Drug Delivery Letters - Volume 7, Issue 2, 2017

Background: The invention of an efficacious drug delivery system for the treatment of HIV/AIDS still remains a worldwide problem and presently, an ideal remedy for HIV/AIDS is not available. One of the greatest achievements in transforming HIV infection into a chronically managed disease is anti-retroviral therapy (ART) including Highly Active Antiretroviral Therapy (HAART) which has increased the life span and improved the quality of life of the HIV/AIDS patient. But, the lack of widespread preventive measures and the inability of anti-retroviral (ARV) drugs to eliminate HIV from infected cells still remain a challenge. Also, the current ARVs are unable to reach the HIV viral load present in the brain which is one of the important sanctuary sites for the HIV virus. Objective: Thus, now is the time to explore nanotechnology and its potential in the treatment and prevention of HIV/AIDS. Particularly, nanocarriers, which are lipidic in nature, have proven to be beneficial in the case of ARV drugs. Conclusion: Lipid based ARV formulations protect the compounds from degrading and enhance the potency as well as reduce the toxicity of the drug. This review focusses on the emergence of polymeric and lipid based nanocarriers with major emphasis on lipid based drug delivery system.

Background: Advances in methods for engineering bacterial outer membrane vesicles are improving their utility as therapeutic and drug delivery agents. Specifically, bacterial vesicles have been investigated as adjuvants in vaccine formulations for some time. While success in this field has been demonstrated in animal models, especially in protection from infection by bacteria including Shigella, Acinetobacter, and Vibrio, further advances in bacterial vesicle engineering will make these materials more amenable as both vaccine components and drug delivery vehicles. Specifically, novel methods being developed to leverage natural bacterial processes in order to load specific cargo into bacterial vesicles as well as decorate their outer surface. Objective: This mini-review explores current literature focusing on research into the use of bacterial membrane vesicles in vaccine formulations as well as emerging technologies for engineering these structures, including cargo loading and surface modification. Conclusion: Engineered bacterial vesicles are emerging as novel reagents in the development of vaccines for bacterial pathogens and as adjuvant components of existing vaccine formulations. With continued advances in microbial engineering there is significant potential to develop bacterial vesicles as tools for not only vaccine development but also for use in the delivery of therapeutic compounds to targeted cells.

Background and Objective: Chitosan is a polymer widely used in the pharmaceutical industry. It is capable of interacting with sodium tripolyphosphate (TPP) forming nanoparticles (NPs) from the process of ionic gelation. This process uses factors that allow modulating the size of the NPs to be obtained. One of these factors is the incorporation of modifying agents of the ionic strength in the medium in order to obtain more stable and smaller NPs. Methods: A study of different salts was carried out. These were incorporated into the medium in concentrations that ranged between 0.05 M and 0.1 M. The characterization of NPs was performed by means of dynamic light scattering and transmission electron microscopy. Results: The salts that could decrease the size of the NPs less than 100 nm were NaCl, KCl and Na-HCO3, finally selecting NaCl as modifier agent of the ionic strength. Subsequently, the elaboration process of Chitosan NPs was optimized by means of an experimental design, being finally obtained particles with an average submicron diameter of 64.5 ± 1.8 nm, with irregular shape, smooth surface and a positive zeta potential of 32.6 ± 3.9 mV. Conclusion: In the analysis of salts it was possible to identify that only NaCl and NaHCO3 were capable of decreasing the size of chitosan NPs under 100 nm, obtaining particles of irregular shape and smooth surface.

Background and Objective: Glycyrrhetinic acid (GHA) potential has therapeutic and nutricosmetic activity. Poor aqueous solubility is the main limiting factor in usage of GHA in variety of application. The main objective of this study is to improve aqueous solubility of GHA by using various nanonization techniques. Method: GHA nanocrystals were prepared by three different top down technologies. GHA (5% w/w) was dispersed in aqueous surfactant solution [1% (w/w) Plantacare 2000 UP or Tween 80] to prepare the coarse suspension. Nanocrystals were produced by using techniques like high pressure homogenization (HPH), bead milling (BM) and combination technology (CT, BM followed by HPH). Nanocrystals were characterized for their particle size, zeta potential (ZP), agglomeration behavior and crystallinity by powder X-ray diffraction (PXRD) pattern. The long term stability of the GHA nanocrystals were assessed in three different storage conditions i.e. 4°C, 25°C and 40°C. Results: The CT process produced smallest size nanocrystal (smartCrystal®),i.e. 155 nm, compared to HPH (324 nm) and BM (268 nm). Plantacare 2000 UP had a better stabilization effect compared to Tween 80. Saturation solubility study showed particle size dependent increase in solubility. Smallest nanocrystal obtained by CT process had highest solubility followed by nanocrystals obtained by BM and HPH process. Conclusion: The selection of suitable stabilizer with optimal performance and production method are crucial for producing nanocrystals having good stability profile. Among the production methods used, CT process produced stable narrow particle size range crystals with enhanced solubility profile.

Objective: The main aim of this study was to improve bioavailability of aceclofenac using neem gum as water soluble carrier for the development of solid dispersion based dosage form of the drug. Methods: Solid dispersions (SD) of aceclofenac were prepared by solvent evaporation technique and in the form of co-grinding mixture (CGM). Four batches of neem gum based solid dispersions of aceclofenac were prepared by varying the drug polymer ratio (1:1, 1:2, 1:3 and 1:5). Prepared solid dispersions were evaluated for solubility, FTIR, DSC, X-RD, SEM and in vitro release and the optimized batch was utilized to develop solid dosage form in the form of tablet. The final dosage form (tablet of neem gum based solid dispersion) was evaluated for physicochemical characterization, in vitro release and in vivo pharmacodynamic studies. Results: Solubility studies indicated 1:3 drug to neem gum ratio for the formulation of solid dispersion of drug. CGM also indicated improved solubility of drug. FTIR studies indicated no interaction of drug to polymer (presence of characteristic peaks of drug). DSC and X-RD studies indicated transition from crystalline to amorphous state of drug. SEM images of dispersion showed change in surface characteristics of drug particles in solid dispersions as compared to pure drug (crystallinity of pure drug). In vitro release studies revealed enhanced dissolution rate in solid dispersion (SD1 to SD3) and solid dispersion based tablet (T1) as compared to 47% in case of pure drug. Results of in vivo pharmacodynamic studies indicated faster analgesic potential and efficacy of optimized solid dispersion based tablet formulation than that of pure drug and marketed formulation. Conclusion: The solubility, drug release and in vivo results suggested applicability of neem gum as a prospective carrier of poorly soluble drugs.

Background and Objectives: The objective of the study was to formulate and evaluate fast disintegrating oral film of zolmitriptan. Method: The film was prepared by solvent casting method using different polymers like Lycoat RS720, PVP K-30, and HPC in combination with other excipients. All prepared formulations were evaluated for physico-mechanical properties. Films were also evaluated for % moisture uptake, % moisture content, in vitro drug release studies and in vitro disintegration time. The optimized formulation (L1) was subjected to stability study as per the ICH guidelines at 40 ± 0.5°C/75 ± 5% RH for six months. In vivo studies were conducted on Wistar albino rats and concentration of drug in blood was analysed by HPLC. Various pharmacokinetic parameters for optimized formulation were determined and compared with reference (drug sol.). Results: On the basis of results of physico-mechanical properties and other parameters like in vitro disintegration time, the formulation L1 was selected as optimized formulation. The optimized formulation was found to be stable under the specified storage condition. The value of AUC0128;“t (ng h/ml), AUC0∞ (ng h/ml) Cmax (ng/ml), Tmax (h), Ke (h^-1), and t1/2 (h) of the optimized film formulation was found to be 727.72 ± 23.63, 777.17 ± 31.82, 353.67 ± 9.98, 0.5, 0.253 ± 0.023, and 2.74 ± 0.31 respectively, for the drug sol 559.71 ± 27.52, 585.18 ± 36.53, 280.87 ± 28.98, 0.5, 0.295 ± 0.032, and 2.34 ± 0.35, respectively. Relative bioavailability of optimized film formulation (L1) was 1.33 time than that of drug sol. In vitro-in vivo relationship between percentage drug absorbed and percentage drug released was also established. A moderate type of relationship (R²=0.897) was observed between percentage drug absorbed and percentage drug released. Conclusion: The results of present study showed that fast disintegrating oral film approach is suitable for the delivery of zolmitriptan. This formulation not only increase the bioavailability of drug but also produce the quick action for the migraine patients.

Objective: The aim of the present investigation was to carry out a comparative evaluation of skin permeation potential of microemulsion (ME) and niosome based topical gel formulations along with marketed gel products containing diclofenac sodium (DS). For ME formulation, solubility studies were done to select optimum oil, surfactant (S) and co-surfactant (CoS). Pseudoternary phase diagrams were constructed using water titration method at different S: CoS ratios to determine ME region. Niosomes were optimized for % drug entrapment using sequential optimization approach for four different factors, surfactant type, solvent ratio, S:Cholesterol ratio and drug amount (mg) at 3 levels. Optimized ME and niosomes were incorporated into carbopol gel base to obtain 1% DS carbopol gel. Both the ME gel and Niosome gel were compared with marketed diclofenac gels. Prepared ME, Noisome gels and marketed A, B and C gels (coded) were evaluated for visual appearance, pH, viscosity, spreadability, mechanical stress studies, % assay and ex vivo skin permeation and retention studies using rabbit skin. Result and Discussion: The pH, spreadability, results of mechanical stress studies and drug content were within the acceptable limits. All gels exhibited pseudoplastic behavior, ME gel showed the highest flowability. The percent drug permeations from different gels were found to be in the range of 19.35% to 57.86 % through rabbit skin over twelve hrs. Marketed gel B showed the highest permeation followed by niosomal gel and ME. However, the release of DS from niosomal gel showed more uniform drug release pattern. Also, the drug retention in the skin after 12 hrs for niosomal gel was significantly higher (44.35%, p < 0.01) followed by ME gel (32.24%, p < 0.05) compared to marketed gels. Our results suggest that the DS niosomal gel significantly enhances both skin permeation and retention and provides more uniform drug permeation through the skin compared to prepared ME and marketed gels.