Chronic osteomyelitis is a challenging disease due to its serious rates of mortality and morbidity while the currently available treatment strategies are suboptimal. In contrast to the adopted systemic treatment approaches after surgical debridement in chronic osteomyelitis, local drug delivery systems are receiving great attention in the recent decades. Local drug delivery systems using special carriers have the pros of enhancing the feasibility of penetration of antimicrobial agents to bone tissues, providing sustained release and localized concentrations of the antimicrobial agents in the infected area while avoiding the systemic side effects and toxicity. Most important, the incorporation of osteoinductive and osteoconductive materials in these systems assists bones proliferation and differentiation, hence the generation of new bone materials is enhanced. Some of these systems can also provide mechanical support for the long bones during the healing process. Most important, if the local systems are designed to be injectable to the affected site and biodegradable, they will reduce the level of invasion required for implantation and can win the patients’ compliance and reduce the healing period. They will also allow multiple injections during the course of therapy to guard against the side effect of the long-term systemic therapy. The current review presents different available approaches for delivering antimicrobial agents for the treatment of osteomyelitis focusing on the recent advances in researches for local delivery of antibiotics.

Migraine attack is a troublesome physiological condition associated with throbbing, intense headache, in one half of the head. Zolmitriptan is a potent second-generation triptan, prescribed for patients with migraine attacks, with or without an aura, and cluster headaches. The absolute bioavailability of zolmitriptan is about 40% for oral administration; due to hepatic first metabolism. Nasal administration would circumvent the pre-systemic metabolism thus increasing the bioavailability of zolmitriptan. In addition, due to the presence of microvilli and high vasculature, the absorption is expected to be faster compared to oral route. However, the bioavailability of nasal administered drugs is particularly restricted by poor membrane penetration. Thus, the aim of this work is to explore the potential of novel nanovesicular fatty acid enriched structures (novasomes) for effective and enhanced nasal delivery of zolmitriptan and investigate their nose to brain targeting potential. Novasomes were prepared using nonionic surfactant, cholesterol in addition to a free fatty acid. A 2³ full factorial design was adopted to study the influence of the type of surfactant, type of free fatty acid and ratio between the free fatty acid and the surfactant on novasomes properties. The particle size, entrapment efficiency, polydispersity index, zeta potential and % zolmitriptan released after 2 h were selected as dependent variables. Novasomes were further optimized using Design Expert® software (version 7; Stat-Ease Inc., Minneapolis, MN), and an optimized formulation composed of Span® 80:Cholesterol:stearic acid (in the ratio 1:1:1) was selected. This formulation showed zolmitriptan entrapment of 92.94%, particle size of 149.9 nm, zeta potential of −55.57 mV, and released 48.43% zolmitriptan after 2 h. The optimized formulation was further examined using transmission electron microscope, which revealed non-aggregating multi-lamellar nanovesicles with narrow size distribution. DSC, XRD examination of the optimized formulation confirmed that the drug have been homogeneously dispersed throughout the novasomes in an amorphous state. In-vivo bio-distribution studies of ^99mTc radio-labeled intranasal zolmitriptan loaded novasomes were done on mice, the pharmacokinetic parameters were compared with those following administration of intravenous ^99mTc-zolmitriptan solution. Results revealed the great enhancement in zolmitriptan targeting to the brain, with drug targeting potential of about 99% following intranasal administration of novasomes compared with the intravenous drug solution. Zolmitriptan loaded novasomes administered via the nasal route may therefore constitute an advance in the management of acute migraine attacks.

The objective of this study was to develop an efficient ocular nanovesicular carrier providing a controlled delivery of Clotrimazole (CLT); a water insoluble antifungal drug. The nanovesicular carriers were formulated using Span 60 with one of the following edge activators (EA): Tween 80 (TW80), sodium cholate (SC) or sodium deoxycholate (SDC). A 3² full factorial design was used to study the effect of two independent variables, namely, the type of EA and the ratio of Span 60 to EA. The effects of these parameters on the mean particle size, entrapment efficiency (EE) and zeta potential (ZP) were investigated as dependent variables. Then, optimization was performed producing the best optimized formulation composed of SDC as an EA at the ratio of 90:10 (Span 60:EA) with an average diameter of 479.60 nm, EE of 87.92% and ZP of −33.7 mV. The optimized nanovesicular carriers appeared as spherical unilamillar vesicles with CLT in an amorphous state as evidenced by the differential scanning calorimetry study. The antifungal activity against Candida albicans compared to niosomal formulation as well as the CLT suspension was determined. CLT-loaded nanovesicular carriers displayed sustained antifungal effect over 12 h. The AUC of the optimized formulation was 3.09 times more than that of drug suspension with no sign of irritation after testing for ocular tolerance. Therefore, the present study showed the feasibility of using non-ionic surfactant nanovesicles as carrier systems for prolonged ocular delivery of CLT.

Antibiotics are often prescribed in acne treatment; however, Propionibacterium acnes and Staphylococcus epidermidis, the two of the major acne-associated bacteria, developed antibiotic resistance. Essential oils (EOs) present a natural, safe, efficacious and multifunctional alternative treatment. This study aimed to assess the potential anti-acne activity of selected seven EOs commonly used in Mediterranean folk medicine. Antimicrobial activity screening of these oils showed oregano to exhibit the strongest antimicrobial activity with minimum inhibitory concentration (MIC) of 0.34 mg/mL and minimum bactericidal concentration (MBC) of 0.67 mg/mL against P. acnes; and MIC of 0.67 mg/mL and MBC of 1.34 mg/mL against S. epidermidis. The composition of the most effective EOs (oregano and thyme) was determined using gas chromatography-mass spectrometry (GC-MS). Monoterpenoid phenols predominated oregano and thyme EO with thymol percentile 99 and 72, respectively. Thymol showed MIC 0.70 mg/mL against both P. acnes and S. epidermidis whereas MBC was 1.40 and 2.80 mg/mL against P. acnes and S. epidermidis, respectively. Moreover, oregano exhibited the strongest anti-biofilm effect against S. epidermidis with MBIC 1.34 mg/mL and killing dynamic time of 12 and 8 h against P. acnes and S. epidermidis, respectively. Oregano, the most effective EO, was formulated and tested as a nanoemulsion in an acne animal mouse model. The formulation showed superior healing and antimicrobial effects compared to the reference antibiotic. Collectively, our data suggested that oregano oil nanoemulsion is a potential natural and effective alternative for treating acne and overcoming the emerging antibiotic resistance.

Spironolactone (SL) is a US Food and Drug Administration-approved drug for the treatment of hypertension and various edematous conditions. SL has gained a lot of attention for treating androgenic alopecia due to its potent antiandrogenic properties. Recently, there has been growing interest for follicular targeting of drug molecules for treatment of hair and scalp disorders using nanocolloidal lipid-based delivery systems to minimize unnecessary systemic side effects associated with oral drug administration. Accordingly, the objective of this study is to improve SL efficiency and safety in treating alopecia through the preparation of colloidal nanostructured lipid carriers (NLCs) for follicular drug delivery. SL-loaded NLCs were prepared by an emulsion solvent diffusion and evaporation method using 2³ full factorial design. All of the prepared formulations were spherical in shape with nanometric size range (215.6–834.3 nm) and entrapment efficiency >74%. Differential scanning calorimetry thermograms and X-ray diffractograms revealed that SL exists in amorphous form within the NLC matrices. The drug release behavior from the NLCs displayed an initial burst release phase followed by sustained release of SL. Confocal laser scanning microscopy confirmed the potential of delivering the fluorolabeled NLCs within the follicles, suggesting the possibility of using SL-loaded NLCs for localized delivery of SL into the scalp hair follicles.