Topical delivery of mupirocin calcium nanostructured lipid carriers using a full-thickness excision wound healing model.

OBJECTIVE: Treatment of contaminated wounds represents a significant challenge in healthcare and there is a need to develop approaches maximising skin retention to maintain therapeutic concentrations of anti-infectives at the wound site. The objective of the present study was to develop and evaluate mupirocin calcium nanolipid emulgels to enhance wound healing performance and patient acceptability. METHODS: Nanostructured lipid carriers (NLCs) of mupirocin calcium were prepared by the phase inversion temperature method using Precirol ATO 5 (Gattefosse, India) and oleic acid as lipids and Kolliphor RH 40 (BASF, India) as surfactant and further incorporated into a gel base for topical delivery. RESULTS: The particle size, polydispersity index and zeta potential of mupirocin NLCs were found to be 128.8±1.25nm, 0.283±0.003 and -24.2±0.56mV, respectively. In vitro release studies from developed emulgel showed sustained drug release over 24 hours. Ex vivo drug permeation studies through excised rat abdominal skin showed better skin permeation (1712.38±15. 57µg/cm2) from developed emulgel compared to marketed ointment (827.92±21.42µg/cm2) after 8 hours, which was in agreement with in vitro antibacterial activity. Studies on Wistar rats indicated the nonirritant potential of developed emulgels. Further, mupirocin emulgels showed improved efficacy in percent wound contraction of acute contaminated open wounds in Wistar rats using a full-thickness excision wound healing model. CONCLUSION: The emulgels of mupirocin calcium NLCs appear to be effective in the treatment of contaminated wounds due to increased skin deposition and sustained release, thereby enhancing the wound healing potential of existing molecules.

A Review on Recent Advances in Mannose-Functionalized Targeted Nanocarrier Delivery Systems in Cancer and Infective Therapeutics.

Unmodified nanocarriers used in the chemotherapy of cancers and various infectious diseases exhibit prolonged blood circulation time, prevent enzymatic degradation and increase chemical stability of encapsulated therapeutics. However, off-target effect and lack of specificity associated with unmodified nanoparticles (NPs) limit their applications in the health care system. Mannose (Man) receptors with significant overexpression on antigen-presenting cells and macrophages are among the most admired targets for cancer and anti-infective therapeutics. Therefore, development of Man functionalized nanocarriers targeting Man receptors, for target specific drug delivery in the chemotherapy have been extensively studied. Present review expounds diverse Man-conjugated NPs with their potential for targeted drug delivery, improved biodistribution profiles and localization. Additionally, the review gives detailed account of the interactions of mannosylated NPs with various biological systems and their characterization not discussed in earlier published reports is discussed.

Borneol: a Promising Monoterpenoid in Enhancing Drug Delivery Across Various Physiological Barriers.

Incorporation of permeation enhancers is one of the most widely employed approaches for delivering drugs across biological membranes. Permeation enhancers aid in delivering drugs across various physiological barriers such as brain capillary endothelium, stratum corneum, corneal epithelium, and mucosal membranes that pose resistance to the entry of a majority of drugs. Borneol is a natural, plant-derived, lipophilic, volatile, bicyclic monoterpenoid belonging to the class of camphene. It has been used under the names "Bing Pian" or "Long Nao" in Traditional Chinese Medicine for more than 1000 years. Borneol has been incorporated predominantly as an adjuvant in the traditional Chinese formulations of centrally acting drugs to improve drug delivery to the brain. This background knowledge and anecdotal evidence have led to extensive research in establishing borneol as a permeation enhancer across the blood-brain barrier. Alteration in cell membrane lipid structures and modulation of multiple ATP binding cassette transporters as well as tight junction proteins are the major contributing factors to blood-brain barrier opening functions of borneol. Owing to these mechanisms of altering membrane properties, borneol has also shown promising potential to improve drug delivery across other physiological barriers as well. The current review focuses on the role of borneol as a permeation enhancer across the blood-brain barrier, mucosal barriers including nasal and gastrointestinal linings, transdermal, transcorneal, and blood optic nerve barrier.

Nanolipid Gel of an Antimycotic Drug for Treating Vulvovaginal Candidiasis-Development and Evaluation.

This paper focuses on the development and evaluation of mucoadhesive vaginal gel of fluconazole using nanolipid carriers to enhance tissue deposition in treating vulvovaginal candidiasis. Treatment of vulvovaginal candidiasis includes antimycotic agents prescribed for 1 to 7 days or longer, in relapse either orally or topically. The delivery of fluconazole as nanolipid carriers in vaginal gel can be proposed as suitable alternative to the existing conventional formulations to improve the patient acceptability, compliance and localized drug action. The nanolipid carriers of fluconazole were prepared by phase inversion temperature technique and incorporated into Carbopol 974P as gelling polymer. GRAS excipients selected and optimized were Precirol ATO 5, oleic acid and Kolliphor RH 40 to produce nanolipid dispersions. Stable nanolipid dispersions were developed using sodium dodecyl sulfate as the charge inducer. The optimized nanolipid dispersion of fluconazole had particle size, polydispersity index and zeta potential value of 158.33 ± 2.55 nm, 0.278 ± 0.003 and - 27.33 ± 0.40 mV, respectively and the average entrapment of fluconazole in the lipid carriers was found to be 67.24 ± 0.87%. The optimized vaginal gel had satisfactory mucoadhesive strength and rheological properties to facilitate vaginal application. The fluconazole release from the gel was sustained showing 30.69 ± 1.02% drug deposition in the porcine vaginal mucosa at the end of 8 h with improved antifungal activity against Candida albicans during well diffusion studies. The optimized gel was non-irritant to the vaginal mucosa of female Wistar rats with no signs of erythema or edema.

Self nanoemulsifying granules (SNEGs) of meloxicam: preparation, characterization, molecular modeling and evaluation of in vivo anti-inflammatory activity.

Meloxicam, a BCS class II drug belonging to the class of NSAIDs is indicated in conditions of rheumatoid arthritis, ankylosing spondylitis and osteoarthritis in which rapid onset of drug action is desired to reduce inflammation and pain. The objective of the study was to thus develop Self Nanoemulsifying Granules (SNEGs) of Meloxicam (MLX) for enhancement of solubility; and subsequently dissolution rate, thus aiming for a faster onset of action. Preliminary studies along with molecular modeling studies were carried out for selection of appropriate lipids, surfactants and cosurfactants for the development of MLX-loaded Self Nanoemulsifying preconcentrate (SNEP). A charge inducer was incorporated into the formulation so as to increase the solubility of MLX in lipids and hence, drug loading. A three-factor D-optimal mixture design was used for optimization of MLX loaded SNEP. The role of charge inducer in increasing the drug loading of MLX in SNEDDS was studied by molecular dynamics simulation using Desmond. Optimized SNEP was adsorbed onto solid carriers to form SNEGs for improved stability and enhanced flow properties. Physical characterization studies of SNEGs, in vitro release studies, and in vivo evaluation of anti-inflammatory activity of the optimized formulation were performed. All the results indicated that MLX SNEGs can be a promising alternative to conventional oral NSAIDs therapy because of enhanced dissolution characteristics and subsequent rapid onset of action.

Stability Indicating HPTLC Determination of Meloxicam.

A simple, selective, precise and stability-indicating high-performance thin layer chromatographic method of analysis of meloxicam both as a bulk drug and in formulation has been developed. The mobile phase selected was ethyl acetate:cyclohexane:glacial acetic acid (6.5:3.5:0.02% v/v/v). The calibration curve of the drug was linear in the range of 100-500 ng. The spectrodensitometric analysis was carried out in the absorbance mode at 353 nm. The mean (±RSD) values of slope, correlation coefficient and intercept were 3183.8±0.358, 0.9996±0.0321 and 13012±7.1 respectively. The system precision and the method precision studies were carried out with RSD of 0.83 and 1.89 respectively. The limit of detection and quantitation were 30 ng and 99 ng respectively. The mean percent recovery was found to be 100.3%. The method was used to analyze meloxicam from marketed tablet formulation in the presence of commonly used excipients.