan nanoparticles (CHNP) for developing controlled-release drug delivery system of the anti-hyperglycemic drug Repaglinide (RPG). CNC was isolated from palm fruit stalks by sulfuric acid hydrolysis; the dimensions of the isolated nanocrystals were 86-237 nm in length and 5-7 nm in width. Simple and economic method was used for the fabrication of controlled release drug delivery system from CNC and CHNP loaded with RPG drug via ionic gelation of chitosan in the presence of CNC and RPG. The prepared systems showed high drug encapsulation efficiency of about ~98%. Chemical modification of CNC by oxidation to introduce carboxylic groups on their surface (OXCNC) was also carried out for further controlling of RPG release. Particles size analysis showed that the average size of CHNP was about 197 nm while CHNP/CNC/RPG or CHNP/OXCNC/RPG nanoparticles showed average size of 215-310 nm. Compatibility studies by Fourier transform infrared (FTIR) spectroscopy showed no chemical reaction between RPG and the system's components used. By studying the drug release kinetic, all the prepared RPG formulations followed Higuchi model, indicating that the drug released by diffusion through the nanoparticles polymeric matrix.

Experimentally designed lyophilized dry emulsion tablets for enhancing the antihyperlipidemic activity of atorvastatin calcium: Preparation, in-vitro evaluation and in-vivo assessment.

This article presents the development of lyophilized orally disintegrating tablets prepared with the dry emulsion technique to enhance the in-vitro dissolution and in-vivo performance of the poorly bioavailable drug atorvastatin calcium (ATV). Tablets were fabricated by freeze-drying o/w emulsions of ATV. The Emulsions were prepared using a matrix former solution (alginate or gelatin, 2 or 4%) containing a sugar alcohol (mannitol) and a collapse protectant (glycine) as the water phase and Labrafac® as the oil phase in the presence of surfactant (synperonic® PE/P 84 or synperonic® F108) under proper homogenization. The influence of formulation parameters on friability of the prepared tablets, disintegration time and in-vitro dissolution of the drug from these tablets were investigated. Results showed the significant influence of the matrix former and emulsifier type on the disintegration time. In-vitro dissolution study revealed the enhanced dissolution rate of ATV from the lyophilized dry emulsion tablets (LDET) compared to the plain drug. DSC and XRD studies of the optimized ATV-loaded LDET proved the presence of the drug in the amorphous form. SEM images showed the intact, porous and non-collapsible structure of the prepared LDET with complete loss of ATV crystallinity. Administration of ATV-loaded LDET to high fat diet-induced hyperlipidemic rats demonstrated a significant decrease (p<0.05) in the serum and tissue levels of the tested parameters compared to the market product used. The obtained results suggest a promising, easy-to-manufacture and effective dosage form for the treatment of hyperlipidemia.

Nanotechnology as a Promising Strategy for Anticancer Drug Delivery.

BACKGROUND: Cancer was and still a very stressful and urgent disease condition representing a leading cause of death in developed as well as developing countries. Although, much research work in both medical and pharmaceutical fields has evolved in the past few years in addition to some promising clinical trials and few market products, cancer becomes much wilder, threatening and getting more lives. Most approaches have focused on the synthesis of new active ingredients or chemical modification of available ones, formulating them in suitable dosage forms aiming for targeted and effective drug delivery with minimal side effects. METHOD: Recently, application of nanotechnology through formulation of nanocarriers has acquired much more attention in treating different types of cancer tumors. Being explored in cancer therapy, nanocarriers have shown a promising capability to enhance intracellular uptake of active agents, promoting their accumulation in the tumor mass in addition to the reduction of the cellular toxicity compared to conventional chemotherapeutics. RESULTS: In view of the above findings, this review discusses recent advances in nanotechnology-based carriers for cancer drug delivery, providing detailed description of different nanocarriers from historical perspective since the first developed carrier up to the new strategies adopted to formulate novel multifunctional targeted nanocarriers for cancer therapy. CONCLUSION: The findings of this review illustrate the potential of nanotechnology-based carriers as an emerging technology for more satisfying and selective cancer therapy.

Reconstitutable spray dried ultra-fine dispersion as a robust platform for effective oral delivery of an antihyperlipidemic drug.

The current article highlights the application of spray drying technique to produce an ultra-fine powder encapsulating the antihyperlipidemic drug, atorvastatin calcium (ATV). First, ATV was dissolved in an emulsion formulation, and different carriers (pectin, alginate, chitosan HCl and hydroxypropylmethyl cellulose) in two concentrations (1.5 and 3%) were added. Then, these carrier-containing formulations were subjected to spray drying, whereby ultra-fine ATV-loaded spray dried emulsions were produced (ATV-SDE). The optimum formulation; ATV-SDE7 containing 3% w/w pectin was selected showing an obviously enhanced dissolution profile compared to the other used polymers which could be attributed to its lower ability to swell in acidic medium, resulting in faster drug diffusion into release medium. Thus, ATV-SDE7 was subjected to further characterization including; DSC, XRPD, SEM and flowability properties. In-vivo studies were conducted using high-fat induced hyperlipidemic rats. The optimum formulation depicted normal lipid profile showing significant reduction in the measured parameters at the end of daily oral treatment, compared to ATV marketed tablets and control hyperlipidemic rats confirmed by normal liver sections upon histopathological examination. The superior lipid-lowering activity of ATV-SDE7 was not only due to the enhanced dissolution of ATV but also due to the presence of pectin which is capable of lowering both cholesterol and triglyceride serum levels. Hence, the present study suggests that the formulation strategy employing ultrafine redispersible spray dried emulsion with pectin as a carrier holds a promising approach for the development of a novel dosage form of enhanced antihyperlipidemic effect for ATV.

Phospholipid complex enriched micelles: A novel drug delivery approach for promoting the antidiabetic effect of repaglinide.

To enhance the oral antidiabetic effect of repaglinide (RG), a newly emerging approach, based on the combination of phospholipid complexation and micelle techniques, was employed. Repaglinide-phospholipid complex (RG-PLC) was prepared by the solvent-evaporation method then characterized using Differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR) and X-ray powder diffraction (XPRD). The results revealed obvious disappearance of the characteristic peaks of the prepared RG-PLCs confirming the formation of drug-phospholipid complex. RG-PLC enriched micelles (RG-PLC-Ms) were prepared by the solvent-evaporation technique employing poloxamer 188 as surfactant. The prepared RG-PLC-Ms showed high drug encapsulation efficiencies (93.81-99.38%), with nanometric particle diameters (500.61-665.32nm) of monodisperse distribution and high stability (Zeta potential < -29.8mV). The in vitro release of RG from RG-PLC-Ms was pH-dependant according to the release media. A higher release pattern was reported in pH=1.2 compared to a more retarded release in pH=6.8 owing to two different kinetics of drug release. Oral antidiabetic effect of two optimized RG-PLC-M formulations was evaluated in an alloxan-induced diabetic rat model for 7-day treatment protocol. The two investigated formulations depicted normal blood glucose, serum malondialdehyde and insulin levels as well as an improved lipid profile, at the end of daily oral treatment, in contrast to RG marketed tablets implying enhanced antidiabetic effect of the drug. Hence, phospholipid-complex enriched micelles approach holds a promising potential for promoting the antidiabetic effect of RG.

Design and evaluation of proniosomes as a carrier for ocular delivery of lomefloxacin HCl.

The current investigation aims to develop and evaluate novel ocular proniosomal gels of lomefloxacin HCl (LXN); in order to improve its ocular bioavailability for the management of bacterial conjunctivitis. Proniosomes were prepared using different types of nonionic surfactants solely and as mixtures with Span 60. The formed gels were characterized for entrapment efficiency, vesicle size, and in vitro drug release. Only Span 60 was able to form stable LXN-proniosomal gel when used individually while the other surfactants formed gels only in combination with Span 60 at different ratios. The optimum proniosomal gel; P-LXN 7 (Span 60:Tween 60, 9:1) appeared as spherical shaped vesicles having high entrapment efficiency (>80%), appropriate vesicle size (187 nm) as well as controlled drug release over 12 h. Differential scanning calorimetry confirmed the amorphous nature of LXN within the vesicles. Stability study did not show any significant changes in entrapment efficiency or vesicle size after storage for 3 months at 4 °C. P-LXN 7 was found to be safe and suitable for ocular delivery as proven by the irritancy test. The antibacterial activity of P-LXN 7 evaluated using the susceptibility test and topical therapy of induced ocular conjunctivitis confirmed the enhanced antibacterial therapeutic efficacy of the LXN-proniosomal gel compared to the commercially available LXN eye drops.

Enhancement of lomefloxacin Hcl ocular efficacy via niosomal encapsulation: in vitro characterization and in vivo evaluation.

The aim of this study is to develop and evaluate niosomal dispersions loaded with the hydrophilic drug; lomefloxacin Hcl (LXN) for the management of ocular bacterial conjunctivitis. LXN-loaded niosomes were prepared by the thin film hydration method following a full factorial formulation design. Two independent variables were evaluated: the type of surfactant (X1) and the surfactant:cholesterol ratio (X2). The dependent variables comprised entrapment efficiency (EE%: Y1), particle size (PS: Y2) and zeta potential (ZP: Y3). The optimum formulation, N-LXN14 (Tw60: CH, 1:1), was spherical in shape and exhibited EE% of 68.41 ± 0.07, PS of 176.0 ± 0.98 and ZP of -40.70 ± 2.20 with a sustained release profile over 8 hours following the Higuchi model. N-LXN14 proved good physicochemical stability under refrigeration up to 3 months. Ocular irritancy test showed no signs of ocular toxicity, confirming the safety and suitability for ocular application. Microbiological evaluation of the antibacterial effect of N-LXN14 was conducted using the susceptibility test and through the induction of topical conjunctivitis by Staphylococcus aureus (S. aureus) followed by topical therapy. Susceptibility test manifested significantly higher percent inhibition of S. aureus and higher AUC0-12 h of N-LXN14 (604.59 ± 0.05) compared to the commercial product (126.25 ± 0.049). Both clinical observation and colony count of the infected eyes after eight days of treatment demonstrated significant improvement in therapeutic response. The infected eyes were completely healed with eradication of S. aureus. In conclusion, the results showed that LXN niosomal dispersions may serve as a promising superior ocular delivery system in the treatment of bacterial conjunctivitis.

Injectable nanoamorphous calcium phosphate based in situ gel systems for the treatment of periapical lesions.

Nonsurgical local treatment of a periapical lesion arising from trauma or bacterial infection is a promising innovative approach. The present study investigated the feasibility of developing injectable amorphous calcium phosphate nanoparticles (ACP NPs) and ACP NPs loaded with an anti-inflammatory drug; ibuprofen (IBU-ACP NPs) in the form of thermoreversible in situ gels to treat periapical lesions with the stimulation of bone formation. NPs were produced by a spray-drying technique. Different formulations of Poloxamer 407 were incorporated with/without the produced NPs to form injectable gels. A drug release study was carried out. A 3 month in vivo test on a dog model also was assessed. Results showed successful incorporation of the drug into the NPs of CP during spray drying. The particles had mean diameters varying from 100 to 200 nm with a narrow distribution. A drug release study demonstrated controlled IBU release from IBU-ACP NPs at a pH of 7.4 over 24 h. The gelation temperature of the injectable in situ gels based on Poloxamer 407 was measured to be 30 °C. After 3 months of implantation in dogs, the results clearly demonstrated that the inclusion of ACP NPs loaded with IBU showed high degrees of periapical bone healing and cementum layer deposition around the apical root tip.

Benzocaine loaded solid lipid nanoparticles: Formulation design, in vitro and in vivo evaluation of local anesthetic effect.

The aim of the present work is the development and evaluation of solid lipid nanoparticles (SLNs) as carrier system for topical delivery of benzocaine (BZC) improving its local anesthesia aiming to produce a fast acting and long lasting topical formulation. BZC loaded SLNs were prepared using a full factorial design to study the influence of the type of polyoxyethylene sorbitan ester surfactants as well as their concentration as independent variables on the particle size, entrapment efficacy and zeta potential selected as dependent variables. Design of experiment (DOE) and the analysis of variance (ANOVA) were conducted to assess the optimization of the developed formulations. The results indicated that the fatty acid chain length of tested surfactants and their concentration had a significant effect on the studied responses. The optimized formulations were spherical in shape of mean particle diameters<350 nm with negatively charged surface <-20mV. Particles were characterized using differential scanning calorimetry and X-ray powder diffraction confirming the amorphous nature and the uniformity of drug inclusion in the lipid matrix. Optimized BZC-SLNs were incorporated into hydrogels characterized by a pseudoplastic non-Newtonian behavior. In vitro release study revealed an apparently biphasic release process with sustained release profile following Higuchi kinetics. BZC loaded SLNs hydrogels showed more potent anesthetic effect compared to BZC hydrogel evaluated using tail-flick analgesimeter, confirming significant improvement in both the intensity and duration of anesthetic effect. The above results proved that SLNs represent good candidates to encapsulate BZC improving its therapeutic efficacy for the topical treatment of pain.

Transdermal microemulsions of Boswellia carterii Bird: formulation, characterization and in vivo evaluation of anti-inflammatory activity.

CONTEXT: Boswellia species are trees (family: Bruseraceae) found in India, Northern Africa and the Middle East. OBJECTIVE: This study aims at formulating low dose biologically active fraction from the oleogum resin of Boswellia carterii (BC) in transdermal (TD) microemulsions (MEs) to acquire promoted anti-inflammatory efficacy. MATERIALS AND METHODS: The bioactive fraction of the oleogum resin of BC was tested for solubility in different components. The most efficient were selected for constructing phase diagrams for ME preparation. The bioactive fraction was assayed by high performance liquid chromatography for 3-acetyl-11-keto-ß-boswellic acid (AKBA), at 210 nm. The bioactive fraction was incorporated in 6 MEs. ME systems were evaluated for drug content and optimized systems were tested for characterization, permeation, skin irritancy and in vivo evaluation of anti-inflammatory activity. RESULTS AND DISCUSSION: Two systems were selected; ME1 and ME4 composed of Tween 80: PEG 400 at 1:1 and 2:1 ratio, with oil content 7.78 and 17.5%, respectively. The systems showed high encapsulation efficiency >83%, small droplet size <100 nm, and suitable pH for topical application. Permeation parameters for ME1 were higher compared to ME4. Both MEs were non irritant. ME1 showed significantly higher anti-inflammatory activity versus the standard TD anti-inflammatory piroxicam. CONCLUSIONS: Optimized TD BC MEs could be used as a safe, effective and long acting alternative to oral anti-inflammatories, providing higher and prolonged efficacy and better patient compliance.