9 research outputs found
Inhalable neutralizing antibodies – promising approach to combating respiratory viral infections
Monoclonal antibodies represent an exciting class of therapeutics against respiratory viral infections. Notwithstanding their specificity and affinity, the conventional parenteral administration is suboptimal in delivering antibodies for
neutralizing activity in the airways due to the poor distribution of macromolecules
to the respiratory tract. Inhaled therapy is a promising approach to overcome this
hurdle in a noninvasive manner, while advances in antibody engineering have led
to the development of unique antibody formats which exhibit properties desirable
for inhalation. In this Opinion, we examine the major challenges surrounding the
development of inhaled antibodies, identify knowledge gaps that need to be addressed and provide strategies from a drug delivery perspective to enhance the
efficacy and safety of neutralizing antibodies against respiratory viral infections
Modeling of a spray drying method to produce ciprofloxacin nanocrystals inside the liposomes utilizing a response surface methodology: Box-Behnken experimental design
Spray drying was previously used to modify the physical form of the encapsulated
ciprofloxacin drug to produce ciprofloxacin nanocrystals inside the liposomes (CNL).
The purpose of the present study was to optimize CNL powder production by
evaluating the response surface via design of experiments (DoE). Using the
Box–Behnken (BB) design, the study independent variables were the protectant type
(sucrose, trehalose or lactose), protectant amount, drying temperature, and spray gas
flow. Individual spray drying experiments were performed at various set points for each
variable followed by characterization of the produced powders. Liposomal particle size,
drug encapsulation efficiency (EE%), liposomal surface zeta potential, and nanocrystal
dimensions were the design dependant variables. By applying the least square
regression method on the experimental data, mathematical models were developed
using the mathematical software package MATLAB R2018b. Model reliability and the
significance of the model’s factors were estimated using analysis of variance (ANOVA).
The generated CNL powders showed spherical to elliptical liposomal vesicles with
particle sizes ranging from 98 to 159 nm. The EE (%) ranged from 30 to 95% w/w while
the zeta potential varied between -3.5 and -10.5 mV. The encapsulated ciprofloxacin
nanocrystals were elongated cylindrical structures with an aspect ratio of 4.0 - 7.8.
Coefficients of determination ( R 2 > 0.9) revealed a good agreement between the
predicted and experimental values for all responses except for the nanocrystal
dimensions. Sucrose and lactose were superior to trehalose in protecting the
liposomes during spray drying. The amount of sugar significantly affected the
characteristics of the CNL powders ( p -value < 0.05). In conclusion, the DoE
approach using BB design has efficiently modelled the generation of CNL by spray
drying. The optimum processing conditions which produced high drug encapsulation
(90%) after formation of nanocrystals and a vesicle size of ~125 nm utilized 57% (w/w)
sucrose, an 80°C inlet temperature, and an atomization rate of 742 L/hr
Transmucosal drug administration as an alternative route in palliative and end-of-life care during the COVID-19 pandemic.
The Coronavirus disease 2019 (COVID-19) pandemic has led to a surge in need for alternative routes of administration of drugs for end of life and palliative care, particularly in community settings. Transmucosal routes include intranasal, buccal, sublingual and rectal. They are non-invasive routes for systemic drug delivery with the possibility of self-administration, or administration by family caregivers. In addition, their ability to offer rapid onset of action with reduced first-pass metabolism make them suitable for use in palliative and end-of-life care to provide fast relief of symptoms. This is particularly important in COVID-19, as patients can deteriorate rapidly. Despite the advantages, these routes of administration face challenges including a relatively small surface area for effective drug absorption, small volume of fluid for drug dissolution and the presence of a mucus barrier, thereby limiting the number of drugs that are suitable to be delivered through the transmucosal route. In this review, the merits, challenges and limitations of each of these transmucosal routes are discussed. The goals are to provide insights into using transmucosal drug delivery to bring about the best possible symptom management for patients at the end of life, and to inspire scientists to develop new delivery systems to provide effective symptom management for this group of patients
Incident Neuropathy in HIV-Infected Patients on HAART
We determined the incidence of and risk factors for distal sensory polyneuropathy (DSP) in individuals on HAART. Sixty-one HIV-positive subjects on HAART for at least 6 months and neuropathy free were retrospectively selected. The study included subjects who had previously tolerated d-drugs without developing DSP. Neuropathy incidence over 4 years was calculated. Cox proportional hazards models were used to determine risk factors associated with incident DSP. Nineteen subjects developed DSP over a mean follow-up of 2.4 years. Subjects never treated with a d-drug developed DSP at a rate of 21 cases per 100 person-years (95% CI, 8.9–33.7). Subjects with a history of d-drug treatment but not on a d-drug at enrollment developed DSP at a rate of 17 cases per 100 person-years (95% CI, 2.1–31.8). Those on d-drug treatment developed DSP at a rate of 25 cases per 100 person-years (95% CI, 8.7–41.6). Multivariable analysis identified age [hazard ratio (HR) = 1.09; p < 0.01] and low CD4+ nadir [hazard ratio (HR) = 0.79; p = 0.03] as significant risk factors. Current or prior history of treatment with d-drug was not a significant risk factor for incident DSP in subjects who had previously tolerated d-drug treatment without developing a toxic DSP. Age and low CD4+ are risk factors for incident DSP. However, current or prior history of d-drug treatment is not a significant risk factor for incident DSP in subjects who had previously tolerated d-drug treatment without developing a toxic DSP